鸡FTO基因：组织特异性表达、中枢核团定位、品种差异以及禁食的影响
摘要
FTO基因(fat mass and obesity-associated gene)是人类发现的第一个与非病理性肥胖相关的基因。人们对哺乳动物FTO基因的研究已经取得了一定的进展,但鸡FTO的研究目前仍属空白。本试验分析了鸡FTO基因的组织特异性表达以及日龄和品种的影响,并检测了FTO mRNA在鸡下丘脑和丘脑的分布以及下丘脑室旁核和腹内侧核FTO mRNA丰度表达的品种差异和进食的影响,为鸡FTO功能的进一步研究提供基础资料。
1鸡FTO基因的组织特异性表达以及日龄和品种的影响
本研究选择1周龄及19周龄的雄性罗斯(Ross)肉鸡和莱航(Leghorn)蛋鸡,采集下丘脑、端脑、小脑、肌肉、肝脏、内脏脂肪六种主要组织器官并采用实时定量荧光PCR方法检测FTO mRNA在不同组织器官中的表达。结果显示：FTO在所检测的六个组织器官中均有不同程度表达。其中,FTO在鸡的肝脏、下丘脑、内脏脂肪和小脑有较高丰度的表达,而肌肉和端脑表达丰度相对低。总的来说,周龄及品种对FTOmRNA的组织分布模式影响不大,但有些组织存在显著的周龄和品种差异。1周龄肉鸡肝脏中FTO的mRNA表达量极显著高于同周龄蛋鸡(P<0.01)；而内脏脂肪和小脑的FTO mRNA表达量则显著地低于蛋鸡(P<0.05)。19周龄蛋鸡肝脏和内脏脂肪中FTO的表达量均极显著高于1周龄蛋鸡(P<0.01)；19周龄肉鸡下丘脑FTO的mRNA表达水平显著高于1周龄肉鸡(P<0.05),小脑中FTO的mRNA表达量则极显著高于1周龄肉鸡(P<0.01)。
2 FTO在鸡-下丘脑及丘脑的表达分布
本研究采用原位杂交的方法检测FTO在鸡下丘脑和丘脑的表达分布情况。原位杂交结果显示：FTO基因在下丘脑调节能量平衡的室旁核(PVN, paraventricular nucleus)、腹内侧核(VMN, ventromedial nucleus)中有表达。FTO在丘脑与视觉、采食和生殖节律有关的豆状袢前核(ALA, ansae lenticularis anterior)、丘脑前背外侧核(DLA, nucleus dorsolateralis anterior)、枕中脑束(OM, Tractus occipitomesenphalicus)、外细胞层(SCE, stratum cellulare externum)、达克谢维奇(氏)核(ND, nucleus of Darkschewitsch)、中间核(nI, nucleus intramedialis)均有表达。
3禁食及品种差异对FTO在室旁核和腹内侧核表达的影响
选择1日龄雄性罗斯(Ross)肉鸡和莱航(Leghorn)蛋鸡,分别分为对照和24小时禁食组。限饲处理从第6日龄开始,7日龄时屠宰采集整脑,打孔(punch)收集下丘脑室旁核和腹内侧核,提取总RNA采用实时定量荧光PCR方法检测FTO mRNA在这些核团中的相对表达量。结果显示：肉鸡室旁核内FTO表达显著高于蛋鸡(P<0.05),而腹内侧核内FTO表达未表现品种差异。肉鸡下丘脑室旁核和腹内侧核中FTO基因表达均不受禁食的影响；而蛋鸡24小时禁食后,腹内侧核FTO基因表达量显著下降(P<0.05),室旁核FTO基因表达量没有显著变化。
FTO gene (fat mass and obesity-associated gene) is the first gene we have found contributing to common forms of human obesity. Studies in mammalian have made certain progress, but chicken FTO study is still vacant. In present study, we tested FTO gene tissue-specific expresssion, especially chickens with different ages and strains. FTO mRNA distribution pattern in chicken hypothalamus and thalamus was examined, as well the PVN and VMN FTO expression comparison between different food intake status and breeds.
1 FTO gene tissue specific expression in different ages and breeds of chicken
Hypothalamus, forebrain, cerebellum, muscle, liver and visceral fat were sampled from 1 week and 19 weeks old male Ross and Leghorn chicken. FTO gene expression in these tissue samples was tested with Real-time PCR. Our results showed that FTO gene was highly expressed in liver, hypothalamus, visceral fat and cerebellum. Although factors of age and strain did not affect the FTO expression pattern in different tissues very much, there are still some breed-specific and age-specific expressions in certain tissues.In breeds comparison, the FTO gene expression in 1 week old broiler liver is severely higher than 1 week layers (P<0.01); FTO expression in 1 week broiler visceral fat and cerebellum is significantly lower compared with 1 week layers (P<0.05). In ages comparison, FTO expression level in 19 weeks old layer liver and visceral fat were markedly higher than 1 week layers (P<0.01); FTO expression level in 19 weeks old broilers hypothalamus was higher than lweek layers(P<0.05), and in cerebellum was profoundly higher than 1 week layers (P<0.01).
2 FTO mRNA distributions in hypothalamus and thalamus
In this study we examined the FTO mRNA distribution pattern in hypothalamus and thalamus with in situ hybridization (ISH). Our ISH result shows that FTO gene expressed in hypothalamic PVN (paraventricular nucleus) and VMN (ventromedial nucleus), and in thylamic DLA (nucleus dorsolateralis anterior), ALA (ansae lenticularis anterior), OM (Tractus occipitomesenphalicus), SCE (stratum cellulare externum), D (nucleus of Darkschewitsch), nl (nucleus intramedialis). These nucleuses relate to food intake, visual and reproductive rhythm function.
3 Effects of fasting and breed on PVN and VMN FTO expression
1 week old male Ross and Leghorn chicken were divided into broiler 24 hours fasting group, broiler control, layer 24 hours fasting group and layer control. Nucleus of PVN and VMN were collected from hypothalamus by punch, and FTO mRNA levels were determined by Real-time PCR. Our result shows FTO breed specific expression in chicken PVN, that FTO expression in 1 week old broiler PVN is significantly higher than 1 week layers (P<0.05); no breed specific expression was detected in chicken VMN.24 hours fasting didn't affect both hypothalamic PVN and VMN FTO expression in 1 week male broilers. After the feed restriction, FTO expression level in VMN was significantly reduced (P<0.05), while no difference was found in PVN.
1鸡FTO基因的组织特异性表达以及日龄和品种的影响
本研究选择1周龄及19周龄的雄性罗斯(Ross)肉鸡和莱航(Leghorn)蛋鸡,采集下丘脑、端脑、小脑、肌肉、肝脏、内脏脂肪六种主要组织器官并采用实时定量荧光PCR方法检测FTO mRNA在不同组织器官中的表达。结果显示：FTO在所检测的六个组织器官中均有不同程度表达。其中,FTO在鸡的肝脏、下丘脑、内脏脂肪和小脑有较高丰度的表达,而肌肉和端脑表达丰度相对低。总的来说,周龄及品种对FTOmRNA的组织分布模式影响不大,但有些组织存在显著的周龄和品种差异。1周龄肉鸡肝脏中FTO的mRNA表达量极显著高于同周龄蛋鸡(P<0.01)；而内脏脂肪和小脑的FTO mRNA表达量则显著地低于蛋鸡(P<0.05)。19周龄蛋鸡肝脏和内脏脂肪中FTO的表达量均极显著高于1周龄蛋鸡(P<0.01)；19周龄肉鸡下丘脑FTO的mRNA表达水平显著高于1周龄肉鸡(P<0.05),小脑中FTO的mRNA表达量则极显著高于1周龄肉鸡(P<0.01)。
2 FTO在鸡-下丘脑及丘脑的表达分布
本研究采用原位杂交的方法检测FTO在鸡下丘脑和丘脑的表达分布情况。原位杂交结果显示：FTO基因在下丘脑调节能量平衡的室旁核(PVN, paraventricular nucleus)、腹内侧核(VMN, ventromedial nucleus)中有表达。FTO在丘脑与视觉、采食和生殖节律有关的豆状袢前核(ALA, ansae lenticularis anterior)、丘脑前背外侧核(DLA, nucleus dorsolateralis anterior)、枕中脑束(OM, Tractus occipitomesenphalicus)、外细胞层(SCE, stratum cellulare externum)、达克谢维奇(氏)核(ND, nucleus of Darkschewitsch)、中间核(nI, nucleus intramedialis)均有表达。
3禁食及品种差异对FTO在室旁核和腹内侧核表达的影响
选择1日龄雄性罗斯(Ross)肉鸡和莱航(Leghorn)蛋鸡,分别分为对照和24小时禁食组。限饲处理从第6日龄开始,7日龄时屠宰采集整脑,打孔(punch)收集下丘脑室旁核和腹内侧核,提取总RNA采用实时定量荧光PCR方法检测FTO mRNA在这些核团中的相对表达量。结果显示：肉鸡室旁核内FTO表达显著高于蛋鸡(P<0.05),而腹内侧核内FTO表达未表现品种差异。肉鸡下丘脑室旁核和腹内侧核中FTO基因表达均不受禁食的影响；而蛋鸡24小时禁食后,腹内侧核FTO基因表达量显著下降(P<0.05),室旁核FTO基因表达量没有显著变化。
FTO gene (fat mass and obesity-associated gene) is the first gene we have found contributing to common forms of human obesity. Studies in mammalian have made certain progress, but chicken FTO study is still vacant. In present study, we tested FTO gene tissue-specific expresssion, especially chickens with different ages and strains. FTO mRNA distribution pattern in chicken hypothalamus and thalamus was examined, as well the PVN and VMN FTO expression comparison between different food intake status and breeds.
1 FTO gene tissue specific expression in different ages and breeds of chicken
Hypothalamus, forebrain, cerebellum, muscle, liver and visceral fat were sampled from 1 week and 19 weeks old male Ross and Leghorn chicken. FTO gene expression in these tissue samples was tested with Real-time PCR. Our results showed that FTO gene was highly expressed in liver, hypothalamus, visceral fat and cerebellum. Although factors of age and strain did not affect the FTO expression pattern in different tissues very much, there are still some breed-specific and age-specific expressions in certain tissues.In breeds comparison, the FTO gene expression in 1 week old broiler liver is severely higher than 1 week layers (P<0.01); FTO expression in 1 week broiler visceral fat and cerebellum is significantly lower compared with 1 week layers (P<0.05). In ages comparison, FTO expression level in 19 weeks old layer liver and visceral fat were markedly higher than 1 week layers (P<0.01); FTO expression level in 19 weeks old broilers hypothalamus was higher than lweek layers(P<0.05), and in cerebellum was profoundly higher than 1 week layers (P<0.01).
2 FTO mRNA distributions in hypothalamus and thalamus
In this study we examined the FTO mRNA distribution pattern in hypothalamus and thalamus with in situ hybridization (ISH). Our ISH result shows that FTO gene expressed in hypothalamic PVN (paraventricular nucleus) and VMN (ventromedial nucleus), and in thylamic DLA (nucleus dorsolateralis anterior), ALA (ansae lenticularis anterior), OM (Tractus occipitomesenphalicus), SCE (stratum cellulare externum), D (nucleus of Darkschewitsch), nl (nucleus intramedialis). These nucleuses relate to food intake, visual and reproductive rhythm function.
3 Effects of fasting and breed on PVN and VMN FTO expression
1 week old male Ross and Leghorn chicken were divided into broiler 24 hours fasting group, broiler control, layer 24 hours fasting group and layer control. Nucleus of PVN and VMN were collected from hypothalamus by punch, and FTO mRNA levels were determined by Real-time PCR. Our result shows FTO breed specific expression in chicken PVN, that FTO expression in 1 week old broiler PVN is significantly higher than 1 week layers (P<0.05); no breed specific expression was detected in chicken VMN.24 hours fasting didn't affect both hypothalamic PVN and VMN FTO expression in 1 week male broilers. After the feed restriction, FTO expression level in VMN was significantly reduced (P<0.05), while no difference was found in PVN.
引文
[1]Loos RJ, Bouchard C. FTO:the first gene contributing to common forms of human obesity. Obes Rev 2008; 9:246-50.
[2]van der Hoeven F, Schimmang T, Volkmann A, Mattei MG, Kyewski B, Ruther U. Programmed cell death is affected in the novel mouse mutant Fused toes (Ft). Development 1994; 120:2601-7.
[3]Heymer J, Kuehn M, Ruther U. The expression pattern of nodal and lefty in the mouse mutant Ft suggests a function in the establishment of handedness. Mech Dev 1997; 66:5-11.
[4]Peters T, Ausmeier K, Dildrop R, Ruther U. The mouse Fused toes (Ft) mutation is the result of a 1.6-Mb deletion including the entire Iroquois B gene cluster. Mamm Genome 2002; 13:186-8.
[5]Peters T, Ausmeier K, Ruther U. Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation. Mamm Genome 1999; 10:983-6.
[6]Robbens S, Rouze P, Cock JM, Spring J, Worden AZ, Van de Peer Y. The FTO gene, implicated in human obesity, is found only in vertebrates and marine algae. J Mol Evol 2008; 66:80-4.
[7]Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316:889-94.
[8]Fredriksson R, Hagglund M, Olszewski PK, et al. The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 2008; 149:2062-71.
[9]Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318:1469-72.
[10]Dina C, Meyre D, Gallina S, et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 2007; 39:724-6.
[11]Scuteri A, Sanna S, Chen WM, et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007; 3:e115.
[12]Qi L, Kang K, Zhang C, et al. Fat mass-and obesity-associated (FTO) gene variant is associated with obesity:longitudinal analyses in two cohort studies and functional test. Diabetes 2008; 57: 3145-51.
[13]Stratigopoulos G, Padilla SL, LeDuc CA, et al. Regulation of Fto/Ftm gene expression in mice and humans. Am J Physiol Regul Integr Comp Physiol 2008; 294:R1185-96.
[14]Willer CJ, Speliotes EK, Loos RJ, et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009; 41:25-34.
[15]Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U. Inactivation of the Fto gene protects from obesity. Nature 2009.
[16]Horowitz SS, Blanchard JH, Morin LP. Intergeniculate leaflet and ventral lateral geniculate nucleus afferent connections:An anatomical substrate for functional input from the vestibulo-visuomotor system. J Comp Neurol 2004; 474:227-45.
[17]Hinney A, Nguyen TT, Scherag A, et al. Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS ONE 2007;2:e1361.
[18]Andreasen CH, Stender-Petersen KL, Mogensen MS, et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 2008; 57:95-101.
[19]Reinehr T, Hinney A, Toschke AM, Hebebrand J. Aggravating effect of INSIG2 and FTO on overweight reduction in a one-year lifestyle intervention. Arch Dis Child 2009.
[20]Rong R, Hanson RL, Ortiz D, et al. Association analysis of variation in/near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B with type 2 diabetes and related quantitative traits in Pima Indians. Diabetes 2009; 58:478-88.
[21]A1-Attar SA, Pollex RL, Ban MR, et al. Association between the FTO rs9939609 polymorphism and the metabolic syndrome in a non-Caucasian multi-ethnic sample. Cardiovasc Diabetol 2008; 7: 5.
[22]Gonzalez-Sanchez JL, Zabena C, Martinez-Larrad MT, Martinez-Calatrava MJ, Perez-Barba M, Serrano-Rios M. Variant rs9939609 in the FTO gene is associated with obesity in an adult population from Spain. Clin Endocrinol (Oxf) 2009; 70:390-3.
[23]Zimmermann E, Kring SI, Berentzen TL, et al. Fatness-associated FTO gene variant increases mortality independent of fatness--in cohorts of Danish men. PLoS ONE 2009; 4:e4428.
[24]Cha SW, Choi SM, Kim KS, Park BL, Kim JR, Kim JY, Shin HD. Replication of Genetic Effects of FTO Polymorphisms on BMI in a Korean Population. Obesity (Silver Spring) 2008.
[25]Chang YC, Liu PH, Lee WJ, et al. Common Variation in the FTO Gene Confers Risk of Obesity and Modulates Body Mass Index in the Chinese Population. Diabetes 2008.
[26]Hotta K, Nakata Y, Matsuo T, et al. Variations in the FTO gene are associated with severe obesity in the Japanese. J Hum Genet 2008; 53:546-53.
[27]Do R, Bailey SD, Desbiens K, et al. Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study. Diabetes 2008; 57:1147-50.
[28]Comes BK, Lind PA, Medland SE, Montgomery GW, Nyholt DR, Martin NG. Replication of the association of common rs9939609 variant of FTO with increased BMI in an Australian adult twin population but no evidence for gene by environment (G x E) interaction. Int J Obes (Lond) 2009; 33: 75-9.
[29]Li H, Wu Y, Loos RJ, et al. Variants in the fat mass- and obesity-associated (FTO) gene are not associated with obesity in a Chinese Han population. Diabetes 2008; 57:264-8.
[30]30 Hennig BJ, Fulford AJ, Sirugo G, Rayco-Solon P, Hattersley AT, Frayling TM, Prentice AM. FTO gene variation and measures of body mass in an Afr
[31]ican population. BMC Med Genet 2009; 10:21.
[32]Cauchi S, Stutzmann F, Cavalcanti-Proenca C, et al. Combined effects of MC4R and FTO common genetic variants on obesity in European general populations. J Mol Med 2009.
[33]Jess T, Zimmermann E, Kring SI, et al. Impact on weight dynamics and general growth of the common FTO rs9939609:a longitudinal Danish cohort study. Int J Obes (Lond) 2008; 32:1388-94.
[34]Lopez-Bermejo A, Petry CJ, Diaz M, Sebastiani G, de Zegher F, Dunger DB, Ibanez L. The association between the FTO gene and fat mass in humans develops by the postnatal age of two weeks. J Clin Endocrinol Metab 2008; 93:1501-5.
[35]Hakanen M, Raitakari OT, Lehtimaki T, et al. FTO Genotype Is Associated with Body Mass Index after the Age of 7 Years but Not with Energy Intake or Leisure-time Physical Activity. J Clin Endocrinol Metab 2009.
[36]Jacobsson JA, Danielsson P, Svensson V, et al. Major gender difference in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes. Biochem Biophys Res Commun 2008; 368:476-82.
[37]Rampersaud E, Mitchell BD, Pollin TI, et al. Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Intern Med 2008; 168:1791-7.
[38]Lappalainen TJ, Tolppanen AM, Kolehmainen M, et al. The Common Variant in the FTO Gene Did Not Modify the Effect of Lifestyle Changes on Body Weight:The Finnish Diabetes Prevention Study. Obesity (Silver Spring) 2009.
[39]Grant SF, Li M, Bradfield JP, et al. Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP. PLoS ONE 2008; 3:e1746.
[40]Haupt A, Thamer C, Machann J, et al. Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss. Obesity (Silver Spring) 2008; 16:1969-72.
[41]Muller TD, Hinney A, Scherag A, et al.'Fat mass and obesity associated' gene (FTO):no significant association of variant rs9939609 with weight loss in a lifestyle intervention and lipid metabolism markers in German obese children and adolescents. BMC Med Genet 2008; 9:85.
[42]Sanchez-Pulido L, Andrade-Navarro MA. The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamily. BMC Biochem 2007; 8:23.
[43]Jia G, Yang CG, Yang S, Jian X, Yi C, Zhou Z, He C. Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett 2008; 582:3313-9.
[44]Perry JR, Frayling TM. New gene variants alter type 2 diabetes risk predominantly through reduced beta-cell function. Curr Opin Clin Nutr Metab Care 2008; 11:371-7.
[45]Barber TM, Bennett AJ, Groves CJ, et al. Association of variants in the fat mass and obesity associated (FTO) gene with polycystic ovary syndrome. Diabetologia 2008; 51:1153-8.
[46]Badman MK, Flier JS. The gut and energy balance:visceral allies in the obesity wars. Science 2005; 307:1909-14.
[1]Leibowitz SF, Wortley KE. Hypothalamic control of energy balance:different peptides, different functions. Peptides 2004; 25:473-504.
[2]Badman MK, Flier JS. The gut and energy balance:visceral allies in the obesity wars. Science 2005; 307:1909-14.
[3]Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005; 184:291-318.
[4]Wilding JP. Neuropeptides and appetite control. Diabet Med 2002; 19:619-27.
[5]Nonaka N, Shioda S, Niehoff ML, Banks WA. Characterization of blood-brain barrier permeability to PYY3-36 in the mouse. J Pharmacol Exp Ther 2003; 306:948-53.
[6]Banks WA. The source of cerebral insulin. Eur J Pharmacol 2004; 490:5-12.
[7]Banks WA, Kastin AJ, Huang W, Jaspan JB, Maness LM. Leptin enters the brain by a saturable system independent of insulin. Peptides 1996; 17:305-11.
[8]Broberger C, Johansen J, Johansson C, Schalling M, Hokfelt T. The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proc Natl Acad Sci U S A 1998; 95:15043-8.
[9]Hahn TM, Breininger JF, Baskin DG, Schwartz MW. Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat Neurosci 1998; 1:271-2.
[10]Kristensen P, Judge ME, Thim L, et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 1998; 393:72-6.
[11]Elias CF, Aschkenasi C, Lee C, et al. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 1999; 23:775-86.
[12]Giraudo SQ, Billington CJ, Levine AS. Feeding effects of hypothalamic injection of melanocortin 4 receptor ligands. Brain Res 1998; 809:302-6.
[13]Guan XM, Yu H, Van der Ploeg LH. Evidence of altered hypothalamic pro-opiomelanocortin/ neuropeptide Y mRNA expression in tubby mice. Brain Res Mol Brain Res 1998; 59:273-9.
[14]Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 1999; 20:68-100.
[15]Sawchenko PE, Swanson LW. The organization and biochemical specificity of afferent projections to the paraventricular and supraoptic nuclei. Prog Brain Res 1983; 60:19-29.
[16]Hamamura M, Leng G, Emson PC, Kiyama H. Electrical activation and c-fos mRNA expression in rat neurosecretory neurones after systemic administration of cholecystokinin. J Physiol 1991; 444: 51-63.
[17]Zarjevski N, Cusin I, Vettor R, Rohner-Jeanrenaud F, Jeanrenaud B. Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity. Endocrinology 1993; 133:1753-8.
[18]Billington CJ, Briggs JE, Grace M, Levine AS. Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism. Am J Physiol 1991; 260:R321-7.
[19]Qian S, Chen H, Weingarth D, et al. Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Mol Cell Biol 2002; 22:5027-35.
[20]Chen P, Williams SM, Grove KL, Smith MS. Melanocortin 4 receptor-mediated hyperphagia and activation of neuropeptide Y expression in the dorsomedial hypothalamus during lactation. J Neurosci 2004; 24:5091-100.
[21]Huang XF, Han M, South T, Storlien L. Altered levels of POMC, AgRP and MC4-R mRNA expression in the hypothalamus and other parts of the limbic system of mice prone or resistant to chronic high-energy diet-induced obesity. Brain Res 2003; 992:9-19.
[22]Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318:1469-72.
[23]Fredriksson R, Hagglund M, Olszewski PK, et al. The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 2008; 149:2062-71.
[24]Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U. Inactivation of the Fto gene protects from obesity. Nature 2009.
[25]Berentzen T, Kring SI, Holst C, et al. Lack of Association of Fatness-Related FTO Gene Variants with Energy Expenditure or Physical Activity. J Clin Endocrinol Metab 2008; 93:2904-8.
[26]Haupt A, Thamer C, Staiger H, et al. Variation in the FTO Gene Influences Food Intake but not Energy Expenditure. Exp Clin Endocrinol Diabetes 2008.
[27]Hakanen M, Raitakari OT, Lehtimaki T, et al. FTO Genotype Is Associated with Body Mass Index after the Age of 7 Years but Not with Energy Intake or Leisure-time Physical Activity. J Clin Endocrinol Metab 2009.
[28]Stutzmann F, Cauchi S, Durand E, et al. Common genetic variation near MC4R is associated with eating behaviour patterns in European populations. Int J Obes (Lond) 2009.
[29]Do R, Bailey SD, Desbiens K, et al. Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study. Diabetes 2008; 57:1147-50.
[30]Johnson L, van Jaarsveld CH, Emmett PM, et al. Dietary energy density affects fat mass in early adolescence and is not modified by FTO variants. PLoS ONE 2009; 4:e4594.
[31]Wardle J, Carnell S, Haworth CM, Farooqi IS, O'Rahilly S, Plomin R. Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab 2008; 93:3640-3.
[32]Wardle J, Llewellyn C, Sanderson S, Plomin R. The FTO gene and measured food intake in children. Int J Obes (Lond) 2009; 33:42-5.
[33]Stratigopoulos G, Padilla SL, LeDuc CA, et al. Regulation of Fto/Ftm gene expression in mice and humans. Am J Physiol Regul Integr Comp Physiol 2008; 294:R1185-96.
[34]Villalobos-Comparan M, Teresa Flores-Dorantes M, Teresa Villarreal-Molina M, et al. The FTO gene is associated with adulthood obesity in the Mexican population. Obesity (Silver Spring) 2008; 16:2296-301.
[35]Jacobsson JA, Danielsson P, Svensson V, et al. Major gender difference in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes. Biochem Biophys Res Commun 2008; 368:476-82.
[36]Andreasen CH, Stender-Petersen KL, Mogensen MS, et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 2008; 57:95-101.
[37]Jacobsson JA, Klovins J, Kapa I, et al. Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents. Int J Obes (Lond) 2008; 32:1730-5.
[38]Tschritter O, Preissl H, Yokoyama Y, Machicao F, Haring HU, Fritsche A. Variation in the FTO gene locus is associated with cerebrocortical insulin resistance in humans. Diabetologia 2007; 50: 2602-3.
[39]Kloting N, Schleinitz D, Ruschke K, et al. Inverse relationship between obesity and FTO gene expression in visceral adipose tissue in humans. Diabetologia 2008; 51:641-7.
[40]Wahlen K, Sjolin E, Hoffstedt J. The common rs9939609 gene variant of the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis. J Lipid Res 2008; 49:607-11.
[41]Haupt A, Thamer C, Machann J, et al. Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss. Obesity (Silver Spring) 2008; 16:1969-72.
[42]Zabena C, Gonzalez-Sanchez JL, Martinez-Larrad MT, et al. The FTO obesity gene. Genotyping and gene expression analysis in morbidly obese patients. Obes Surg 2009; 19:87-95.
[43]Qi L, Kang K, Zhang C, et al. Fat mass-and obesity-associated (FTO) gene variant is associated with obesity:longitudinal analyses in two cohort studies and functional test. Diabetes 2008; 57: 3145-51.
[44]Fan B, Du ZQ, Rothschild MF. The fat mass and obesity-associated (FTO) gene is associated with intramuscular fat content and growth rate in the pig. Anim Biotechnol 2009; 20:58-70.
[45]Fontanesi L, Scotti E, Buttazzoni L, Davoli R, Russo V. The porcine fat mass and obesity associated (FTO) gene is associated with fat deposition in Italian Duroc pigs. Anim Genet 2009; 40: 90-3.
[46]Yuan L, Ni Y, Barth S, Wang Y, Grossmann R, Zhao R. Layer and broiler chicks exhibit similar hypothalamic expression of orexigenic neuropeptides but distinct expression of genes related to energy homeostasis and obesity. Brain Res 2009; 1273:18-28.
[47]Flier JS. Obesity wars:molecular progress confronts an expanding epidemic. Cell 2004; 116: 337-50.
[48]Taouis M, Chen JW, Daviaud C, Dupont J, Derouet M, Simon J. Cloning the chicken leptin gene. Gene 1998; 208:239-42.
[49]Bruggeman V OO, Decuypere E. Body weight, fat content, liver weight and plasma leptin concentrations in broiler breeder females reared under ad libitum feeding, restricted feeding or combinations of both until age of first egg. British Poultry Science 2000; 41:57-9.
[50]Schwartz MW, Seeley RJ, Woods SC, Weigle DS, Campfield LA, Burn P, Baskin DG. Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes 1997; 46:2119-23.
[51]Cowley MA, Smart JL, Rubinstein M, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 2001; 411:480-4.
[52]Seeley RJ, Yagaloff KA, Fisher SL, et al. Melanocortin receptors in leptin effects. Nature 1997; 390: 349.
[53]Dridi S, Swennen Q, Decuypere E, Buyse J. Mode of leptin action in chicken hypothalamus. Brain Res 2005; 1047:214-23.
[54]Schwartz MW, Sipols AJ, Marks JL, et al. Inhibition of hypothalamic neuropeptide Y gene expression by insulin. Endocrinology 1992; 130:3608-16.
[55]Benoit SC, Air EL, Coolen LM, et al. The catabolic action of insulin in the brain is mediated by melanocortins. J Neurosci 2002; 22:9048-52.
[56]Honda K, Kamisoyama H, Saneyasu T, Sugahara K, Hasegawa S. Central administration of insulin suppresses food intake in chicks. Neurosci Lett 2007; 423:153-7.
[57]Tachibana T, Sugahara K, Ohgushi A, Ando R, Kawakami S, Yoshimatsu T, Furuse M. Intracerebroventricular injection of agouti-related protein attenuates the anorexigenic effect of alpha-melanocyte stimulating hormone in neonatal chicks. Neurosci Lett 2001; 305:131-4.
[58]Hen G, Yosefi S, Simchaev V, Shinder D, Hruby VJ, Friedman-Einat M. The melanocortin circuit in obese and lean strains of chicks. J Endocrinol 2006; 190:527-35.
[1]Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316:889-94.
[2]Fredriksson R, Hagglund M, Olszewski PK, et al. The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 2008; 149:2062-71.
[3]Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318:1469-72.
[4]Qi L, Kang K, Zhang C, et al. Fat mass-and obesity-associated (FTO) gene variant is associated with obesity:longitudinal analyses in two cohort studies and functional test. Diabetes 2008; 57: 3145-51.
[5]Stratigopoulos G, Padilla SL, LeDuc CA, et al. Regulation of Fto/Ftm gene expression in mice and humans. Am J Physiol Regul Integr Comp Physiol 2008; 294:R1185-96.
[6]Willer CJ, Speliotes EK, Loos RJ, et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009; 41:25-34.
[7]Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987; 162:156-9.
[8]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25:402-8.
[9]Yuan L, Ni Y, Barth S, Wang Y, Grossmann R, Zhao R. Layer and broiler chicks exhibit similar hypothalamic expression of orexigenic neuropeptides but distinct expression of genes related to energy homeostasis and obesity. Brain Res 2009; 1273:18-28.
[10]Badman MK, Flier JS. The gut and energy balance:visceral allies in the obesity wars. Science 2005; 307:1909-14.
[11]Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005; 184:291-318.
[12]Bruggeman V OO, Decuypere E. Body weight, fat content, liver weight and plasma leptin concentrations in broiler breeder females reared under ad libitum feeding, restricted feeding or combinations of both until age of first egg. British Poultry Science 2000; 41:57-9.
[13]Taouis M, Chen JW, Daviaud C, Dupont J, Derouet M, Simon J. Cloning the chicken leptin gene. Gene 1998; 208:239-42.
[14]Taouis M, Dridi S, Cassy S, et al. Chicken leptin:properties and actions. Domest Anim Endocrinol 2001; 21:319-27.
[15]Cavdar S, San T, Aker R, Sehirli U, Onat F. Cerebellar connections to the dorsomedial and posterior nuclei of the hypothalamus in the rat. J Anat 2001; 198:37-45.
[16]Zhu JN, Zhang YP, Song YN, Wang JJ. Cerebellar interpositus nuclear and gastric vagal afferent inputs reach and converge onto glycemia-sensitive neurons of the ventromedial hypothalamic nucleus in rats. Neurosci Res 2004; 48:405-17.
[17]Do R, Bailey SD, Desbiens K, et al. Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study. Diabetes 2008; 57:1147-50.
[18]Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U. Inactivation of the Fto gene protects from obesity. Nature 2009.
[19]Kloting N, Schleinitz D, Ruschke K, et al. Inverse relationship between obesity and FTO gene expression in visceral adipose tissue in humans. Diabetologia 2008; 51:641-7.
[20]Wajchenberg BL. Subcutaneous and visceral adipose tissue:their relation to the metabolic syndrome. Endocr Rev 2000; 21:697-738.
[21]Klein S, Fontana L, Young VL, Coggan AR, Kilo C, Patterson BW, Mohammed BS. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med 2004; 350:2549-57.
[22]Thorne A, Lonnqvist F, Apelman J, Hellers G, Arner P. A pilot study of long-term effects of a novel obesity treatment:omentectomy in connection with adjustable gastric banding. Int J Obes Relat Metab Disord 2002; 26:193-9.
[23]Manchanda SK, Tandon OP, Aneja IS. Role of the cerebellum in the control of gastro-intestinal motility. J Neural Transm 1972; 33:195-209.
[24]Cassy S, Picard M, Crochet S, Derouet M, Keisler DH, Taouis M. Peripheral leptin effect on food intake in young chickens is influenced by age and strain. Domest Anim Endocrinol 2004; 27: 51-61.
[1]Fredriksson R, Hagglund M, Olszewski PK, et al. The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 2008; 149:2062-71.
[2]Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318:1469-72.
[3]Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U. Inactivation of the Fto gene protects from obesity. Nature 2009.
[4]Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005; 184:291-318.
[5]Guan XM, Yu H, Van der Ploeg LH. Evidence of altered hypothalamic pro-opiomelanocortin/ neuropeptide Y mRNA expression in tubby mice. Brain Res Mol Brain Res 1998; 59:273-9.
[6]Kuenzel WJ. Transient aphagia produced following bilateral destruction of the lateral hypothalamic area and quinto-frontal tract of chicks. Physiol Behav 1982; 28:237-44.
[7]Gentle MJ. Using arousal changes in the EEG to indicate gustatory sensitivity following brain lesion in Gallus domesticus. Br Poult Sci 1976; 17:151-6.
[8]Miceli D, Reperant J, Ward R, Rio JP, Jay B, Medina M, Kenigfest NB. Fine structure of the visual dorsolateral anterior thalamic nucleus of the pigeon (Columba livia):a hodological and GABA-immunocytochemical study. J Comp Neurol 2008; 507:1351-78.
[9]Sebesteny T, Tombol T. The Golgi architecture and some EM observations on the avian nucleus dorsolateralis anterior thalami:cell types, fibres and synapses. Ann Anat 1998; 180:97-111.
[10]Dubbeldam JL, den Boer-Visser AM, Bout RG. Organization and efferent connections of the archistriatum of the mallard, Anas platyrhynchos L.:an anterograde and retrograde tracing study. J Comp Neurol 1997; 388:632-57.
[11]Horowitz SS, Blanchard JH, Morin LP. Intergeniculate leaflet and ventral lateral geniculate nucleus afferent connections:An anatomical substrate for functional input from the vestibulo-visuomotor system. J Comp Neurol 2004; 474:227-45.
[12]Morcuende S, Delgado-Garcia JM, Ugolini G. Neuronal premotor networks involved in eyelid responses:retrograde transneuronal tracing with rabies virus from the orbicularis oculi muscle in the rat. J Neurosci 2002; 22:8808-18.
[13]Sartsoongnoen N, Kosonsiriluk S, Prakobsaeng N, Songserm T, Rozenboim I, Halawani ME, Chaiseha Y. The dopaminergic system in the brain of the native Thai chicken, Gallus domesticus: localization and differential expression across the reproductive cycle. Gen Comp Endocrinol 2008; 159:107-15.
[1]Leibowitz SF, Wortley KE. Hypothalamic control of energy balance:different peptides, different functions. Peptides 2004; 25:473-504.
[2]Badman MK, Flier JS. The gut and energy balance:visceral allies in the obesity wars. Science 2005; 307:1909-14.
[3]Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005; 184:291-318.
[4]Guan XM, Yu H, Van der Ploeg LH. Evidence of altered hypothalamic pro-opiomelanocortin/ neuropeptide Y mRNA expression in tubby mice. Brain Res Mol Brain Res 1998; 59:273-9.
[5]Sawchenko PE, Swanson LW. The organization and biochemical specificity of afferent projections to the paraventricular and supraoptic nuclei. Prog Brain Res 1983; 60:19-29.
[6]Hamamura M, Leng G, Emson PC, Kiyama H. Electrical activation and c-fos mRNA expression in rat neurosecretory neurones after systemic administration of cholecystokinin. J Physiol 1991; 444: 51-63.
[7]Zarjevski N, Cusin I, Vettor R, Rohner-Jeanrenaud F, Jeanrenaud B. Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity. Endocrinology 1993; 133:1753-8.
[8]Billington CJ, Briggs JE, Grace M, Levine AS. Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism. Am J Physiol 1991; 260:R321-7.
[9]Qian S, Chen H, Weingarth D, et al. Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Mol Cell Biol 2002; 22:5027-35.
[10]Huang XF, Han M, South T, Storlien L. Altered levels of POMC, AgRP and MC4-R mRNA expression in the hypothalamus and other parts of the limbic system of mice prone or resistant to chronic high-energy diet-induced obesity. Brain Res 2003; 992:9-19.
[11]Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318:1469-72.
[12]Hen G, Yosefi S, Simchaev V, Shinder D, Hruby VJ, Friedman-Einat M. The melanocortin circuit in obese and lean strains of chicks. J Endocrinol 2006; 190:527-35.
[13]Tachibana T, Sugahara K, Ohgushi A, Ando R, Kawakami S, Yoshimatsu T, Furuse M. Intracerebroventricular injection of agouti-related protein attenuates the anorexigenic effect of alpha-melanocyte stimulating hormone in neonatal chicks. Neurosci Lett 2001; 305:131-4.
[2]van der Hoeven F, Schimmang T, Volkmann A, Mattei MG, Kyewski B, Ruther U. Programmed cell death is affected in the novel mouse mutant Fused toes (Ft). Development 1994; 120:2601-7.
[3]Heymer J, Kuehn M, Ruther U. The expression pattern of nodal and lefty in the mouse mutant Ft suggests a function in the establishment of handedness. Mech Dev 1997; 66:5-11.
[4]Peters T, Ausmeier K, Dildrop R, Ruther U. The mouse Fused toes (Ft) mutation is the result of a 1.6-Mb deletion including the entire Iroquois B gene cluster. Mamm Genome 2002; 13:186-8.
[5]Peters T, Ausmeier K, Ruther U. Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation. Mamm Genome 1999; 10:983-6.
[6]Robbens S, Rouze P, Cock JM, Spring J, Worden AZ, Van de Peer Y. The FTO gene, implicated in human obesity, is found only in vertebrates and marine algae. J Mol Evol 2008; 66:80-4.
[7]Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316:889-94.
[8]Fredriksson R, Hagglund M, Olszewski PK, et al. The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 2008; 149:2062-71.
[9]Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318:1469-72.
[10]Dina C, Meyre D, Gallina S, et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 2007; 39:724-6.
[11]Scuteri A, Sanna S, Chen WM, et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007; 3:e115.
[12]Qi L, Kang K, Zhang C, et al. Fat mass-and obesity-associated (FTO) gene variant is associated with obesity:longitudinal analyses in two cohort studies and functional test. Diabetes 2008; 57: 3145-51.
[13]Stratigopoulos G, Padilla SL, LeDuc CA, et al. Regulation of Fto/Ftm gene expression in mice and humans. Am J Physiol Regul Integr Comp Physiol 2008; 294:R1185-96.
[14]Willer CJ, Speliotes EK, Loos RJ, et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009; 41:25-34.
[15]Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U. Inactivation of the Fto gene protects from obesity. Nature 2009.
[16]Horowitz SS, Blanchard JH, Morin LP. Intergeniculate leaflet and ventral lateral geniculate nucleus afferent connections:An anatomical substrate for functional input from the vestibulo-visuomotor system. J Comp Neurol 2004; 474:227-45.
[17]Hinney A, Nguyen TT, Scherag A, et al. Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS ONE 2007;2:e1361.
[18]Andreasen CH, Stender-Petersen KL, Mogensen MS, et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 2008; 57:95-101.
[19]Reinehr T, Hinney A, Toschke AM, Hebebrand J. Aggravating effect of INSIG2 and FTO on overweight reduction in a one-year lifestyle intervention. Arch Dis Child 2009.
[20]Rong R, Hanson RL, Ortiz D, et al. Association analysis of variation in/near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B with type 2 diabetes and related quantitative traits in Pima Indians. Diabetes 2009; 58:478-88.
[21]A1-Attar SA, Pollex RL, Ban MR, et al. Association between the FTO rs9939609 polymorphism and the metabolic syndrome in a non-Caucasian multi-ethnic sample. Cardiovasc Diabetol 2008; 7: 5.
[22]Gonzalez-Sanchez JL, Zabena C, Martinez-Larrad MT, Martinez-Calatrava MJ, Perez-Barba M, Serrano-Rios M. Variant rs9939609 in the FTO gene is associated with obesity in an adult population from Spain. Clin Endocrinol (Oxf) 2009; 70:390-3.
[23]Zimmermann E, Kring SI, Berentzen TL, et al. Fatness-associated FTO gene variant increases mortality independent of fatness--in cohorts of Danish men. PLoS ONE 2009; 4:e4428.
[24]Cha SW, Choi SM, Kim KS, Park BL, Kim JR, Kim JY, Shin HD. Replication of Genetic Effects of FTO Polymorphisms on BMI in a Korean Population. Obesity (Silver Spring) 2008.
[25]Chang YC, Liu PH, Lee WJ, et al. Common Variation in the FTO Gene Confers Risk of Obesity and Modulates Body Mass Index in the Chinese Population. Diabetes 2008.
[26]Hotta K, Nakata Y, Matsuo T, et al. Variations in the FTO gene are associated with severe obesity in the Japanese. J Hum Genet 2008; 53:546-53.
[27]Do R, Bailey SD, Desbiens K, et al. Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study. Diabetes 2008; 57:1147-50.
[28]Comes BK, Lind PA, Medland SE, Montgomery GW, Nyholt DR, Martin NG. Replication of the association of common rs9939609 variant of FTO with increased BMI in an Australian adult twin population but no evidence for gene by environment (G x E) interaction. Int J Obes (Lond) 2009; 33: 75-9.
[29]Li H, Wu Y, Loos RJ, et al. Variants in the fat mass- and obesity-associated (FTO) gene are not associated with obesity in a Chinese Han population. Diabetes 2008; 57:264-8.
[30]30 Hennig BJ, Fulford AJ, Sirugo G, Rayco-Solon P, Hattersley AT, Frayling TM, Prentice AM. FTO gene variation and measures of body mass in an Afr
[31]ican population. BMC Med Genet 2009; 10:21.
[32]Cauchi S, Stutzmann F, Cavalcanti-Proenca C, et al. Combined effects of MC4R and FTO common genetic variants on obesity in European general populations. J Mol Med 2009.
[33]Jess T, Zimmermann E, Kring SI, et al. Impact on weight dynamics and general growth of the common FTO rs9939609:a longitudinal Danish cohort study. Int J Obes (Lond) 2008; 32:1388-94.
[34]Lopez-Bermejo A, Petry CJ, Diaz M, Sebastiani G, de Zegher F, Dunger DB, Ibanez L. The association between the FTO gene and fat mass in humans develops by the postnatal age of two weeks. J Clin Endocrinol Metab 2008; 93:1501-5.
[35]Hakanen M, Raitakari OT, Lehtimaki T, et al. FTO Genotype Is Associated with Body Mass Index after the Age of 7 Years but Not with Energy Intake or Leisure-time Physical Activity. J Clin Endocrinol Metab 2009.
[36]Jacobsson JA, Danielsson P, Svensson V, et al. Major gender difference in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes. Biochem Biophys Res Commun 2008; 368:476-82.
[37]Rampersaud E, Mitchell BD, Pollin TI, et al. Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Intern Med 2008; 168:1791-7.
[38]Lappalainen TJ, Tolppanen AM, Kolehmainen M, et al. The Common Variant in the FTO Gene Did Not Modify the Effect of Lifestyle Changes on Body Weight:The Finnish Diabetes Prevention Study. Obesity (Silver Spring) 2009.
[39]Grant SF, Li M, Bradfield JP, et al. Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP. PLoS ONE 2008; 3:e1746.
[40]Haupt A, Thamer C, Machann J, et al. Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss. Obesity (Silver Spring) 2008; 16:1969-72.
[41]Muller TD, Hinney A, Scherag A, et al.'Fat mass and obesity associated' gene (FTO):no significant association of variant rs9939609 with weight loss in a lifestyle intervention and lipid metabolism markers in German obese children and adolescents. BMC Med Genet 2008; 9:85.
[42]Sanchez-Pulido L, Andrade-Navarro MA. The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamily. BMC Biochem 2007; 8:23.
[43]Jia G, Yang CG, Yang S, Jian X, Yi C, Zhou Z, He C. Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett 2008; 582:3313-9.
[44]Perry JR, Frayling TM. New gene variants alter type 2 diabetes risk predominantly through reduced beta-cell function. Curr Opin Clin Nutr Metab Care 2008; 11:371-7.
[45]Barber TM, Bennett AJ, Groves CJ, et al. Association of variants in the fat mass and obesity associated (FTO) gene with polycystic ovary syndrome. Diabetologia 2008; 51:1153-8.
[46]Badman MK, Flier JS. The gut and energy balance:visceral allies in the obesity wars. Science 2005; 307:1909-14.
[1]Leibowitz SF, Wortley KE. Hypothalamic control of energy balance:different peptides, different functions. Peptides 2004; 25:473-504.
[2]Badman MK, Flier JS. The gut and energy balance:visceral allies in the obesity wars. Science 2005; 307:1909-14.
[3]Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005; 184:291-318.
[4]Wilding JP. Neuropeptides and appetite control. Diabet Med 2002; 19:619-27.
[5]Nonaka N, Shioda S, Niehoff ML, Banks WA. Characterization of blood-brain barrier permeability to PYY3-36 in the mouse. J Pharmacol Exp Ther 2003; 306:948-53.
[6]Banks WA. The source of cerebral insulin. Eur J Pharmacol 2004; 490:5-12.
[7]Banks WA, Kastin AJ, Huang W, Jaspan JB, Maness LM. Leptin enters the brain by a saturable system independent of insulin. Peptides 1996; 17:305-11.
[8]Broberger C, Johansen J, Johansson C, Schalling M, Hokfelt T. The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proc Natl Acad Sci U S A 1998; 95:15043-8.
[9]Hahn TM, Breininger JF, Baskin DG, Schwartz MW. Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat Neurosci 1998; 1:271-2.
[10]Kristensen P, Judge ME, Thim L, et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 1998; 393:72-6.
[11]Elias CF, Aschkenasi C, Lee C, et al. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 1999; 23:775-86.
[12]Giraudo SQ, Billington CJ, Levine AS. Feeding effects of hypothalamic injection of melanocortin 4 receptor ligands. Brain Res 1998; 809:302-6.
[13]Guan XM, Yu H, Van der Ploeg LH. Evidence of altered hypothalamic pro-opiomelanocortin/ neuropeptide Y mRNA expression in tubby mice. Brain Res Mol Brain Res 1998; 59:273-9.
[14]Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 1999; 20:68-100.
[15]Sawchenko PE, Swanson LW. The organization and biochemical specificity of afferent projections to the paraventricular and supraoptic nuclei. Prog Brain Res 1983; 60:19-29.
[16]Hamamura M, Leng G, Emson PC, Kiyama H. Electrical activation and c-fos mRNA expression in rat neurosecretory neurones after systemic administration of cholecystokinin. J Physiol 1991; 444: 51-63.
[17]Zarjevski N, Cusin I, Vettor R, Rohner-Jeanrenaud F, Jeanrenaud B. Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity. Endocrinology 1993; 133:1753-8.
[18]Billington CJ, Briggs JE, Grace M, Levine AS. Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism. Am J Physiol 1991; 260:R321-7.
[19]Qian S, Chen H, Weingarth D, et al. Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Mol Cell Biol 2002; 22:5027-35.
[20]Chen P, Williams SM, Grove KL, Smith MS. Melanocortin 4 receptor-mediated hyperphagia and activation of neuropeptide Y expression in the dorsomedial hypothalamus during lactation. J Neurosci 2004; 24:5091-100.
[21]Huang XF, Han M, South T, Storlien L. Altered levels of POMC, AgRP and MC4-R mRNA expression in the hypothalamus and other parts of the limbic system of mice prone or resistant to chronic high-energy diet-induced obesity. Brain Res 2003; 992:9-19.
[22]Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318:1469-72.
[23]Fredriksson R, Hagglund M, Olszewski PK, et al. The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 2008; 149:2062-71.
[24]Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U. Inactivation of the Fto gene protects from obesity. Nature 2009.
[25]Berentzen T, Kring SI, Holst C, et al. Lack of Association of Fatness-Related FTO Gene Variants with Energy Expenditure or Physical Activity. J Clin Endocrinol Metab 2008; 93:2904-8.
[26]Haupt A, Thamer C, Staiger H, et al. Variation in the FTO Gene Influences Food Intake but not Energy Expenditure. Exp Clin Endocrinol Diabetes 2008.
[27]Hakanen M, Raitakari OT, Lehtimaki T, et al. FTO Genotype Is Associated with Body Mass Index after the Age of 7 Years but Not with Energy Intake or Leisure-time Physical Activity. J Clin Endocrinol Metab 2009.
[28]Stutzmann F, Cauchi S, Durand E, et al. Common genetic variation near MC4R is associated with eating behaviour patterns in European populations. Int J Obes (Lond) 2009.
[29]Do R, Bailey SD, Desbiens K, et al. Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study. Diabetes 2008; 57:1147-50.
[30]Johnson L, van Jaarsveld CH, Emmett PM, et al. Dietary energy density affects fat mass in early adolescence and is not modified by FTO variants. PLoS ONE 2009; 4:e4594.
[31]Wardle J, Carnell S, Haworth CM, Farooqi IS, O'Rahilly S, Plomin R. Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab 2008; 93:3640-3.
[32]Wardle J, Llewellyn C, Sanderson S, Plomin R. The FTO gene and measured food intake in children. Int J Obes (Lond) 2009; 33:42-5.
[33]Stratigopoulos G, Padilla SL, LeDuc CA, et al. Regulation of Fto/Ftm gene expression in mice and humans. Am J Physiol Regul Integr Comp Physiol 2008; 294:R1185-96.
[34]Villalobos-Comparan M, Teresa Flores-Dorantes M, Teresa Villarreal-Molina M, et al. The FTO gene is associated with adulthood obesity in the Mexican population. Obesity (Silver Spring) 2008; 16:2296-301.
[35]Jacobsson JA, Danielsson P, Svensson V, et al. Major gender difference in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes. Biochem Biophys Res Commun 2008; 368:476-82.
[36]Andreasen CH, Stender-Petersen KL, Mogensen MS, et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 2008; 57:95-101.
[37]Jacobsson JA, Klovins J, Kapa I, et al. Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents. Int J Obes (Lond) 2008; 32:1730-5.
[38]Tschritter O, Preissl H, Yokoyama Y, Machicao F, Haring HU, Fritsche A. Variation in the FTO gene locus is associated with cerebrocortical insulin resistance in humans. Diabetologia 2007; 50: 2602-3.
[39]Kloting N, Schleinitz D, Ruschke K, et al. Inverse relationship between obesity and FTO gene expression in visceral adipose tissue in humans. Diabetologia 2008; 51:641-7.
[40]Wahlen K, Sjolin E, Hoffstedt J. The common rs9939609 gene variant of the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis. J Lipid Res 2008; 49:607-11.
[41]Haupt A, Thamer C, Machann J, et al. Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss. Obesity (Silver Spring) 2008; 16:1969-72.
[42]Zabena C, Gonzalez-Sanchez JL, Martinez-Larrad MT, et al. The FTO obesity gene. Genotyping and gene expression analysis in morbidly obese patients. Obes Surg 2009; 19:87-95.
[43]Qi L, Kang K, Zhang C, et al. Fat mass-and obesity-associated (FTO) gene variant is associated with obesity:longitudinal analyses in two cohort studies and functional test. Diabetes 2008; 57: 3145-51.
[44]Fan B, Du ZQ, Rothschild MF. The fat mass and obesity-associated (FTO) gene is associated with intramuscular fat content and growth rate in the pig. Anim Biotechnol 2009; 20:58-70.
[45]Fontanesi L, Scotti E, Buttazzoni L, Davoli R, Russo V. The porcine fat mass and obesity associated (FTO) gene is associated with fat deposition in Italian Duroc pigs. Anim Genet 2009; 40: 90-3.
[46]Yuan L, Ni Y, Barth S, Wang Y, Grossmann R, Zhao R. Layer and broiler chicks exhibit similar hypothalamic expression of orexigenic neuropeptides but distinct expression of genes related to energy homeostasis and obesity. Brain Res 2009; 1273:18-28.
[47]Flier JS. Obesity wars:molecular progress confronts an expanding epidemic. Cell 2004; 116: 337-50.
[48]Taouis M, Chen JW, Daviaud C, Dupont J, Derouet M, Simon J. Cloning the chicken leptin gene. Gene 1998; 208:239-42.
[49]Bruggeman V OO, Decuypere E. Body weight, fat content, liver weight and plasma leptin concentrations in broiler breeder females reared under ad libitum feeding, restricted feeding or combinations of both until age of first egg. British Poultry Science 2000; 41:57-9.
[50]Schwartz MW, Seeley RJ, Woods SC, Weigle DS, Campfield LA, Burn P, Baskin DG. Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes 1997; 46:2119-23.
[51]Cowley MA, Smart JL, Rubinstein M, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 2001; 411:480-4.
[52]Seeley RJ, Yagaloff KA, Fisher SL, et al. Melanocortin receptors in leptin effects. Nature 1997; 390: 349.
[53]Dridi S, Swennen Q, Decuypere E, Buyse J. Mode of leptin action in chicken hypothalamus. Brain Res 2005; 1047:214-23.
[54]Schwartz MW, Sipols AJ, Marks JL, et al. Inhibition of hypothalamic neuropeptide Y gene expression by insulin. Endocrinology 1992; 130:3608-16.
[55]Benoit SC, Air EL, Coolen LM, et al. The catabolic action of insulin in the brain is mediated by melanocortins. J Neurosci 2002; 22:9048-52.
[56]Honda K, Kamisoyama H, Saneyasu T, Sugahara K, Hasegawa S. Central administration of insulin suppresses food intake in chicks. Neurosci Lett 2007; 423:153-7.
[57]Tachibana T, Sugahara K, Ohgushi A, Ando R, Kawakami S, Yoshimatsu T, Furuse M. Intracerebroventricular injection of agouti-related protein attenuates the anorexigenic effect of alpha-melanocyte stimulating hormone in neonatal chicks. Neurosci Lett 2001; 305:131-4.
[58]Hen G, Yosefi S, Simchaev V, Shinder D, Hruby VJ, Friedman-Einat M. The melanocortin circuit in obese and lean strains of chicks. J Endocrinol 2006; 190:527-35.
[1]Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316:889-94.
[2]Fredriksson R, Hagglund M, Olszewski PK, et al. The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 2008; 149:2062-71.
[3]Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318:1469-72.
[4]Qi L, Kang K, Zhang C, et al. Fat mass-and obesity-associated (FTO) gene variant is associated with obesity:longitudinal analyses in two cohort studies and functional test. Diabetes 2008; 57: 3145-51.
[5]Stratigopoulos G, Padilla SL, LeDuc CA, et al. Regulation of Fto/Ftm gene expression in mice and humans. Am J Physiol Regul Integr Comp Physiol 2008; 294:R1185-96.
[6]Willer CJ, Speliotes EK, Loos RJ, et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009; 41:25-34.
[7]Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987; 162:156-9.
[8]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25:402-8.
[9]Yuan L, Ni Y, Barth S, Wang Y, Grossmann R, Zhao R. Layer and broiler chicks exhibit similar hypothalamic expression of orexigenic neuropeptides but distinct expression of genes related to energy homeostasis and obesity. Brain Res 2009; 1273:18-28.
[10]Badman MK, Flier JS. The gut and energy balance:visceral allies in the obesity wars. Science 2005; 307:1909-14.
[11]Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005; 184:291-318.
[12]Bruggeman V OO, Decuypere E. Body weight, fat content, liver weight and plasma leptin concentrations in broiler breeder females reared under ad libitum feeding, restricted feeding or combinations of both until age of first egg. British Poultry Science 2000; 41:57-9.
[13]Taouis M, Chen JW, Daviaud C, Dupont J, Derouet M, Simon J. Cloning the chicken leptin gene. Gene 1998; 208:239-42.
[14]Taouis M, Dridi S, Cassy S, et al. Chicken leptin:properties and actions. Domest Anim Endocrinol 2001; 21:319-27.
[15]Cavdar S, San T, Aker R, Sehirli U, Onat F. Cerebellar connections to the dorsomedial and posterior nuclei of the hypothalamus in the rat. J Anat 2001; 198:37-45.
[16]Zhu JN, Zhang YP, Song YN, Wang JJ. Cerebellar interpositus nuclear and gastric vagal afferent inputs reach and converge onto glycemia-sensitive neurons of the ventromedial hypothalamic nucleus in rats. Neurosci Res 2004; 48:405-17.
[17]Do R, Bailey SD, Desbiens K, et al. Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study. Diabetes 2008; 57:1147-50.
[18]Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U. Inactivation of the Fto gene protects from obesity. Nature 2009.
[19]Kloting N, Schleinitz D, Ruschke K, et al. Inverse relationship between obesity and FTO gene expression in visceral adipose tissue in humans. Diabetologia 2008; 51:641-7.
[20]Wajchenberg BL. Subcutaneous and visceral adipose tissue:their relation to the metabolic syndrome. Endocr Rev 2000; 21:697-738.
[21]Klein S, Fontana L, Young VL, Coggan AR, Kilo C, Patterson BW, Mohammed BS. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med 2004; 350:2549-57.
[22]Thorne A, Lonnqvist F, Apelman J, Hellers G, Arner P. A pilot study of long-term effects of a novel obesity treatment:omentectomy in connection with adjustable gastric banding. Int J Obes Relat Metab Disord 2002; 26:193-9.
[23]Manchanda SK, Tandon OP, Aneja IS. Role of the cerebellum in the control of gastro-intestinal motility. J Neural Transm 1972; 33:195-209.
[24]Cassy S, Picard M, Crochet S, Derouet M, Keisler DH, Taouis M. Peripheral leptin effect on food intake in young chickens is influenced by age and strain. Domest Anim Endocrinol 2004; 27: 51-61.
[1]Fredriksson R, Hagglund M, Olszewski PK, et al. The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 2008; 149:2062-71.
[2]Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318:1469-72.
[3]Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U. Inactivation of the Fto gene protects from obesity. Nature 2009.
[4]Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005; 184:291-318.
[5]Guan XM, Yu H, Van der Ploeg LH. Evidence of altered hypothalamic pro-opiomelanocortin/ neuropeptide Y mRNA expression in tubby mice. Brain Res Mol Brain Res 1998; 59:273-9.
[6]Kuenzel WJ. Transient aphagia produced following bilateral destruction of the lateral hypothalamic area and quinto-frontal tract of chicks. Physiol Behav 1982; 28:237-44.
[7]Gentle MJ. Using arousal changes in the EEG to indicate gustatory sensitivity following brain lesion in Gallus domesticus. Br Poult Sci 1976; 17:151-6.
[8]Miceli D, Reperant J, Ward R, Rio JP, Jay B, Medina M, Kenigfest NB. Fine structure of the visual dorsolateral anterior thalamic nucleus of the pigeon (Columba livia):a hodological and GABA-immunocytochemical study. J Comp Neurol 2008; 507:1351-78.
[9]Sebesteny T, Tombol T. The Golgi architecture and some EM observations on the avian nucleus dorsolateralis anterior thalami:cell types, fibres and synapses. Ann Anat 1998; 180:97-111.
[10]Dubbeldam JL, den Boer-Visser AM, Bout RG. Organization and efferent connections of the archistriatum of the mallard, Anas platyrhynchos L.:an anterograde and retrograde tracing study. J Comp Neurol 1997; 388:632-57.
[11]Horowitz SS, Blanchard JH, Morin LP. Intergeniculate leaflet and ventral lateral geniculate nucleus afferent connections:An anatomical substrate for functional input from the vestibulo-visuomotor system. J Comp Neurol 2004; 474:227-45.
[12]Morcuende S, Delgado-Garcia JM, Ugolini G. Neuronal premotor networks involved in eyelid responses:retrograde transneuronal tracing with rabies virus from the orbicularis oculi muscle in the rat. J Neurosci 2002; 22:8808-18.
[13]Sartsoongnoen N, Kosonsiriluk S, Prakobsaeng N, Songserm T, Rozenboim I, Halawani ME, Chaiseha Y. The dopaminergic system in the brain of the native Thai chicken, Gallus domesticus: localization and differential expression across the reproductive cycle. Gen Comp Endocrinol 2008; 159:107-15.
[1]Leibowitz SF, Wortley KE. Hypothalamic control of energy balance:different peptides, different functions. Peptides 2004; 25:473-504.
[2]Badman MK, Flier JS. The gut and energy balance:visceral allies in the obesity wars. Science 2005; 307:1909-14.
[3]Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005; 184:291-318.
[4]Guan XM, Yu H, Van der Ploeg LH. Evidence of altered hypothalamic pro-opiomelanocortin/ neuropeptide Y mRNA expression in tubby mice. Brain Res Mol Brain Res 1998; 59:273-9.
[5]Sawchenko PE, Swanson LW. The organization and biochemical specificity of afferent projections to the paraventricular and supraoptic nuclei. Prog Brain Res 1983; 60:19-29.
[6]Hamamura M, Leng G, Emson PC, Kiyama H. Electrical activation and c-fos mRNA expression in rat neurosecretory neurones after systemic administration of cholecystokinin. J Physiol 1991; 444: 51-63.
[7]Zarjevski N, Cusin I, Vettor R, Rohner-Jeanrenaud F, Jeanrenaud B. Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity. Endocrinology 1993; 133:1753-8.
[8]Billington CJ, Briggs JE, Grace M, Levine AS. Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism. Am J Physiol 1991; 260:R321-7.
[9]Qian S, Chen H, Weingarth D, et al. Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Mol Cell Biol 2002; 22:5027-35.
[10]Huang XF, Han M, South T, Storlien L. Altered levels of POMC, AgRP and MC4-R mRNA expression in the hypothalamus and other parts of the limbic system of mice prone or resistant to chronic high-energy diet-induced obesity. Brain Res 2003; 992:9-19.
[11]Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318:1469-72.
[12]Hen G, Yosefi S, Simchaev V, Shinder D, Hruby VJ, Friedman-Einat M. The melanocortin circuit in obese and lean strains of chicks. J Endocrinol 2006; 190:527-35.
[13]Tachibana T, Sugahara K, Ohgushi A, Ando R, Kawakami S, Yoshimatsu T, Furuse M. Intracerebroventricular injection of agouti-related protein attenuates the anorexigenic effect of alpha-melanocyte stimulating hormone in neonatal chicks. Neurosci Lett 2001; 305:131-4.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |