蝙蝠冬眠相关的Leptin调控及白色脂肪棕样化机制研究
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摘要
哺乳动物的冬眠具有低代谢率以及低水分消耗等特征,并且跟长寿、种群低灭绝率、延迟发育等有密切关系；具有冬眠能力的哺乳动物还可以为缺血再灌注、缓冲低温损害、体温和心率的迅速恢复、抗肌肉萎缩和骨质疏松的相关研究提供动物模型,因此冬眠这一特殊生理现象一直都是学者研究的热点。本论文围绕着冬眠现象并以蝙蝠这一具有众多特殊特征的哺乳动物为模型展开研究：主要对实验室条件下非冬眠季节诱导蝙蝠进入冬眠、Leptin(瘦素)与冬眠的直接关联以及冬眠前蝙蝠存储的脂肪在其不能进入冬眠时的消耗变化等问题进行了深入研究。
自然条件下哺乳动物大都在冬季进入冬眠,因此对冬眠样品的采集以及生理现象的观察记录只能在冬季进行,这在时间上限制了对冬眠课题的研究。在本论文中,我们利用人工气候箱模拟野外冬眠环境,分别于春季、夏季与冬季成功的诱导了八只大蹄蝠(Hipposideros armiger)进入冬眠状态,并实时记录了蝙蝠的体温和心率变化数据。数据显示,当环境温度为9℃时,蝙蝠的体温能从正常状态的380C左右降低到10℃,心率从活跃时期的最高水平600多次每分钟降低到了最低6次每分钟。此外,我们将冬眠季节和非冬眠季节诱导的蝙蝠分为两组进行统计方差分析(one-way ANO VA),数据没有显著差异性(F1=2.850,P=0.102)。这说明了实验室条件下的冬眠诱导技术科学可靠,而且不受季节限制,从而打破了对冬眠现象研究的时间限制。
此前研究Leptin通过调节能量代谢、饮食摄入以及脂肪分解等方式对哺乳动物的异温性具有重要意义,且Leptin在冬眠物种上的进化速率要明显快于在非冬眠物种上的进化速率,冬眠物种合成的Leptin对脂肪的分解效率也显著高于非冬眠物种合成的,但是Leptin对于冬眠的具体调节机制尚不清楚。基于以上研究以及下丘脑在温度以及能量代谢调控上发挥的中枢作用,我们猜测答案可能存在于Leptin在下丘脑发挥作用的调节通路上。Leptin作用于下丘脑主要是通过其在下丘脑区域表达的唯一长型功能受体OB-R1来实现的。随后我们利用RNA干扰技术将anti-OB-Rl慢病毒活体微注射到大蹄蝠的下丘脑区域,实验结束后的原位杂交结果显示慢病毒介导的anti-OB-Rl shRNA成功敲减了下丘脑区域的OB-Rl表达,对主要功能区域弓状核、腹内侧核区域和背内侧核区域的敲减效率分别高达80%、86.6%和80.4%。通过实时记录冬眠诱导条件下蝙蝠的体温和心率等数据,结果表明Leptin通路被阻断的大蹄蝠不能进入冬眠状态。这直观地证明了Leptin是蝙蝠进入冬眠的必要条件,研究认为Leptin的存在可能为哺乳动物提供了一个“脂肪已存储”的冬眠信号。
哺乳动物冬眠前期会存储大量的脂肪以作为其冬眠期间的主要能量来源,从而保证冬眠动物在恶劣的寒冬季节存活下来。我们在大蹄蝠和大足鼠耳蝠(Myotis ricketti)诱导冬眠的过程中进行不定期的干扰,阻止它们进入冬眠状态。在10℃或者15℃环境条件下暴露一周之后,活跃的大蹄蝠体内的白色脂肪发生了明显的棕样化,即脂肪形态出现了棕色脂肪类似的多室多状态,UCP1和PGC-1α的表达量明显升高,最高可达对照组的750倍左右；而“慵懒”的大足鼠耳蝠体内的白色脂肪却没有明显变化。此外,与传统模型的皮下白色脂肪(sWAT)比腹腔白色脂肪(aWAT)更容易发生棕样化相反,大蹄蝠体内的aWAT却比sWAT更容易发生棕样化。这为白色脂肪棕样化的研究提供了新的模型,为治疗肥胖及肥胖相关疾病,尤其是腹腔脂肪相关疾病如脂肪肝炎、肠系膜疾病以及动脉粥样化等心血管疾病提供了更为宽广的视野。
Hibernation patterns have been extensively studied because of their relevance to longevity, low extinction rate, delayed development, low metabolic rate, and low water loss, resistance to muscle atrophy and osteoporosis. We studied mammal hibernation in this article, especially focused on inducing Hipposideros armiger into hibernation under laboratory condition during non-hibernation season, the regulatory mechanism of Leptin conducted on hibernation and cold-induced white adipose tissue browning using bat as a model.
Natural conditions restrict hibernation studies because sampling could only be conducted during winter, which hinders development in hibernation research. In the present study, we induced eight Great Roundleaf bats(Hipposideros armiger) into hibernation in winter, spring, and summer under laboratory conditions. Body temperature and heart rate were recorded as index parameters of hibernation. All bats entered a state of hibernation. Body temperature decreased from the normal38℃to10℃, and heart rate decreased from the highest at600beats per min to the lowest at6beats per min when the bats were placed inside the artificial climate incubator with ambient temperature of9℃. In addition, no significant difference in heart rate of torpid bats during the hibernation season and non-hibernation season (spring and summer) was observed (F1=2.850, P=0.102). In summary, hibernation in bats could be induced outside the hibernation season, which provides significant convenience for further research on hibernation in this species.
Previous studies have shown that the hormone Leptin has a key function in mammalian heterothermy by regulating metabolism and food intake via lipolysis, as well as selected pressure, which results in the increase in Leptin lipolysis activity in mammals. However, the mechanism by which Leptin functions in heterothermic regulation in mammals is unknown. By combining previous results, we speculated that the answer may lie in the Leptin signaling pathway in the hypothalamus. OB-R1(Leptin receptor long form) is mainly distributed in the hypothalamus, and has a key function in mediating Leptin function, In this study, we used OB-R1as a molecular marker to explore the mechanisms of Leptin in heterothermic regulation. We used RNA interference technology and physiological/molecular analyses with Hipposideros armiger as an animal model. Results of in situ hybridization proved that anti-OB-R1shRNA lentivirus could significantly decreased OB-R1expression in the hypothalamus, especially in the arcuate nucleus, ventromedial hypothalamic nucleus and dorsomedial nucleus. Physiological analysis demonstrated that the thermological ability of bats (e.g., low core body temperature and heart rate) was significantly depressed after OB-RL gene silencing in the hypothalamus. Thus, animals could not enter a state of hibernation. Our study first proved that Leptin pathway blocking via OB-R1silencing inhibited heterothermic regulation. Leptin may be provided a signal of "fat were enough" for inducing mammals into hibernation.
We described two species-Hipposideros armiger and Myotis ricketti, belonged to the second largest group model to study cold-induced response in morphology and molecular expression in WAT and BAT. After Exposed to10℃or15℃for7days, Harmiger showed an obvious change in morphology, with increasing multilocular adipocytes and vascular density, and the remarkably high expression of UCP1and PGC-1α in WAT, but that did not happen in M.ricketti. What is more, it was contrary to what happened in mice, the abdominal adipose tissue showed a rapid and significant browning compared to the subcutaneous adipose tissue in H.armiger. These data offer a novel strategy to research the abdominal adipose tissue for disease, such as steatohepatitis, mesenteric diseases and atheroma, as well as an unusual insight into exploration applications on human beings based on the study of this H.armiger model.
自然条件下哺乳动物大都在冬季进入冬眠,因此对冬眠样品的采集以及生理现象的观察记录只能在冬季进行,这在时间上限制了对冬眠课题的研究。在本论文中,我们利用人工气候箱模拟野外冬眠环境,分别于春季、夏季与冬季成功的诱导了八只大蹄蝠(Hipposideros armiger)进入冬眠状态,并实时记录了蝙蝠的体温和心率变化数据。数据显示,当环境温度为9℃时,蝙蝠的体温能从正常状态的380C左右降低到10℃,心率从活跃时期的最高水平600多次每分钟降低到了最低6次每分钟。此外,我们将冬眠季节和非冬眠季节诱导的蝙蝠分为两组进行统计方差分析(one-way ANO VA),数据没有显著差异性(F1=2.850,P=0.102)。这说明了实验室条件下的冬眠诱导技术科学可靠,而且不受季节限制,从而打破了对冬眠现象研究的时间限制。
此前研究Leptin通过调节能量代谢、饮食摄入以及脂肪分解等方式对哺乳动物的异温性具有重要意义,且Leptin在冬眠物种上的进化速率要明显快于在非冬眠物种上的进化速率,冬眠物种合成的Leptin对脂肪的分解效率也显著高于非冬眠物种合成的,但是Leptin对于冬眠的具体调节机制尚不清楚。基于以上研究以及下丘脑在温度以及能量代谢调控上发挥的中枢作用,我们猜测答案可能存在于Leptin在下丘脑发挥作用的调节通路上。Leptin作用于下丘脑主要是通过其在下丘脑区域表达的唯一长型功能受体OB-R1来实现的。随后我们利用RNA干扰技术将anti-OB-Rl慢病毒活体微注射到大蹄蝠的下丘脑区域,实验结束后的原位杂交结果显示慢病毒介导的anti-OB-Rl shRNA成功敲减了下丘脑区域的OB-Rl表达,对主要功能区域弓状核、腹内侧核区域和背内侧核区域的敲减效率分别高达80%、86.6%和80.4%。通过实时记录冬眠诱导条件下蝙蝠的体温和心率等数据,结果表明Leptin通路被阻断的大蹄蝠不能进入冬眠状态。这直观地证明了Leptin是蝙蝠进入冬眠的必要条件,研究认为Leptin的存在可能为哺乳动物提供了一个“脂肪已存储”的冬眠信号。
哺乳动物冬眠前期会存储大量的脂肪以作为其冬眠期间的主要能量来源,从而保证冬眠动物在恶劣的寒冬季节存活下来。我们在大蹄蝠和大足鼠耳蝠(Myotis ricketti)诱导冬眠的过程中进行不定期的干扰,阻止它们进入冬眠状态。在10℃或者15℃环境条件下暴露一周之后,活跃的大蹄蝠体内的白色脂肪发生了明显的棕样化,即脂肪形态出现了棕色脂肪类似的多室多状态,UCP1和PGC-1α的表达量明显升高,最高可达对照组的750倍左右；而“慵懒”的大足鼠耳蝠体内的白色脂肪却没有明显变化。此外,与传统模型的皮下白色脂肪(sWAT)比腹腔白色脂肪(aWAT)更容易发生棕样化相反,大蹄蝠体内的aWAT却比sWAT更容易发生棕样化。这为白色脂肪棕样化的研究提供了新的模型,为治疗肥胖及肥胖相关疾病,尤其是腹腔脂肪相关疾病如脂肪肝炎、肠系膜疾病以及动脉粥样化等心血管疾病提供了更为宽广的视野。
Hibernation patterns have been extensively studied because of their relevance to longevity, low extinction rate, delayed development, low metabolic rate, and low water loss, resistance to muscle atrophy and osteoporosis. We studied mammal hibernation in this article, especially focused on inducing Hipposideros armiger into hibernation under laboratory condition during non-hibernation season, the regulatory mechanism of Leptin conducted on hibernation and cold-induced white adipose tissue browning using bat as a model.
Natural conditions restrict hibernation studies because sampling could only be conducted during winter, which hinders development in hibernation research. In the present study, we induced eight Great Roundleaf bats(Hipposideros armiger) into hibernation in winter, spring, and summer under laboratory conditions. Body temperature and heart rate were recorded as index parameters of hibernation. All bats entered a state of hibernation. Body temperature decreased from the normal38℃to10℃, and heart rate decreased from the highest at600beats per min to the lowest at6beats per min when the bats were placed inside the artificial climate incubator with ambient temperature of9℃. In addition, no significant difference in heart rate of torpid bats during the hibernation season and non-hibernation season (spring and summer) was observed (F1=2.850, P=0.102). In summary, hibernation in bats could be induced outside the hibernation season, which provides significant convenience for further research on hibernation in this species.
Previous studies have shown that the hormone Leptin has a key function in mammalian heterothermy by regulating metabolism and food intake via lipolysis, as well as selected pressure, which results in the increase in Leptin lipolysis activity in mammals. However, the mechanism by which Leptin functions in heterothermic regulation in mammals is unknown. By combining previous results, we speculated that the answer may lie in the Leptin signaling pathway in the hypothalamus. OB-R1(Leptin receptor long form) is mainly distributed in the hypothalamus, and has a key function in mediating Leptin function, In this study, we used OB-R1as a molecular marker to explore the mechanisms of Leptin in heterothermic regulation. We used RNA interference technology and physiological/molecular analyses with Hipposideros armiger as an animal model. Results of in situ hybridization proved that anti-OB-R1shRNA lentivirus could significantly decreased OB-R1expression in the hypothalamus, especially in the arcuate nucleus, ventromedial hypothalamic nucleus and dorsomedial nucleus. Physiological analysis demonstrated that the thermological ability of bats (e.g., low core body temperature and heart rate) was significantly depressed after OB-RL gene silencing in the hypothalamus. Thus, animals could not enter a state of hibernation. Our study first proved that Leptin pathway blocking via OB-R1silencing inhibited heterothermic regulation. Leptin may be provided a signal of "fat were enough" for inducing mammals into hibernation.
We described two species-Hipposideros armiger and Myotis ricketti, belonged to the second largest group model to study cold-induced response in morphology and molecular expression in WAT and BAT. After Exposed to10℃or15℃for7days, Harmiger showed an obvious change in morphology, with increasing multilocular adipocytes and vascular density, and the remarkably high expression of UCP1and PGC-1α in WAT, but that did not happen in M.ricketti. What is more, it was contrary to what happened in mice, the abdominal adipose tissue showed a rapid and significant browning compared to the subcutaneous adipose tissue in H.armiger. These data offer a novel strategy to research the abdominal adipose tissue for disease, such as steatohepatitis, mesenteric diseases and atheroma, as well as an unusual insight into exploration applications on human beings based on the study of this H.armiger model.
引文
Abbas-Terki T, W Blanco-Bose, N Deglon, W Pralong, P Aebischer.2002. Lentiviral-mediated rna interference. Hum Gene Ther 13:2197-2201.
Ahima RS, SY Osei.2004. Leptin signaling. Physiol Behav 81:223-241.
Akasaka Y, M Tsunoda, T Ogata, T Ide, K Murakami.2010. Direct evidence for leptin-induced lipid oxidation independent of long-form leptin receptor. Biochim Biophys Acta 1801:1115-1122.
Alessi M, F Peiretti, P Morange, M Henry, G Nalbone, I Juhan-Vague.1997. Production of plasminogen activator inhibitor by human adipose tissue: Possible link between visceral fat accumulation and vascular disease. Diabetes 46:860-867.
Alexopoulos N, D Katritsis, P Raggi.2014. Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis. Atherosclerosis. In press.
Andrews MT.2004. Genes controlling the metabolic switch in hibernating mammals. Biochem Soc Trans 32:1021-1024.
Anufriev A, T Solomonova, G Arkhipov, A Turpanov, N Solomonov.2003. Bat (vespertilionidae) hibernation in the northeastemmost part of their geographic range. Dokl Bio Sci 392:413-415.
Ashrafi K, FY Chang, JL Watts, AG Fraser, RS Kamath, J Ahringer et al.2003. Genome-wide rnai analysis of caenorhabditis elegans fat regulatory genes. Nature 421:268-272.
Audet D, MB Fenton.1988. Heterothermy and the use of torpor by the bat eptesicus fuscus (chiroptera:Vespertilionidae):A field study. Physiol Zool 61:197-204.
Audet D, DW Thomas.1996. Evaluation of the accuracy of body temperature measurement using external radio transmitters. Can J Zoolog 74:1778-1781.
Bai Y, S Zhang, K-S Kim, J-K Lee, K-H Kim.1996. Obese gene expression alters the ability of 30A5 preadipocytes to respond to lipogenic hormones. J Biol Chem 271:13939-13942.
Banks WA, SA Farr, JE Morley.2006. The effects of high fat diets on the blood-brain barrier transport of leptin:Failure or adaptation? Physiol Behav 88:244-248.
Barbatelli G, I Murano, L Madsen, Q Hao, M Jimenez, K Kristiansen et al.2010. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol-Endoc M 298:1244-1253.
Barnes BM.1989. Freeze avoidance in a mammal:Body temperatures below 0℃ in an arctic hibernator. Science 244:1593-1595.
Bartelt A, J Heeren.2014. Adipose tissue browning and metabolic health. Nat Rev Endocrinol 10:24-36.
Bartholomew GA, TJ Cade.1957. Temperature regulation, hibernation, and aestivation in the little pocket mouse, perognathus longimembris. J Mammal 38:60-72.
Bostrom P, J Wu, MP Jedrychowski, A Korde, L Ye, JC Lo et al.2012. A pgc-1α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481:463-468.
Bouret SG, SH Bates, S Chen, MG Myers, Jr., RB Simerly.2012. Distinct roles for specific leptin receptor signals in the development of hypothalamic feeding circuits. J Neurosci 32:1244-1252.
Bowlin MS, M Wikelski.2008. Pointed wings, low wingloading and calm air reduce migratory flight costs in songbirds. PLoS One 3:e2154.
Brack Jr V, JW Twente.1985. The duration of the period of hibernation of three species of vespertilionid bats. I. Field studies. Can J Zoolog 63:2952-2954.
Bray G.2003. Obesity is a chronic, relapsing neurochemical disease. Int J Obesity 28: 34-38.
Bray GA.2006. Obesity:The disease. J Med Chem 49:4001-4007.
Bray GA, LA Tartaglia.2000. Medicinal strategies in the treatment of obesity. Nature 404:672-677.
Campfield LA, FJ Smith, Y Guisez, R Devos, P Burn.1995. Recombinant mouse ob protein:Evidence for a peripheral signal linking adiposity and central neural networks. Science 269:546-549.
Cannon B, J Nedergaard.2004. Brown adipose tissue:Function and physiological significance. Physiol Rev 84:277-359.
Cannon B, J Nedergaard.2012. Neither brown nor white. Nature 488:286-287.
Carey HV, MT Andrews, SL Martin.2003. Mammalian hibernation:Cellular and molecular responses to depressed metabolism and low temperature. Physiol Rev 83:1153-1181.
Catalanotto C, G Azzalin, G Macino, C Cogoni.2000. Gene silencing in worms and fungi. Nature 404:245-245.
Chehab FF, K Mounzih, R Lu, ME Lim.1997. Early onset of reproductive function in normal female mice treated with leptin. Science 275:88-90.
Chen H, O Charlat, LA Tartaglia, EA Woolf, X Weng, SJ Ellis et al.1996. Evidence that the diabetes gene encodes the leptin receptor:Identification of a mutation in the leptin receptor gene in db/db mice. Cell 84:491-495.
Chen Q, T Zhu, G Jones, J Zhang, Y Sun.2013. First knockdown gene expression in bat (Hipposideros armiger) brain mediated by lentivirus. Mol Biotechnol 54: 564-571.
Cheng H-C, L-L Lee.2004. Temporal variations in the size and composition of formosan leaf-nosed bat(Hipposideros terasensis) colonies in central taiwan. Zool Stud 43:787-794.
Cinti S.2001. The adipose organ:Morphological perspectives of adipose tissues. P Nutr Soc.60:319-328.
Concannon P, K Levac, R Rawson, B Tennant, A Bensadoun.2001. Seasonal changes in serum leptin, food intake, and body weight in photoentrained woodchucks. Am J Physiol Regul Integr Comp Physiol 281:951-959.
Considine RV, MK Sinha, ML Heiman, A Kriauciunas, TW Stephens, MR Nyce et al. 1996. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292-295.
Cotton C, H Harlow.1995. Fasting biochemistry of representative spontaneous and facultative hibernators:The white-tailed prairie dog and the black-tailed prairie dog. Physiol Zoolog 68:915-934.
Cypess AM, S Lehman, G Williams, I Tal, D Rodman, AB Goldfine et al.2009. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360:1509-1517.
Daan S.1972. Activity during natural hibernation in three species of vespertilionid bats. Neth J Zoo123:1-71.
Daan S, BM Barnes, AM Strijkstra.1991. Warming up for sleep? Ground squirrels sleep during arousals from hibernation. Neurosci Lett 128:265-268.
Dalamaga M, SH Chou, K Shields, P Papageorgiou, SA Polyzos, CS Mantzoros.2013. Leptin at the intersection of neuroendocrinology and metabolism:Current evidence and therapeutic perspectives. Cell Metab 18:29-42.
Dausmann KH.2005. Measuring body temperature in the field—evaluation of external vs. Implanted transmitters in a small mammal. J Therm Biol 30:195-202.
Davis DE, RH Swade.1983. Circannual rhythm of torpor and molt in the ground squirrel, Spermophilus beecheyi. Comp Bioche Phys A 76:183-187.
De Vos P, M Guerre-Millot, A Leturque, J Girard, B Staels, J Auwerx.1995. Transient increase in obese gene expression after food intake or insulin administration. Nature 377:527-528
Domanski MJ, KA Jablonski, MM Rice, SE Fowler, E Braunwald.2006. Obesity and cardiovascular events in patients with established coronary disease. Eur Heart J 27:1416-1422.
Drew KL, CL Buck, BM Barnes, SL Christian, BT Rasley, MB Harris.2007. Central nervous system regulation of mammalian hibernation:Implications for metabolic suppression and ischemia tolerance. J Neurochem 102:1713-1726.
Du T, X Sun, P Yin, R Huo, C Ni, X Yu.2013. Increasing trends in central obesity among Chinese adults with normal body mass index,1993-2009. BMC Public Health 13:327.
Dunbar MB, TE Tomasi.2006. Arousal patterns, metabolic rate, and an energy budget of eastern red bats (lasiurus borealis) in winter. J Mammal 87:1096-1102.
Ewing WG, EH Studier, MJ OTarrell.1970. Autumn fat deposition and gross body composition in three species of myotis. Comp Biochem Physiol 36:119-129.
Finkelstein EA, IC Fiebelkorn, G Wang.2003. National medical spending attributable to overweight and obesity:How much, and who's paying? Health Affair 22: 219-226.
Fleming TH, P Eby, T Kunz, M Fenton.2003. Ecology of bat migration. Bat ecology. 156-208.
Florant GL.1998. Lipid metabolism in hibernators:The importance of essential fatty acids. Am Zool 38:331-340.
Fruhbeck G, M Aguado, JA Martinez.1997. In vitro lipolytic effect of leptin on mouse adipocytes:Evidence for a possible autocrine/paracrine role of leptin. Biochem Bioph Res Co 240:590-594.
Freeman DA, DA Lewis, AS Kauffinan, RM Blum, J Dark.2004. Reduced leptin concentrations are permissive for display of torpor in Siberian hamsters. Am J of Physiol-Reg 1287:R97-R103.
French AR.1985. Allometries of the durations of torpid and euthermic intervals during mammalian hibernation:Atest of the theory of metabolic control of the timing of changes in body temperature. J Comp Physiol B 156:13-19.
Frerichs KU.1999. Neuroprotective strategies in nature—novel clues for the treatment of stroke and trauma. Acta Neurochir Suppl 73:57-61.
Frerichs KU, JM Hallenbeck.1998. Hibernation in ground squirrels induces state and species-specific tolerance to hypoxia and aglycemia:An in vitro study in hippocampal slices. J Cereb Blood Flow Metab 18:168-175.
Gainsford T, TA Willson, D Metcalf, E Handman, C McFarlane, A Ng et al.1996. Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. P Natl A Sci 93:14564-14568.
Geiser F.1988. Reduction of metabolism during hibernation and daily torpor in mammals and birds:Temperature effect or physiological inhibition? J Comp Physiol B 158:25-37.
Geiser F.2004. Metabolic rate and body temperature reduction during hibernation and daily torpor. Annu Rev Physiol 66:239-274.
Geiser F.2013. Hibernation. Curr Biol 23:R188-R193.
Geiser F, RM Brigham.2012. The other functions of torpor. Living in a seasonal world. 109-121.
Geiser F, C Turbill.2009. Hibernation and daily torpor minimize mammalian extinctions. Naturwissenschaften 96:1235-1240.
Golden PL, TJ Maccagnan, WM Pardridge.1997. Human blood-brain barrier leptin receptor. Binding and endocytosis in isolated human brain microvessels. J Clin Invest 99:14-18.
Grunfeld C, C Zhao, J Fuller, A Pollack, A Moser, J Friedman et al.1996. Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. J Clin Invest 97:2152-2157.
Gunnell GF, NB Simmons.2005. Fossil evidence and the origin of bats. J Mamm Evol 12:209-246.
Halaas JL, KS Gajiwala, M Maffei, SL Cohen, BT Chait, D Rabinowitz et al.1995. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543-546.
Halsall AL, JG Boyles, JO Whitaker.2012. Body temperature patterns of big brown bats during winter in a building hibernaculum. J Mammal 93:497-503.
Harms M, P Seale.2013. Brown and beige fat:Development, function and therapeutic potential. Nat Med 19:1252-1263.
Harris MB, WK Milsom.1995. Parasympathetic influence on heart rate in euthermic and hibernating ground squirrels. J Exp Biol 198:931-937.
He L, Y Pan, G He, B Lin, CC Liao, X Zuo et al.2010. Structural and functional studies of leptins from hibernating and non-hibernating bats. Gen Comp Endocrinol 168:29-35.
Heldmaier G, T Ruf.1992. Body temperature and metabolic rate during natural hypothermia in endotherms. J Comp Physiol B 162:696-706.
Henson MC, VD Castracane.2000. Leptin in pregnancy. Biol Reprod 63:1219-1228.
Hiebert SM, EM Thomas, TM Lee, KM Pelz, SM Yellon, I Zucker.2000. Photic entrainment of circannual rhythms in golden-mantled ground squirrels:Role of the pineal gland. J Biol Rhythm 15:126-134.
Hileman SM, J Torn(?)e, JS Flier, C Bjorbaek.2000. Transcellular transport of leptin by the short leptin receptor isoform obra in madin-darby canine kidney cells 1. Endocrinology 141:1955-1961.
Hill JE, JD Smith.1984. Bats:A natural history. Cambridge University Press.
Ho Y-Y, L-L Lee.2003. Roost selection by formosan leaf-nosed bats (Hipposideros armiger terasensis). Zool Sci 20:1017-1024.
Hock RJ.1951. The metabolic rates and body temperatures of bats. Biol Bull 101:289-299.
Hoffman RA, PF Robinson, H Magalhaes.1968. The golden hamster:Its biology and use in medical research. The Iowa State University Press.
Holland RA, DA Waters.2005. Echolocation signals and pinnae movement in the fruitbat rousettus aegyptiacus. Acta Chiropterol 7:83-90.
Holland RA, DA Waters, JM Rayner.2004. Echolocation signal structure in the megachiropteran bat rousettus aegyptiacus geoffroy 1810. J Exp Biol 207: 4361-4369.
Hope PR, G Jones.2012. Warming up for dinner:Torpor and arousal in hibernating natterer's bats (Myotis nattereri) studied by radio telemetry. J Comp Physiol B 182:569-578.
Hubert HB, M Feinleib, PM McNamara, WP Castelli.1983. Obesity as an independent risk factor for cardiovascular disease:A 26-year follow-up of participants in the framingham heart study. Circulation 67:968-977.
Jepsen GL.1966. Early eocene bat from wyoming. Science 154:1333-1339.
Jespersen NZ, TJ Larsen, L Peijs, S Daugaard, P Hom(?)e, A Loft et al.2013. A classical brown adipose tissue mrna signature partly overlaps with brite in the supraclavicular region of adult humans. Cell Metab 17:798-805.
Jia W, K Xiang, L Chen, J Lu, Y Wu.2002. Epidemiological study on obesity and its comorbidities in urban Chinese older than 20 years of age in shanghai, china. ObesRev 3:157-165.
Johnson JS, MJ Lacki, SC Thomas, JF Grider.2012. Frequent arousals from winter torpor in rafinesque's big-eared bat (Corynorhinus rafinesquii). PLoS One 7: e49754.
Jonasson KA, CK Willis.2011. Changes in body condition of hibernating bats support the thrifty female hypothesis and predict consequences for populations with white-nose syndrome. P1oS one 6:e21061.
Jones KE, A Purvis, A Maclarnon, OR BININDA-EMONDS, NB Simmons.2002. A phylogenetic supertree of the bats (mammalia:Chiroptera). Biol Rev 77: 223-259.
Kortner G, F Geiser.2000. Torpor and activity patterns in free-ranging sugar gliders petaurus breviceps (marsupialia). Oecologia 123:350-357.
Kafri T, U Blomer, DA Peterson, FH Gage, IM Verma.1997. Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors. Nat Genet 17:314-317.
Kallen F.1977. The cardiovascular system of bats:Structure and function. Biol Bat 3: 289-483.
Katsuura G, A Asakawa, A Inui.2002. Roles of pancreatic polypeptide in regulation of food intake. Peptides 23:323-329.
Konturek P, J Konturek, M Czesnikiewicz-Guzik, T Brzozowski, E Sito, S Konturek. 2005. Neuro-hormonal control of food intake:Basic mechanisms and clinical implications. J Physiol Pharmacol 56:5-25.
Kowalski TJ, S-M Liu, RL Leibel, SC Chua.2001. Transgenic complementation of leptin-receptor deficiency i. Rescue of the obesity/diabetes phenotype of lepr-null mice expressing a lepr-b transgene. Diabetes 50:425-435.
Kronfeld-Schor N, C Richardson, BA Silvia, TH Kunz, EP Widmaier.2000. Dissociation of leptin secretion and adiposity during prehibernatory fattening in little brown bats. Am J Physiol Regul Integr Comp Physiol 279:1277-1281.
Kulzer E.1967. Die herztatigkeit bei lethargischen und winterschlafenden fledermausen. Z Vergl Physiol 56:63-94.
Kunz TH, MB Fenton.2006. Bat ecology. University of Chicago Press.
Kunz TH, JA Wrazen, C Burnett.1998. Changes in body mass and fat reserves in pre-hibernating little brown bats (Myotis lucifugus). Ecoscience 5:8-17.
Ladyman SR, DR Grattan.2005. Suppression of leptin receptor messenger ribonucleic acid and leptin responsiveness in the ventromedial nucleus of the hypothalamus during pregnancy in the rat. Endocrinology 146:3868-3874.
Lee K, JY Park, W Yoo, T Gwag, JW Lee, MW Byun et al.2008. Overcoming muscle atrophy in a hibernating mammal despite prolonged disuse in dormancy: Proteomic and molecular assessment. J Cell Biochem 104:642-656.
Lee M, I Choi, K Park.2002. Activation of stress signaling molecules in bat brain during arousal from hibernation. J Neurochem 82:867-873.
Lementowski PW, SB Zelicof.2008. Obesity and osteoarthritis. Am J Orthop 37:148-151.
Li W, Z Shi, M Yu, W Ren, C Smith, JH Epstein et al.2005. Bats are natural reservoirs of sars-like coronaviruses. Science 310:676-679.
Lidell ME, MJ Betz, OD Leinhard, M Heglind, L Elander, M Slawik et al.2013. Evidence for two types of brown adipose tissue in humans. Nat Med 19:631-634.
Lim S, J Honek, Y Xue, T Seki, Z Cao, P Andersson et al.2012. Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice. Nat Protoc 7:606-615.
Liu JN, WH Karasov.2011 Hibernation in warm hibernacula by free-ranging formosan leaf-nosed bats (Hipposideros terasensis) in subtropical taiwan. J Comp Physio1B181:125-135.
Livak KJ, TD Schmittgen.2001. Analysis of relative gene expression data using real-time quantitative per and the 2-△△ct method. Methods 25:402-408.
Lyman C, P Chatfield.1955. Physiology of hibernation in mammals. Physiol Rev 35: 403-425.
Lyman C, J Willis, A Malan, L Wang.1982. Hibernation and torpor in mammals and birds. New York Academic Press.
Margetic S, C Gazzola, G Pegg, R Hill.2002. Leptin:A review of its peripheral actions and interactions. Int J Obesity 26:1407-1433.
McGee-Lawrence ME, HV Carey, SW Donahue.2008. Mammalian hibernation as a model of disuse osteoporosis:The effects of physical inactivity on bone metabolism, structure, and strength. Am J Physiol-Reg I 295:1999-2014.
Menaker M.1964. Frequency of spontaneous arousal from hibernation in bats. Nature 203:540-541.
Mercer JG, N Hoggard, LM Williams, CB Lawrence, LT Hannah, P Trayhurn.1996. Localization of leptin receptor mrna and the long form splice variant (ob-rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Lett 387:113-116.
Messier SP.2009. Obesity and osteoarthritis:Disease genesis and nonpharmacologic weight management. Med Clin N Am 93:145-159.
Muoio DM, GL Dohn, FT Fiedorek, EB Tapscott, RA Coleman.1997. Leptin directly alters lipid partitioning in skeletal muscle. Diabetes 46:1360-1363.
Nedergaard J, B Cannon.2013. Ucpl mRNA does not produce heat. BBA-Mol Cell BiolL 1831:943-949.
Ollivier F, D Samuelson, D Brooks, P Lewis, M Kallberg, A Komaromy.2004. Comparative morphology of the tapetum lucidum (among selected species). Vet Ophthalmol 7:11-22.
Organization WH.1997. Preventing and managing the global epidemic-report of a who consultation on obesity. Geneva, World Health Organization.
Organization WH.2000. Obesity:Preventing and managing the global epidemic. Geneva, World Health Organization.
Organization WH.2010. Obesity and overweight:Fact sheet no.311. Geneva, World Health Organization.
Ormseth OA, M Nicolson, MA Pelleymounter, BB Boyer.1996. Leptin inhibits prehibernation hyperphagia and reduces body weight in arctic ground squirrels. Am J Physiol 271:1775-1779.
Otero M, Ro Lago, F Lago, FF Casanueva, C Dieguez, JJ Gomez-Reino et al.2005. Leptin, from fat to inflammation:Old questions and new insights. FEBS letters 579:295-301.
Pakhotin PI, ID Pakhotina, AB Belousov.1993. The study of brain slices from hibernating mammals in vitro and some approaches to the analysis of hibernation problems in vivo. Prog Neurobiol 40:123-161.
Pan Y-H, Y Zhang, J Cui, Y Liu, BM McAllan, C-C Liao et al.2013. Adaptation of phenylalanine and tyrosine catabolic pathway to hibernation in bats. P1oS one 8:e62039.
Park KJ, G Jones, RD Ransome.2000. Torpor, arousal and activity of hibernating greater horseshoe bats (Rhinolophusferrumequinum). Funct Ecol 14:580-588.
Patterson BD, MR Willig, RD Stevens.2003. Trophic strategies, niche partitioning, and patterns of ecological organization. Bat Ecol 9:536-557.
Paxinos G.2004. The mouse brain in stereotaxic coordinates. Gulf Professional Publishing.
Pelleymounter MA, MJ Cullen, MB Baker, R Hecht, D Winters, T Boone et al.1995. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540-543.
Pengelley E, SJ Asmundson, B Barnes, RC Aloia.1976. Relationship of light intensity and photoperiod to circannual rhythmicity in the hibernating ground squirrel, citellus lateralis. Comp Biochem Phys A 53:273-277.
Pereira MJR, H Rebelo, EC Teeling, SJ O'Brien, I Mackie, SSH Bu et al.2006. Status of the world's smallest mammal, the bumble-bee bat (craseonycteris thonglongyai) in myanmar. Oryx 40:456-463.
Petrovic N, TB Walden, IG Shabalina, JA Timmons, B Cannon, J Nedergaard.2010. Chronic peroxisome proliferator-activated receptor y (ppary) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, ucpl-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem 285:7153-7164.
Prendergast BJ, DA Freeman, I Zucker, RJ Nelson.2002. Periodic arousal from hibernation is necessary for initiation of immune responses in ground squirrels. Am J Physiol-Reg I 282:1054-1062.
Qian H, GJ Hausman, MM Compton, MJ Azain, DL Hartzell, CA Baile.1998. Leptin regulation of peroxisome proliferator-activated receptor-y, tumor necrosis factor, and uncoupling protein-2 expression in adipose tissues. Biochem Bioph Res Co 246:660-667.
Reidy SP, J-M Weber.2000. Leptin:An essential regulator of lipid metabolism. Comp Biochem Phys A 125:285-298.
Reite OB, WH Davis.1966. Thermoregulation in bats exposed to low ambient temperatureis. Exper Biol Med 121:1212-1215.
Resnick HE, P Valsania, JB Halter, X Lin.2000. Relation of weight gain and weight loss on subsequent diabetes risk in overweight adults. J Epidemiol Commun H 54:596-602.
Roignant JY, C Carre, B Mugat, D Szymczak, JA Lepesant, C Antoniewski.2003. Absence of transitive and systemic pathways allows cell-specific and isoform-specific rnai in drosophila. Rna 9:299-308.
Rosell M, M Kaforou, A Frontini, A Okolo, Y-W Chan, E Nikolopoulou et al.2014. Brown and white adipose tissues. Intrinsic differences in gene expression and response to cold exposure in mice. Am J Physiol-Endoc M. In Press.
Rosen ED, BM Spiegelman.2006. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 444:847-853.
Rousseau K, Z Atcha, A Loudon.2003. Leptin and seasonal mammals. J Neuroendocrinol 15:409-414.
Saad MF, A Khan, A Sharma, R Michael, MG Riad-Gabriel, R Boyadjian et al.1998. Physiological insulinemia acutely modulates plasma leptin. Diabetes 47:544-549.
Sarmiento U, B Benson, S Kaufman, L Ross, M Qi, S Scully et al.1997. Morphologic and molecular changes induced by recombinant human leptin in the white and brown adipose tissues of C57 BL/6 mice. Lab Invest 77:243-256.
Sarraf P, RC Frederich, EM Turner, G Ma, NT Jaskowiak, DJ Rivet et al.1997. Multiple cytokines and acute inflammation raise mouse leptin levels:Potential role in inflammatory anorexia. J Exp Med 185:171-176.
Schaffler A, J Scholmerich, C Buchler.2005. Mechanisms of disease:Adipocytokines and visceral adipose tissue-emerging role in nonalcoholic fatty liver disease. Nat Clin Pract Gastr 2:273-280.
Schaffhauser A, A Stricker-Krongrad, L Brunner, F Cumin, C Gerald, S Whitebread et al.1997. Inhibition of food intake by neuropeptide Y Y5 receptor antisense oligodeoxynucleotides. Diabetes 46:1792-1798.
Schulz TJ, TL Huang, TT Tran, H Zhang, KL Townsend, JL Shadrach et al.2011. Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat. P Natl A Sci 108:143-148.
Schwartz MW, SC Woods, D Porte, RJ Seeley, DG Baskin.2000. Central nervous system control of food intake. Nature 404:661-671.
Seale P, B Bjork, W Yang, S Kajimura, S Chin, S Kuang et al.2008. Prdml6 controls a brown fat/skeletal muscle switch. Nature 454:961-967.
Shigemura N, H Miura, Y Kusakabe, A Hino, Y Ninomiya.2003. Expression of leptin receptor (ob-r) isoforms and signal transducers and activators of transcription (stats) mrnas in the mouse taste buds. Arch Histol Cytol 66:253-260.
Shore AM, A Karamitri, P Kemp, JR Speakman, NS Graham, MA Lomax.2013. Cold-induced changes in gene expression in brown adipose tissue, white adipose tissue and liver. P1oS one 8:e68933.
Siegrist-Kaiser CA, V Pauli, CE Juge-Aubry, O Boss, A Pernin, WW Chin et al.1997. Direct effects of leptin on brown and white adipose tissue. J Clin Invest 100: 2858-2864.
Sierra-Honigmann MR, AK Nath, C Murakami, G Garcia-Cardena, A Papapetropoulos, WC Sessa et al.1998. Biological action of leptin as an angiogenic factor. Science 281:1683-1686.
Simmons NB, JH Geisler.1998. Phylogenetic relationships of icaronycteris, archaeonycteris, hassianycteris, and palaeochiropteryx to extant bat lineages, with comments on the evolution of echolocation and foraging strategies in microchiroptera. B Am Mus Nat Hist no.235.
Simmons NB, KL Seymour, J Habersetzer, GF Gunnell.2008. Primitive early eocene bat from wyoming and the evolution of flight and echolocation. Nature 451: 818-821.
Simmons NB, D Wilson, D Reeder.2005. Order chiroptera. Mammal species of the world:a taxonomic and geographic reference 1:312-529. Johns Hopkins University Press.
Speakman JR, A Rowland.1999. Preparing for inactivity:How insectivorous bats deposit a fat store for hibernation. P Nutr Soc 58:123-131.
Stawski C, C Turbill, F Geiser.2009. Hibernation by a free-ranging subtropical bat (Nyctophilus bifax). J Comp Physiol B 179:433-441.
Stier A, P Bize, C Habold, F Bouillaud, S Massemin, F Criscuolo.2013. Mitochondrial uncoupling prevents cold-induced oxidative stress:A case study using ucpl knock-out mice. J Exp Biol 217:624-630.
Storey KB.1997. Metabolic regulation in mammalian hibernation:Enzyme and protein adaptations. Comp Biochem Phys A118:1115-1124.
Storey KB.2010. Out cold:Biochemical regulation of mammalian hibernation-a mini-review. Gerontology 56:220-230.
Storey KB, JM Storey.1990. Metabolic rate depression and biochemical adaptation in anaerobiosis, hibernation and estivation. Q Rev Biol 65:145-174.
T(?)ien 0, K Drew, M Chao, M Rice.2001. Ascorbate dynamics and oxygen consumption during arousal from hibernation in arctic ground squirrels. Am J Physiol-Reg 1281:572-583.
Takekoshi K, M Motooka, K Isobe, F Nomura, T Manmoku, K Ishii et al.1999. Leptin directly stimulates catecholamine secretion and synthesis in cultured porcine adrenal medullary chromaffin cells. Biochem Bioph Res Co 261:426-431.
Tartaglia LA.1997. The leptin receptor. J Biol Chem 272:6093-6096.
Tartaglia LA, M Dembski, X Weng, N Deng, J Culpepper, R Devos et al.1995. Identification and expression cloning of a leptin receptor, OB-R. Cell 83:1263-1271.
Teeling EC, MS Springer, O Madsen, P Bates, SJ O'brien, WJ Murphy.2005. A molecular phylogeny for bats illuminates biogeography and the fossil record. Science 307:580-584.
Thomas DW, D Cloutier.1992. Evaporative water loss by hibernating little brown bats, myotis lucifugus. Physiol Zool 65:443-456.
Thomas DW, D CLOUTIER, D GAGNE.1990a. Arrhythmic breathing, apnea and non-steadystate oxygen uptake in hibernating little brown bats (Myotis lucifugus). J Exp Biol 149:395-406.
Thomas DW, M Dorais, J-M Bergeron.1990b. Winter energy budgets and cost of arousals for hibernating little brown bats (Myotis lucifugus). J Mammal 71: 475-479.
Townsend KL, TH Kunz, EP Widmaier.2008. Changes in body mass, serum leptin, and mrna levels of leptin receptor isoforms during the premigratory period in myotis lucifugus. J Comp Physiol B 178:217-223.
Trayhurn P, JH Beattie.2001. Physiological role of adipose tissue:White adipose tissue as an endocrine and secretory organ. P Nutr Soc 60:329-339.
Trayhurn P, IS Wood.2004. Adipokines:Inflammation and the pleiotropic role of white adipose tissue. Brit J Nutr 92:347-355.
Tseng Y-H, E Kokkotou, TJ Schulz, TL Huang, JN Winnay, CM Taniguchi et al.2008. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454:1000-1004.
Turbill C, F Geiser.2008. Hibernation by tree-roosting bats. J Comp Physiol B 178: 597-605.
Vaisse C, JL Halaas, CM Horvath, JE Darnell, Jr., M Stoffel, JM Friedman.1996. Leptin activation of stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet 14:95-97.
van Breukelen F, SL Martin.2002. Molecular biology of thermoregulation-invited review:Molecular adaptations in mammalian hibernators:Unique adaptations or generalized responses? J Appl Physiol 92:2640-2647.
Van Gaal LF, IL Mertens, E Christophe.2006. Mechanisms linking obesity with cardiovascular disease. Nature 444:875-880.
van Marken Lichtenbelt WD, JW Vanhommerig, NM Smulders, JM Drossaerts, GJ Kemerink, ND Bouvy et al.2009. Cold-activated brown adipose tissue in healthy men. New Engl J Med 360:1500-1508.
Walden TB, IR Hansen, JA Timmons, B Cannon, J Nedergaard.2012. Recruited vs. Nonrecruited molecular signatures of brown,"brite," and white adipose tissues. Am J Physiol-Endoc M 302:19-31.
Wang Y, MA Beydoun, L Liang, B Caballero, SK Kumanyika.2008. Will all americans become overweight or obese? Estimating the progression and cost of the us obesity epidemic. Obesity 16:2323-2330.
Wang Y, J Mi, X Shan, QJ Wang, K Ge.2007. Is china facing an obesity epidemic and the consequences? The trends in obesity and chronic disease in china. Int J Obesity 31:177-188.
Wianny F, M Zernicka-Goetz.2000. Specific interference with gene function by double-stranded rna in early mouse development. Nat Cell Biol 2:70-75.
Wilkinson GS, JM South.2002. Life history, ecology and longevity in bats. Aging cell 1:124-131.
Wilson DE.2005. Mammal species of the world:A taxonomic and geographic reference. Johns Hopkins University Press.
Wojciechowski MS, M Jefimow, E Tegowska.2007. Environmental conditions, rather than season, determine torpor use and temperature selection in large mouse-eared bats (Myotis myotis). Comp Biochem Phys A 147:828-840.
Wu J, P Bostrom, LM Sparks, L Ye, JH Choi, A-H Giang et al.2012. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366-376.
Xu L, C He, C Shen, T Jiang, L Shi, K Sun et al.2010. Phylogeography and population genetic structure of the great leaf-nosed bat (Hipposideros armiger) in china. J Hered 101:562-572.
Xue Y, N Petrovic, R Cao, O Larsson, S Lim, S Chen et al.2009. Hypoxia-independent angiogenesis in adipose tissues during cold acclimation. Cell Metab 9:99-109.
Ye L, J Wu, P Cohen, L Kazak, MJ Khandekar, MP Jedrychowski et al.2013. Fat cells directly sense temperature to activate thermogenesis. P Natl A Sci 110:12480-12485.
Yu W, M Kimura, A Walczewska, S Karanth, S McCann.1997. Role of leptin in hypothalamic-pituitary function. P Natl A Sci 94:1023-1028.
Yuan LH, XD Zhao, BF Lin, SJ Rossiter, LJ He, XG Zuo et al.2011. Adaptive evolution of leptin in heterothermic bats. PLoS One 6 e27189.
Zatzman ML.1984. Renal and cardiovascular effects of hibernation and hypothermia. Cryobiology 21:593-614.
Zhang F, MB Basinski, JM Beals, SL Briggs, LM Churgay, DK Clawson et al.1997. Crystal structure of the obese protein ieptin-E100. Nature 387:206-209.
Zhang Y, R Proenca, M Maffei, M Barone, L Leopold, JM Friedman.1994. Positional cloning of the mouse obese gene and its human homologue. Nature 372:425-432,
Ziylan YZ, AK Baltaci, R Mogulkoc.2009. Leptin transport in the central nervous system. Cell Biochem Funct 27:63-70.
顾卫琼,陈名道.1999.中国人血清瘦素水平与肥胖度的关系.中华内分泌代谢杂志15：15-18.
Ahima RS, SY Osei.2004. Leptin signaling. Physiol Behav 81:223-241.
Akasaka Y, M Tsunoda, T Ogata, T Ide, K Murakami.2010. Direct evidence for leptin-induced lipid oxidation independent of long-form leptin receptor. Biochim Biophys Acta 1801:1115-1122.
Alessi M, F Peiretti, P Morange, M Henry, G Nalbone, I Juhan-Vague.1997. Production of plasminogen activator inhibitor by human adipose tissue: Possible link between visceral fat accumulation and vascular disease. Diabetes 46:860-867.
Alexopoulos N, D Katritsis, P Raggi.2014. Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis. Atherosclerosis. In press.
Andrews MT.2004. Genes controlling the metabolic switch in hibernating mammals. Biochem Soc Trans 32:1021-1024.
Anufriev A, T Solomonova, G Arkhipov, A Turpanov, N Solomonov.2003. Bat (vespertilionidae) hibernation in the northeastemmost part of their geographic range. Dokl Bio Sci 392:413-415.
Ashrafi K, FY Chang, JL Watts, AG Fraser, RS Kamath, J Ahringer et al.2003. Genome-wide rnai analysis of caenorhabditis elegans fat regulatory genes. Nature 421:268-272.
Audet D, MB Fenton.1988. Heterothermy and the use of torpor by the bat eptesicus fuscus (chiroptera:Vespertilionidae):A field study. Physiol Zool 61:197-204.
Audet D, DW Thomas.1996. Evaluation of the accuracy of body temperature measurement using external radio transmitters. Can J Zoolog 74:1778-1781.
Bai Y, S Zhang, K-S Kim, J-K Lee, K-H Kim.1996. Obese gene expression alters the ability of 30A5 preadipocytes to respond to lipogenic hormones. J Biol Chem 271:13939-13942.
Banks WA, SA Farr, JE Morley.2006. The effects of high fat diets on the blood-brain barrier transport of leptin:Failure or adaptation? Physiol Behav 88:244-248.
Barbatelli G, I Murano, L Madsen, Q Hao, M Jimenez, K Kristiansen et al.2010. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol-Endoc M 298:1244-1253.
Barnes BM.1989. Freeze avoidance in a mammal:Body temperatures below 0℃ in an arctic hibernator. Science 244:1593-1595.
Bartelt A, J Heeren.2014. Adipose tissue browning and metabolic health. Nat Rev Endocrinol 10:24-36.
Bartholomew GA, TJ Cade.1957. Temperature regulation, hibernation, and aestivation in the little pocket mouse, perognathus longimembris. J Mammal 38:60-72.
Bostrom P, J Wu, MP Jedrychowski, A Korde, L Ye, JC Lo et al.2012. A pgc-1α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481:463-468.
Bouret SG, SH Bates, S Chen, MG Myers, Jr., RB Simerly.2012. Distinct roles for specific leptin receptor signals in the development of hypothalamic feeding circuits. J Neurosci 32:1244-1252.
Bowlin MS, M Wikelski.2008. Pointed wings, low wingloading and calm air reduce migratory flight costs in songbirds. PLoS One 3:e2154.
Brack Jr V, JW Twente.1985. The duration of the period of hibernation of three species of vespertilionid bats. I. Field studies. Can J Zoolog 63:2952-2954.
Bray G.2003. Obesity is a chronic, relapsing neurochemical disease. Int J Obesity 28: 34-38.
Bray GA.2006. Obesity:The disease. J Med Chem 49:4001-4007.
Bray GA, LA Tartaglia.2000. Medicinal strategies in the treatment of obesity. Nature 404:672-677.
Campfield LA, FJ Smith, Y Guisez, R Devos, P Burn.1995. Recombinant mouse ob protein:Evidence for a peripheral signal linking adiposity and central neural networks. Science 269:546-549.
Cannon B, J Nedergaard.2004. Brown adipose tissue:Function and physiological significance. Physiol Rev 84:277-359.
Cannon B, J Nedergaard.2012. Neither brown nor white. Nature 488:286-287.
Carey HV, MT Andrews, SL Martin.2003. Mammalian hibernation:Cellular and molecular responses to depressed metabolism and low temperature. Physiol Rev 83:1153-1181.
Catalanotto C, G Azzalin, G Macino, C Cogoni.2000. Gene silencing in worms and fungi. Nature 404:245-245.
Chehab FF, K Mounzih, R Lu, ME Lim.1997. Early onset of reproductive function in normal female mice treated with leptin. Science 275:88-90.
Chen H, O Charlat, LA Tartaglia, EA Woolf, X Weng, SJ Ellis et al.1996. Evidence that the diabetes gene encodes the leptin receptor:Identification of a mutation in the leptin receptor gene in db/db mice. Cell 84:491-495.
Chen Q, T Zhu, G Jones, J Zhang, Y Sun.2013. First knockdown gene expression in bat (Hipposideros armiger) brain mediated by lentivirus. Mol Biotechnol 54: 564-571.
Cheng H-C, L-L Lee.2004. Temporal variations in the size and composition of formosan leaf-nosed bat(Hipposideros terasensis) colonies in central taiwan. Zool Stud 43:787-794.
Cinti S.2001. The adipose organ:Morphological perspectives of adipose tissues. P Nutr Soc.60:319-328.
Concannon P, K Levac, R Rawson, B Tennant, A Bensadoun.2001. Seasonal changes in serum leptin, food intake, and body weight in photoentrained woodchucks. Am J Physiol Regul Integr Comp Physiol 281:951-959.
Considine RV, MK Sinha, ML Heiman, A Kriauciunas, TW Stephens, MR Nyce et al. 1996. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292-295.
Cotton C, H Harlow.1995. Fasting biochemistry of representative spontaneous and facultative hibernators:The white-tailed prairie dog and the black-tailed prairie dog. Physiol Zoolog 68:915-934.
Cypess AM, S Lehman, G Williams, I Tal, D Rodman, AB Goldfine et al.2009. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360:1509-1517.
Daan S.1972. Activity during natural hibernation in three species of vespertilionid bats. Neth J Zoo123:1-71.
Daan S, BM Barnes, AM Strijkstra.1991. Warming up for sleep? Ground squirrels sleep during arousals from hibernation. Neurosci Lett 128:265-268.
Dalamaga M, SH Chou, K Shields, P Papageorgiou, SA Polyzos, CS Mantzoros.2013. Leptin at the intersection of neuroendocrinology and metabolism:Current evidence and therapeutic perspectives. Cell Metab 18:29-42.
Dausmann KH.2005. Measuring body temperature in the field—evaluation of external vs. Implanted transmitters in a small mammal. J Therm Biol 30:195-202.
Davis DE, RH Swade.1983. Circannual rhythm of torpor and molt in the ground squirrel, Spermophilus beecheyi. Comp Bioche Phys A 76:183-187.
De Vos P, M Guerre-Millot, A Leturque, J Girard, B Staels, J Auwerx.1995. Transient increase in obese gene expression after food intake or insulin administration. Nature 377:527-528
Domanski MJ, KA Jablonski, MM Rice, SE Fowler, E Braunwald.2006. Obesity and cardiovascular events in patients with established coronary disease. Eur Heart J 27:1416-1422.
Drew KL, CL Buck, BM Barnes, SL Christian, BT Rasley, MB Harris.2007. Central nervous system regulation of mammalian hibernation:Implications for metabolic suppression and ischemia tolerance. J Neurochem 102:1713-1726.
Du T, X Sun, P Yin, R Huo, C Ni, X Yu.2013. Increasing trends in central obesity among Chinese adults with normal body mass index,1993-2009. BMC Public Health 13:327.
Dunbar MB, TE Tomasi.2006. Arousal patterns, metabolic rate, and an energy budget of eastern red bats (lasiurus borealis) in winter. J Mammal 87:1096-1102.
Ewing WG, EH Studier, MJ OTarrell.1970. Autumn fat deposition and gross body composition in three species of myotis. Comp Biochem Physiol 36:119-129.
Finkelstein EA, IC Fiebelkorn, G Wang.2003. National medical spending attributable to overweight and obesity:How much, and who's paying? Health Affair 22: 219-226.
Fleming TH, P Eby, T Kunz, M Fenton.2003. Ecology of bat migration. Bat ecology. 156-208.
Florant GL.1998. Lipid metabolism in hibernators:The importance of essential fatty acids. Am Zool 38:331-340.
Fruhbeck G, M Aguado, JA Martinez.1997. In vitro lipolytic effect of leptin on mouse adipocytes:Evidence for a possible autocrine/paracrine role of leptin. Biochem Bioph Res Co 240:590-594.
Freeman DA, DA Lewis, AS Kauffinan, RM Blum, J Dark.2004. Reduced leptin concentrations are permissive for display of torpor in Siberian hamsters. Am J of Physiol-Reg 1287:R97-R103.
French AR.1985. Allometries of the durations of torpid and euthermic intervals during mammalian hibernation:Atest of the theory of metabolic control of the timing of changes in body temperature. J Comp Physiol B 156:13-19.
Frerichs KU.1999. Neuroprotective strategies in nature—novel clues for the treatment of stroke and trauma. Acta Neurochir Suppl 73:57-61.
Frerichs KU, JM Hallenbeck.1998. Hibernation in ground squirrels induces state and species-specific tolerance to hypoxia and aglycemia:An in vitro study in hippocampal slices. J Cereb Blood Flow Metab 18:168-175.
Gainsford T, TA Willson, D Metcalf, E Handman, C McFarlane, A Ng et al.1996. Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. P Natl A Sci 93:14564-14568.
Geiser F.1988. Reduction of metabolism during hibernation and daily torpor in mammals and birds:Temperature effect or physiological inhibition? J Comp Physiol B 158:25-37.
Geiser F.2004. Metabolic rate and body temperature reduction during hibernation and daily torpor. Annu Rev Physiol 66:239-274.
Geiser F.2013. Hibernation. Curr Biol 23:R188-R193.
Geiser F, RM Brigham.2012. The other functions of torpor. Living in a seasonal world. 109-121.
Geiser F, C Turbill.2009. Hibernation and daily torpor minimize mammalian extinctions. Naturwissenschaften 96:1235-1240.
Golden PL, TJ Maccagnan, WM Pardridge.1997. Human blood-brain barrier leptin receptor. Binding and endocytosis in isolated human brain microvessels. J Clin Invest 99:14-18.
Grunfeld C, C Zhao, J Fuller, A Pollack, A Moser, J Friedman et al.1996. Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. J Clin Invest 97:2152-2157.
Gunnell GF, NB Simmons.2005. Fossil evidence and the origin of bats. J Mamm Evol 12:209-246.
Halaas JL, KS Gajiwala, M Maffei, SL Cohen, BT Chait, D Rabinowitz et al.1995. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543-546.
Halsall AL, JG Boyles, JO Whitaker.2012. Body temperature patterns of big brown bats during winter in a building hibernaculum. J Mammal 93:497-503.
Harms M, P Seale.2013. Brown and beige fat:Development, function and therapeutic potential. Nat Med 19:1252-1263.
Harris MB, WK Milsom.1995. Parasympathetic influence on heart rate in euthermic and hibernating ground squirrels. J Exp Biol 198:931-937.
He L, Y Pan, G He, B Lin, CC Liao, X Zuo et al.2010. Structural and functional studies of leptins from hibernating and non-hibernating bats. Gen Comp Endocrinol 168:29-35.
Heldmaier G, T Ruf.1992. Body temperature and metabolic rate during natural hypothermia in endotherms. J Comp Physiol B 162:696-706.
Henson MC, VD Castracane.2000. Leptin in pregnancy. Biol Reprod 63:1219-1228.
Hiebert SM, EM Thomas, TM Lee, KM Pelz, SM Yellon, I Zucker.2000. Photic entrainment of circannual rhythms in golden-mantled ground squirrels:Role of the pineal gland. J Biol Rhythm 15:126-134.
Hileman SM, J Torn(?)e, JS Flier, C Bjorbaek.2000. Transcellular transport of leptin by the short leptin receptor isoform obra in madin-darby canine kidney cells 1. Endocrinology 141:1955-1961.
Hill JE, JD Smith.1984. Bats:A natural history. Cambridge University Press.
Ho Y-Y, L-L Lee.2003. Roost selection by formosan leaf-nosed bats (Hipposideros armiger terasensis). Zool Sci 20:1017-1024.
Hock RJ.1951. The metabolic rates and body temperatures of bats. Biol Bull 101:289-299.
Hoffman RA, PF Robinson, H Magalhaes.1968. The golden hamster:Its biology and use in medical research. The Iowa State University Press.
Holland RA, DA Waters.2005. Echolocation signals and pinnae movement in the fruitbat rousettus aegyptiacus. Acta Chiropterol 7:83-90.
Holland RA, DA Waters, JM Rayner.2004. Echolocation signal structure in the megachiropteran bat rousettus aegyptiacus geoffroy 1810. J Exp Biol 207: 4361-4369.
Hope PR, G Jones.2012. Warming up for dinner:Torpor and arousal in hibernating natterer's bats (Myotis nattereri) studied by radio telemetry. J Comp Physiol B 182:569-578.
Hubert HB, M Feinleib, PM McNamara, WP Castelli.1983. Obesity as an independent risk factor for cardiovascular disease:A 26-year follow-up of participants in the framingham heart study. Circulation 67:968-977.
Jepsen GL.1966. Early eocene bat from wyoming. Science 154:1333-1339.
Jespersen NZ, TJ Larsen, L Peijs, S Daugaard, P Hom(?)e, A Loft et al.2013. A classical brown adipose tissue mrna signature partly overlaps with brite in the supraclavicular region of adult humans. Cell Metab 17:798-805.
Jia W, K Xiang, L Chen, J Lu, Y Wu.2002. Epidemiological study on obesity and its comorbidities in urban Chinese older than 20 years of age in shanghai, china. ObesRev 3:157-165.
Johnson JS, MJ Lacki, SC Thomas, JF Grider.2012. Frequent arousals from winter torpor in rafinesque's big-eared bat (Corynorhinus rafinesquii). PLoS One 7: e49754.
Jonasson KA, CK Willis.2011. Changes in body condition of hibernating bats support the thrifty female hypothesis and predict consequences for populations with white-nose syndrome. P1oS one 6:e21061.
Jones KE, A Purvis, A Maclarnon, OR BININDA-EMONDS, NB Simmons.2002. A phylogenetic supertree of the bats (mammalia:Chiroptera). Biol Rev 77: 223-259.
Kortner G, F Geiser.2000. Torpor and activity patterns in free-ranging sugar gliders petaurus breviceps (marsupialia). Oecologia 123:350-357.
Kafri T, U Blomer, DA Peterson, FH Gage, IM Verma.1997. Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors. Nat Genet 17:314-317.
Kallen F.1977. The cardiovascular system of bats:Structure and function. Biol Bat 3: 289-483.
Katsuura G, A Asakawa, A Inui.2002. Roles of pancreatic polypeptide in regulation of food intake. Peptides 23:323-329.
Konturek P, J Konturek, M Czesnikiewicz-Guzik, T Brzozowski, E Sito, S Konturek. 2005. Neuro-hormonal control of food intake:Basic mechanisms and clinical implications. J Physiol Pharmacol 56:5-25.
Kowalski TJ, S-M Liu, RL Leibel, SC Chua.2001. Transgenic complementation of leptin-receptor deficiency i. Rescue of the obesity/diabetes phenotype of lepr-null mice expressing a lepr-b transgene. Diabetes 50:425-435.
Kronfeld-Schor N, C Richardson, BA Silvia, TH Kunz, EP Widmaier.2000. Dissociation of leptin secretion and adiposity during prehibernatory fattening in little brown bats. Am J Physiol Regul Integr Comp Physiol 279:1277-1281.
Kulzer E.1967. Die herztatigkeit bei lethargischen und winterschlafenden fledermausen. Z Vergl Physiol 56:63-94.
Kunz TH, MB Fenton.2006. Bat ecology. University of Chicago Press.
Kunz TH, JA Wrazen, C Burnett.1998. Changes in body mass and fat reserves in pre-hibernating little brown bats (Myotis lucifugus). Ecoscience 5:8-17.
Ladyman SR, DR Grattan.2005. Suppression of leptin receptor messenger ribonucleic acid and leptin responsiveness in the ventromedial nucleus of the hypothalamus during pregnancy in the rat. Endocrinology 146:3868-3874.
Lee K, JY Park, W Yoo, T Gwag, JW Lee, MW Byun et al.2008. Overcoming muscle atrophy in a hibernating mammal despite prolonged disuse in dormancy: Proteomic and molecular assessment. J Cell Biochem 104:642-656.
Lee M, I Choi, K Park.2002. Activation of stress signaling molecules in bat brain during arousal from hibernation. J Neurochem 82:867-873.
Lementowski PW, SB Zelicof.2008. Obesity and osteoarthritis. Am J Orthop 37:148-151.
Li W, Z Shi, M Yu, W Ren, C Smith, JH Epstein et al.2005. Bats are natural reservoirs of sars-like coronaviruses. Science 310:676-679.
Lidell ME, MJ Betz, OD Leinhard, M Heglind, L Elander, M Slawik et al.2013. Evidence for two types of brown adipose tissue in humans. Nat Med 19:631-634.
Lim S, J Honek, Y Xue, T Seki, Z Cao, P Andersson et al.2012. Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice. Nat Protoc 7:606-615.
Liu JN, WH Karasov.2011 Hibernation in warm hibernacula by free-ranging formosan leaf-nosed bats (Hipposideros terasensis) in subtropical taiwan. J Comp Physio1B181:125-135.
Livak KJ, TD Schmittgen.2001. Analysis of relative gene expression data using real-time quantitative per and the 2-△△ct method. Methods 25:402-408.
Lyman C, P Chatfield.1955. Physiology of hibernation in mammals. Physiol Rev 35: 403-425.
Lyman C, J Willis, A Malan, L Wang.1982. Hibernation and torpor in mammals and birds. New York Academic Press.
Margetic S, C Gazzola, G Pegg, R Hill.2002. Leptin:A review of its peripheral actions and interactions. Int J Obesity 26:1407-1433.
McGee-Lawrence ME, HV Carey, SW Donahue.2008. Mammalian hibernation as a model of disuse osteoporosis:The effects of physical inactivity on bone metabolism, structure, and strength. Am J Physiol-Reg I 295:1999-2014.
Menaker M.1964. Frequency of spontaneous arousal from hibernation in bats. Nature 203:540-541.
Mercer JG, N Hoggard, LM Williams, CB Lawrence, LT Hannah, P Trayhurn.1996. Localization of leptin receptor mrna and the long form splice variant (ob-rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Lett 387:113-116.
Messier SP.2009. Obesity and osteoarthritis:Disease genesis and nonpharmacologic weight management. Med Clin N Am 93:145-159.
Muoio DM, GL Dohn, FT Fiedorek, EB Tapscott, RA Coleman.1997. Leptin directly alters lipid partitioning in skeletal muscle. Diabetes 46:1360-1363.
Nedergaard J, B Cannon.2013. Ucpl mRNA does not produce heat. BBA-Mol Cell BiolL 1831:943-949.
Ollivier F, D Samuelson, D Brooks, P Lewis, M Kallberg, A Komaromy.2004. Comparative morphology of the tapetum lucidum (among selected species). Vet Ophthalmol 7:11-22.
Organization WH.1997. Preventing and managing the global epidemic-report of a who consultation on obesity. Geneva, World Health Organization.
Organization WH.2000. Obesity:Preventing and managing the global epidemic. Geneva, World Health Organization.
Organization WH.2010. Obesity and overweight:Fact sheet no.311. Geneva, World Health Organization.
Ormseth OA, M Nicolson, MA Pelleymounter, BB Boyer.1996. Leptin inhibits prehibernation hyperphagia and reduces body weight in arctic ground squirrels. Am J Physiol 271:1775-1779.
Otero M, Ro Lago, F Lago, FF Casanueva, C Dieguez, JJ Gomez-Reino et al.2005. Leptin, from fat to inflammation:Old questions and new insights. FEBS letters 579:295-301.
Pakhotin PI, ID Pakhotina, AB Belousov.1993. The study of brain slices from hibernating mammals in vitro and some approaches to the analysis of hibernation problems in vivo. Prog Neurobiol 40:123-161.
Pan Y-H, Y Zhang, J Cui, Y Liu, BM McAllan, C-C Liao et al.2013. Adaptation of phenylalanine and tyrosine catabolic pathway to hibernation in bats. P1oS one 8:e62039.
Park KJ, G Jones, RD Ransome.2000. Torpor, arousal and activity of hibernating greater horseshoe bats (Rhinolophusferrumequinum). Funct Ecol 14:580-588.
Patterson BD, MR Willig, RD Stevens.2003. Trophic strategies, niche partitioning, and patterns of ecological organization. Bat Ecol 9:536-557.
Paxinos G.2004. The mouse brain in stereotaxic coordinates. Gulf Professional Publishing.
Pelleymounter MA, MJ Cullen, MB Baker, R Hecht, D Winters, T Boone et al.1995. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540-543.
Pengelley E, SJ Asmundson, B Barnes, RC Aloia.1976. Relationship of light intensity and photoperiod to circannual rhythmicity in the hibernating ground squirrel, citellus lateralis. Comp Biochem Phys A 53:273-277.
Pereira MJR, H Rebelo, EC Teeling, SJ O'Brien, I Mackie, SSH Bu et al.2006. Status of the world's smallest mammal, the bumble-bee bat (craseonycteris thonglongyai) in myanmar. Oryx 40:456-463.
Petrovic N, TB Walden, IG Shabalina, JA Timmons, B Cannon, J Nedergaard.2010. Chronic peroxisome proliferator-activated receptor y (ppary) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, ucpl-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem 285:7153-7164.
Prendergast BJ, DA Freeman, I Zucker, RJ Nelson.2002. Periodic arousal from hibernation is necessary for initiation of immune responses in ground squirrels. Am J Physiol-Reg I 282:1054-1062.
Qian H, GJ Hausman, MM Compton, MJ Azain, DL Hartzell, CA Baile.1998. Leptin regulation of peroxisome proliferator-activated receptor-y, tumor necrosis factor, and uncoupling protein-2 expression in adipose tissues. Biochem Bioph Res Co 246:660-667.
Reidy SP, J-M Weber.2000. Leptin:An essential regulator of lipid metabolism. Comp Biochem Phys A 125:285-298.
Reite OB, WH Davis.1966. Thermoregulation in bats exposed to low ambient temperatureis. Exper Biol Med 121:1212-1215.
Resnick HE, P Valsania, JB Halter, X Lin.2000. Relation of weight gain and weight loss on subsequent diabetes risk in overweight adults. J Epidemiol Commun H 54:596-602.
Roignant JY, C Carre, B Mugat, D Szymczak, JA Lepesant, C Antoniewski.2003. Absence of transitive and systemic pathways allows cell-specific and isoform-specific rnai in drosophila. Rna 9:299-308.
Rosell M, M Kaforou, A Frontini, A Okolo, Y-W Chan, E Nikolopoulou et al.2014. Brown and white adipose tissues. Intrinsic differences in gene expression and response to cold exposure in mice. Am J Physiol-Endoc M. In Press.
Rosen ED, BM Spiegelman.2006. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 444:847-853.
Rousseau K, Z Atcha, A Loudon.2003. Leptin and seasonal mammals. J Neuroendocrinol 15:409-414.
Saad MF, A Khan, A Sharma, R Michael, MG Riad-Gabriel, R Boyadjian et al.1998. Physiological insulinemia acutely modulates plasma leptin. Diabetes 47:544-549.
Sarmiento U, B Benson, S Kaufman, L Ross, M Qi, S Scully et al.1997. Morphologic and molecular changes induced by recombinant human leptin in the white and brown adipose tissues of C57 BL/6 mice. Lab Invest 77:243-256.
Sarraf P, RC Frederich, EM Turner, G Ma, NT Jaskowiak, DJ Rivet et al.1997. Multiple cytokines and acute inflammation raise mouse leptin levels:Potential role in inflammatory anorexia. J Exp Med 185:171-176.
Schaffler A, J Scholmerich, C Buchler.2005. Mechanisms of disease:Adipocytokines and visceral adipose tissue-emerging role in nonalcoholic fatty liver disease. Nat Clin Pract Gastr 2:273-280.
Schaffhauser A, A Stricker-Krongrad, L Brunner, F Cumin, C Gerald, S Whitebread et al.1997. Inhibition of food intake by neuropeptide Y Y5 receptor antisense oligodeoxynucleotides. Diabetes 46:1792-1798.
Schulz TJ, TL Huang, TT Tran, H Zhang, KL Townsend, JL Shadrach et al.2011. Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat. P Natl A Sci 108:143-148.
Schwartz MW, SC Woods, D Porte, RJ Seeley, DG Baskin.2000. Central nervous system control of food intake. Nature 404:661-671.
Seale P, B Bjork, W Yang, S Kajimura, S Chin, S Kuang et al.2008. Prdml6 controls a brown fat/skeletal muscle switch. Nature 454:961-967.
Shigemura N, H Miura, Y Kusakabe, A Hino, Y Ninomiya.2003. Expression of leptin receptor (ob-r) isoforms and signal transducers and activators of transcription (stats) mrnas in the mouse taste buds. Arch Histol Cytol 66:253-260.
Shore AM, A Karamitri, P Kemp, JR Speakman, NS Graham, MA Lomax.2013. Cold-induced changes in gene expression in brown adipose tissue, white adipose tissue and liver. P1oS one 8:e68933.
Siegrist-Kaiser CA, V Pauli, CE Juge-Aubry, O Boss, A Pernin, WW Chin et al.1997. Direct effects of leptin on brown and white adipose tissue. J Clin Invest 100: 2858-2864.
Sierra-Honigmann MR, AK Nath, C Murakami, G Garcia-Cardena, A Papapetropoulos, WC Sessa et al.1998. Biological action of leptin as an angiogenic factor. Science 281:1683-1686.
Simmons NB, JH Geisler.1998. Phylogenetic relationships of icaronycteris, archaeonycteris, hassianycteris, and palaeochiropteryx to extant bat lineages, with comments on the evolution of echolocation and foraging strategies in microchiroptera. B Am Mus Nat Hist no.235.
Simmons NB, KL Seymour, J Habersetzer, GF Gunnell.2008. Primitive early eocene bat from wyoming and the evolution of flight and echolocation. Nature 451: 818-821.
Simmons NB, D Wilson, D Reeder.2005. Order chiroptera. Mammal species of the world:a taxonomic and geographic reference 1:312-529. Johns Hopkins University Press.
Speakman JR, A Rowland.1999. Preparing for inactivity:How insectivorous bats deposit a fat store for hibernation. P Nutr Soc 58:123-131.
Stawski C, C Turbill, F Geiser.2009. Hibernation by a free-ranging subtropical bat (Nyctophilus bifax). J Comp Physiol B 179:433-441.
Stier A, P Bize, C Habold, F Bouillaud, S Massemin, F Criscuolo.2013. Mitochondrial uncoupling prevents cold-induced oxidative stress:A case study using ucpl knock-out mice. J Exp Biol 217:624-630.
Storey KB.1997. Metabolic regulation in mammalian hibernation:Enzyme and protein adaptations. Comp Biochem Phys A118:1115-1124.
Storey KB.2010. Out cold:Biochemical regulation of mammalian hibernation-a mini-review. Gerontology 56:220-230.
Storey KB, JM Storey.1990. Metabolic rate depression and biochemical adaptation in anaerobiosis, hibernation and estivation. Q Rev Biol 65:145-174.
T(?)ien 0, K Drew, M Chao, M Rice.2001. Ascorbate dynamics and oxygen consumption during arousal from hibernation in arctic ground squirrels. Am J Physiol-Reg 1281:572-583.
Takekoshi K, M Motooka, K Isobe, F Nomura, T Manmoku, K Ishii et al.1999. Leptin directly stimulates catecholamine secretion and synthesis in cultured porcine adrenal medullary chromaffin cells. Biochem Bioph Res Co 261:426-431.
Tartaglia LA.1997. The leptin receptor. J Biol Chem 272:6093-6096.
Tartaglia LA, M Dembski, X Weng, N Deng, J Culpepper, R Devos et al.1995. Identification and expression cloning of a leptin receptor, OB-R. Cell 83:1263-1271.
Teeling EC, MS Springer, O Madsen, P Bates, SJ O'brien, WJ Murphy.2005. A molecular phylogeny for bats illuminates biogeography and the fossil record. Science 307:580-584.
Thomas DW, D Cloutier.1992. Evaporative water loss by hibernating little brown bats, myotis lucifugus. Physiol Zool 65:443-456.
Thomas DW, D CLOUTIER, D GAGNE.1990a. Arrhythmic breathing, apnea and non-steadystate oxygen uptake in hibernating little brown bats (Myotis lucifugus). J Exp Biol 149:395-406.
Thomas DW, M Dorais, J-M Bergeron.1990b. Winter energy budgets and cost of arousals for hibernating little brown bats (Myotis lucifugus). J Mammal 71: 475-479.
Townsend KL, TH Kunz, EP Widmaier.2008. Changes in body mass, serum leptin, and mrna levels of leptin receptor isoforms during the premigratory period in myotis lucifugus. J Comp Physiol B 178:217-223.
Trayhurn P, JH Beattie.2001. Physiological role of adipose tissue:White adipose tissue as an endocrine and secretory organ. P Nutr Soc 60:329-339.
Trayhurn P, IS Wood.2004. Adipokines:Inflammation and the pleiotropic role of white adipose tissue. Brit J Nutr 92:347-355.
Tseng Y-H, E Kokkotou, TJ Schulz, TL Huang, JN Winnay, CM Taniguchi et al.2008. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454:1000-1004.
Turbill C, F Geiser.2008. Hibernation by tree-roosting bats. J Comp Physiol B 178: 597-605.
Vaisse C, JL Halaas, CM Horvath, JE Darnell, Jr., M Stoffel, JM Friedman.1996. Leptin activation of stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet 14:95-97.
van Breukelen F, SL Martin.2002. Molecular biology of thermoregulation-invited review:Molecular adaptations in mammalian hibernators:Unique adaptations or generalized responses? J Appl Physiol 92:2640-2647.
Van Gaal LF, IL Mertens, E Christophe.2006. Mechanisms linking obesity with cardiovascular disease. Nature 444:875-880.
van Marken Lichtenbelt WD, JW Vanhommerig, NM Smulders, JM Drossaerts, GJ Kemerink, ND Bouvy et al.2009. Cold-activated brown adipose tissue in healthy men. New Engl J Med 360:1500-1508.
Walden TB, IR Hansen, JA Timmons, B Cannon, J Nedergaard.2012. Recruited vs. Nonrecruited molecular signatures of brown,"brite," and white adipose tissues. Am J Physiol-Endoc M 302:19-31.
Wang Y, MA Beydoun, L Liang, B Caballero, SK Kumanyika.2008. Will all americans become overweight or obese? Estimating the progression and cost of the us obesity epidemic. Obesity 16:2323-2330.
Wang Y, J Mi, X Shan, QJ Wang, K Ge.2007. Is china facing an obesity epidemic and the consequences? The trends in obesity and chronic disease in china. Int J Obesity 31:177-188.
Wianny F, M Zernicka-Goetz.2000. Specific interference with gene function by double-stranded rna in early mouse development. Nat Cell Biol 2:70-75.
Wilkinson GS, JM South.2002. Life history, ecology and longevity in bats. Aging cell 1:124-131.
Wilson DE.2005. Mammal species of the world:A taxonomic and geographic reference. Johns Hopkins University Press.
Wojciechowski MS, M Jefimow, E Tegowska.2007. Environmental conditions, rather than season, determine torpor use and temperature selection in large mouse-eared bats (Myotis myotis). Comp Biochem Phys A 147:828-840.
Wu J, P Bostrom, LM Sparks, L Ye, JH Choi, A-H Giang et al.2012. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366-376.
Xu L, C He, C Shen, T Jiang, L Shi, K Sun et al.2010. Phylogeography and population genetic structure of the great leaf-nosed bat (Hipposideros armiger) in china. J Hered 101:562-572.
Xue Y, N Petrovic, R Cao, O Larsson, S Lim, S Chen et al.2009. Hypoxia-independent angiogenesis in adipose tissues during cold acclimation. Cell Metab 9:99-109.
Ye L, J Wu, P Cohen, L Kazak, MJ Khandekar, MP Jedrychowski et al.2013. Fat cells directly sense temperature to activate thermogenesis. P Natl A Sci 110:12480-12485.
Yu W, M Kimura, A Walczewska, S Karanth, S McCann.1997. Role of leptin in hypothalamic-pituitary function. P Natl A Sci 94:1023-1028.
Yuan LH, XD Zhao, BF Lin, SJ Rossiter, LJ He, XG Zuo et al.2011. Adaptive evolution of leptin in heterothermic bats. PLoS One 6 e27189.
Zatzman ML.1984. Renal and cardiovascular effects of hibernation and hypothermia. Cryobiology 21:593-614.
Zhang F, MB Basinski, JM Beals, SL Briggs, LM Churgay, DK Clawson et al.1997. Crystal structure of the obese protein ieptin-E100. Nature 387:206-209.
Zhang Y, R Proenca, M Maffei, M Barone, L Leopold, JM Friedman.1994. Positional cloning of the mouse obese gene and its human homologue. Nature 372:425-432,
Ziylan YZ, AK Baltaci, R Mogulkoc.2009. Leptin transport in the central nervous system. Cell Biochem Funct 27:63-70.
顾卫琼,陈名道.1999.中国人血清瘦素水平与肥胖度的关系.中华内分泌代谢杂志15：15-18.