营养状态影响大鼠味蕾甘丙肽及其受体mRNA的表达
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摘要
机体的营养代谢状态参与调制外周味觉信息的整合,影响外周味觉感受和食物摄入。味蕾上的味觉受体及神经递质都是营养状态调节味觉感知的重要靶点。本文旨在探讨营养状态对味蕾上的重要神经递质甘丙肽及其受体表达的影响。我们比较了高脂饮食诱导的肥胖大鼠、慢性限制性饮食大鼠、以及正常膳食大鼠味蕾水平甘丙肽及其受体2 (galanin receptor 2,GalR2)mRNA表达水平的差异,以探讨机体营养代谢状态是否通过调控味蕾水平甘丙肽的表达来影响味觉感知。分别给予各组大鼠6周的高脂饮食、半量饮食和正常饮食,检测其体重、血糖、血脂等代谢相关指标,用real-time PCR方法检测其味蕾甘丙肽与GalR2 mRNA的表达变化。结果显示:与对照组相比,高脂饮食大鼠的体重显著增加,血清甘油三酯及血糖水平显著增高,味蕾水平甘丙肽与GalR2的mRNA表达水平显著降低,而慢性限制性饮食大鼠味蕾甘丙肽的mRNA表达增高,是对照组的2.3倍。结合以前的研究,我们可以得出初步结论:高脂饮食诱导的肥胖大鼠味觉感受行为学的变化可能与味蕾甘丙肽及其受体的表达变化存在相互关系。味蕾水平的甘丙肽及其受体GalR2参与营养状态调控大鼠味觉感知及摄食行为的外周机制。
The nutritional and metabolic status alters the peripheral taste perception and food intake by participating in the modulation of taste information integration. The taste receptors and neuropeptides in the taste buds are the important targets of this modulation process. To explore the effects of nutritional status on the expressions of galanin and its receptors in the taste buds, we compared the mRNA levels of galanin and its specific receptor GalR2 in the taste buds among the high-fat diet induced obese rats(HF), chronically restricted diet rats(CR) and control rats. The high-fat diet, half of chow diet, and normal chow diet were given to HF, CR and control groups for 6 weeks, respectively. The body weight and some metabolic indexes, including blood glucose, triglyceride and cholesterol levels were detected. The mRNA expressions of galanin and its receptors in taste buds were determined using real-time PCR. Results showed that compared with control rats, the body weights, levels of blood glucose and triglyceride were significantly elevated in HF rats; while the mRNA expressions of galanin and GalR2 were dramatically decreased. However, galanin mRNA expression in CR rats was increased to 2.3 times of that in control group. Considering the results obtained from our previous studies, we conclude that the behavioral changes in tasting choice of HF rats may be related to the expressions of galanin and GalR2 in the taste buds. The changes of galanin and GalR2 in taste buds are involved in the peripheral mechanism of nutritional status regulating taste perception and feeding behavior in rats.
The nutritional and metabolic status alters the peripheral taste perception and food intake by participating in the modulation of taste information integration. The taste receptors and neuropeptides in the taste buds are the important targets of this modulation process. To explore the effects of nutritional status on the expressions of galanin and its receptors in the taste buds, we compared the mRNA levels of galanin and its specific receptor GalR2 in the taste buds among the high-fat diet induced obese rats(HF), chronically restricted diet rats(CR) and control rats. The high-fat diet, half of chow diet, and normal chow diet were given to HF, CR and control groups for 6 weeks, respectively. The body weight and some metabolic indexes, including blood glucose, triglyceride and cholesterol levels were detected. The mRNA expressions of galanin and its receptors in taste buds were determined using real-time PCR. Results showed that compared with control rats, the body weights, levels of blood glucose and triglyceride were significantly elevated in HF rats; while the mRNA expressions of galanin and GalR2 were dramatically decreased. However, galanin mRNA expression in CR rats was increased to 2.3 times of that in control group. Considering the results obtained from our previous studies, we conclude that the behavioral changes in tasting choice of HF rats may be related to the expressions of galanin and GalR2 in the taste buds. The changes of galanin and GalR2 in taste buds are involved in the peripheral mechanism of nutritional status regulating taste perception and feeding behavior in rats.
引文
1 Katz DB,Nicolelis MA,Simon SA.Nutrient tasting and signaling mechanisms in the gut.IV.There is more to taste than meets the tongue.Am J Physiol Gastrointest Liver Physiol2000;278:G6-G9.
2 Breslin PA,Huang L.Human taste:peripheral anatomy,taste transduction,and coding.Adv Otorhinolaryngol 2006;63:152-190.
3 Shin YK,Martin B,Golden E,Dotson CD,Maudsley S,Kim W,Jang HJ,Mattson MP,Drucker DJ,Egan JM,Munger SD.Modulation of taste sensitivity by GLP-1 signaling.JNeurochem 2008;106:455-463.
4 Herness S,Zhao FL,Kaya N,Shen T,Lu SG,Cao Y.Communication routes within the taste bud by neurotransmitters and neuropeptides.Chem Senses 2005;30 Suppl 1:i37-i38.
5 Tatemoto K,Rokaeus A,Jornvall H,McDonald TJ,Mutt V.Galanin-a novel biologically active peptide from porcine intestine.FEBS Lett 1983;164:124-128.
6 Branchek TA,Smith KE,Gerald C,Walker MW.Galanin receptor subtypes.Trends Pharmacol Sci 2000;21:109-117.
7 Waters SM,Krause JE.Distribution of galanin-1,-2 and-3receptor messenger RNAs in central and peripheral rat tissues.Neuroscience 2000;95:265-271.
8 Koegler FH,Ritter S.Galanin injection into the nucleus of the solitary tract stimulates feeding in rats with lesions of the paraventricular nucleus of the hypothalamus.Physiol Behav1998;63:521-527.
9 Mitchell V,Bouret S,Prevot V,Jennes L,Beauvillain JC.Evidence for expression of galanin receptor Gal-R1 mRNAin certain gonadotropin releasing hormone neurones of the rostral preoptic area.J Neuroendocrinol 1999;11:805-812.
10 Langel U.Galanin receptor ligands.Springerplus 2015;4(Suppl 1):L18.
11 Seta Y,Kataoka S,Toyono T,Toyoshima K.Expression of galanin and the galanin receptor in rat taste buds.Arch Histol Cytol 2006;69:273-280.
12 Seta Y,Toyoshima K.Three-dimensional structure of the gustatory cell in the mouse fungiform taste buds:a computer-assisted reconstruction from serial ultrathin sections.Anat Embryol(Berl)1995;191:83-88.
13 Karatayev O,Baylan J,Leibowitz SF.Increased intake of ethanol and dietary fat in galanin overexpressing mice.Alcohol 2009;43:571-580.
14 Adams AC,Clapham JC,Wynick D,Speakman JR.Feeding behaviour in galanin knockout mice supports a role of galanin in fat intake and preference.J Neuroendocrinol 2008;20:199-206.
15 Suzuki T,Sato T,Kano M,Ichikawa H.The distribution of galanin-immunoreactive nerve fibers in the rat pharynx.Neuropeptides 2013;47:231-236.
16 Fang PH,Yu M,Shi MY,Zhang ZW,Sui YM,Guo LL,Bo P.Galanin peptide family as a modulating target for contribution to metabolic syndrome.Gen Comp Endocrinol 2012;179:115-120.
17 Fang PH,Yu M,Shi MY,He B,Zhang ZW,Bo P.The neuropeptide galanin benefits insulin sensitivity in subjects with type 2 diabetes.Curr Protein Pept Sci 2013;14:669-673.
18 Abot A,Lucas A,Bautzova T,Bessac A,Fournel A,Le-Gonidec S,Valet P,Moro C,Cani PD,Knauf C.Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons.Mol Metab 2018;10:100-108.
19 Spangeus A,El-Salhy M.Myenteric plexus of obese diabetic mice(an animal model of human type 2 diabetes).Histol Histopathol 2001;16:159-165.
20 Zafar MI,Hu CN,Liu DF,Shafqat RA,Gao F.Insulin detemir causes lesser weight gain in comparison to insulin glargine:role on hypothalamic NPY and galanin.J Diabetes Res 2014;2014:458104.doi:10.1155/2014/458104.
21 Abdul-Rahman O,Sasvari-Szekely M,Ver A,Rosta K,Szasz BK,Kereszturi E,Keszler G.Altered gene expression profiles in the hippocampus and prefrontal cortex of type 2diabetic rats.BMC Genomics 2012;13:81.
22 Huang T,Staehler F.Effects of dietary Na+deprivation on epithelial Na+channel(ENaC),BDNF,and trkB mRNAexpression in the rat tongue.BMC Neurosci 2009;10:19.
23 Inoue M,Tordoff MG.Calcium deficiency alters chorda tympani nerve responses to oral calcium chloride.Physiol Behav 1998;63:297-303.
24 Jacobs KM,Mark GP,Scott TR.Taste responses in the nucleus tractus solitarius of sodium-deprived rats.J Physiol1988;406:393-410.
25 McCaughey SA,Scott TR.Rapid induction of sodium appetite modifies taste-evoked activity in the rat nucleus of the solitary tract.Am J Physiol Regul Integr Comp Physiol2000;279:R1121-R1131.
26 Shimura T,Komori M,Yamamoto T.Acute sodium deficiency reduces gustatory responsiveness to NaCl in the parabrachial nucleus of rats.Neurosci Lett 1997;236:33-36.
27 Huang T,Yan J.Dietary sodium deprivation reduces gustatory neural responses of the parabrachial nucleus in rats.Neurosci Lett 2008;432:170-173.
28 Chen K,Yan J,Suo Y,Li J,Wang Q,Lv B.Nutritional status alters saccharin intake and sweet receptor mRNA expression in rat taste buds.Brain Res 2010;1325:53-62.
29 Acar S,Paketci A,Kume T,Demir K,Gursoy Calan O,Bober E,Abaci A.Positive correlation of galanin with insulin resistance and triglyceride levels in obese children.Turk J Med Sci 2018;48:560-568.
30 Legakis I,Mantzouridis T,Mountokalakis T.Positive correlation of galanin with glucose in type 2 diabetes.Diabetes Care 2005;28:759-760.
31 Legakis IN,Mantzouridis T,Mountokalakis T.Positive correlation of galanin with glucose in healthy volunteers during an oral glucose tolerance test.Horm Metab Res 2007;39:53-55.
32 Fang PH,Shi MY,Zhu Y,Bo P,Zhang ZW.Type 2 diabetes mellitus as a disorder of galanin resistance.Exp Gerontol2016;73:72-77.
33 Fang P,Zhang L,Yu M,Sheng Z,Shi M,Zhu Y,Zhang Z,Bo P.Activiated galanin receptor 2 attenuates insulin resistance in skeletal muscle of obese mice.Peptides 2018;99:92-98.
34 Bu L,Chang X,Cheng X,Yao Q,Su B,Sheng C,Qu S.Activated central galanin type 1 receptor alleviated insulin resistance in diabetic rat muscle.J Neurosci Res 2016;94:947-955.
35 Fang P,Yu M,Shi M,He B,Zhang Z,Bo P.The neuropeptide galanin benefits insulin sensitivity in subjects with type 2 diabetes.Curr Protein Pept Sci 2013;14:669-673.
2 Breslin PA,Huang L.Human taste:peripheral anatomy,taste transduction,and coding.Adv Otorhinolaryngol 2006;63:152-190.
3 Shin YK,Martin B,Golden E,Dotson CD,Maudsley S,Kim W,Jang HJ,Mattson MP,Drucker DJ,Egan JM,Munger SD.Modulation of taste sensitivity by GLP-1 signaling.JNeurochem 2008;106:455-463.
4 Herness S,Zhao FL,Kaya N,Shen T,Lu SG,Cao Y.Communication routes within the taste bud by neurotransmitters and neuropeptides.Chem Senses 2005;30 Suppl 1:i37-i38.
5 Tatemoto K,Rokaeus A,Jornvall H,McDonald TJ,Mutt V.Galanin-a novel biologically active peptide from porcine intestine.FEBS Lett 1983;164:124-128.
6 Branchek TA,Smith KE,Gerald C,Walker MW.Galanin receptor subtypes.Trends Pharmacol Sci 2000;21:109-117.
7 Waters SM,Krause JE.Distribution of galanin-1,-2 and-3receptor messenger RNAs in central and peripheral rat tissues.Neuroscience 2000;95:265-271.
8 Koegler FH,Ritter S.Galanin injection into the nucleus of the solitary tract stimulates feeding in rats with lesions of the paraventricular nucleus of the hypothalamus.Physiol Behav1998;63:521-527.
9 Mitchell V,Bouret S,Prevot V,Jennes L,Beauvillain JC.Evidence for expression of galanin receptor Gal-R1 mRNAin certain gonadotropin releasing hormone neurones of the rostral preoptic area.J Neuroendocrinol 1999;11:805-812.
10 Langel U.Galanin receptor ligands.Springerplus 2015;4(Suppl 1):L18.
11 Seta Y,Kataoka S,Toyono T,Toyoshima K.Expression of galanin and the galanin receptor in rat taste buds.Arch Histol Cytol 2006;69:273-280.
12 Seta Y,Toyoshima K.Three-dimensional structure of the gustatory cell in the mouse fungiform taste buds:a computer-assisted reconstruction from serial ultrathin sections.Anat Embryol(Berl)1995;191:83-88.
13 Karatayev O,Baylan J,Leibowitz SF.Increased intake of ethanol and dietary fat in galanin overexpressing mice.Alcohol 2009;43:571-580.
14 Adams AC,Clapham JC,Wynick D,Speakman JR.Feeding behaviour in galanin knockout mice supports a role of galanin in fat intake and preference.J Neuroendocrinol 2008;20:199-206.
15 Suzuki T,Sato T,Kano M,Ichikawa H.The distribution of galanin-immunoreactive nerve fibers in the rat pharynx.Neuropeptides 2013;47:231-236.
16 Fang PH,Yu M,Shi MY,Zhang ZW,Sui YM,Guo LL,Bo P.Galanin peptide family as a modulating target for contribution to metabolic syndrome.Gen Comp Endocrinol 2012;179:115-120.
17 Fang PH,Yu M,Shi MY,He B,Zhang ZW,Bo P.The neuropeptide galanin benefits insulin sensitivity in subjects with type 2 diabetes.Curr Protein Pept Sci 2013;14:669-673.
18 Abot A,Lucas A,Bautzova T,Bessac A,Fournel A,Le-Gonidec S,Valet P,Moro C,Cani PD,Knauf C.Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons.Mol Metab 2018;10:100-108.
19 Spangeus A,El-Salhy M.Myenteric plexus of obese diabetic mice(an animal model of human type 2 diabetes).Histol Histopathol 2001;16:159-165.
20 Zafar MI,Hu CN,Liu DF,Shafqat RA,Gao F.Insulin detemir causes lesser weight gain in comparison to insulin glargine:role on hypothalamic NPY and galanin.J Diabetes Res 2014;2014:458104.doi:10.1155/2014/458104.
21 Abdul-Rahman O,Sasvari-Szekely M,Ver A,Rosta K,Szasz BK,Kereszturi E,Keszler G.Altered gene expression profiles in the hippocampus and prefrontal cortex of type 2diabetic rats.BMC Genomics 2012;13:81.
22 Huang T,Staehler F.Effects of dietary Na+deprivation on epithelial Na+channel(ENaC),BDNF,and trkB mRNAexpression in the rat tongue.BMC Neurosci 2009;10:19.
23 Inoue M,Tordoff MG.Calcium deficiency alters chorda tympani nerve responses to oral calcium chloride.Physiol Behav 1998;63:297-303.
24 Jacobs KM,Mark GP,Scott TR.Taste responses in the nucleus tractus solitarius of sodium-deprived rats.J Physiol1988;406:393-410.
25 McCaughey SA,Scott TR.Rapid induction of sodium appetite modifies taste-evoked activity in the rat nucleus of the solitary tract.Am J Physiol Regul Integr Comp Physiol2000;279:R1121-R1131.
26 Shimura T,Komori M,Yamamoto T.Acute sodium deficiency reduces gustatory responsiveness to NaCl in the parabrachial nucleus of rats.Neurosci Lett 1997;236:33-36.
27 Huang T,Yan J.Dietary sodium deprivation reduces gustatory neural responses of the parabrachial nucleus in rats.Neurosci Lett 2008;432:170-173.
28 Chen K,Yan J,Suo Y,Li J,Wang Q,Lv B.Nutritional status alters saccharin intake and sweet receptor mRNA expression in rat taste buds.Brain Res 2010;1325:53-62.
29 Acar S,Paketci A,Kume T,Demir K,Gursoy Calan O,Bober E,Abaci A.Positive correlation of galanin with insulin resistance and triglyceride levels in obese children.Turk J Med Sci 2018;48:560-568.
30 Legakis I,Mantzouridis T,Mountokalakis T.Positive correlation of galanin with glucose in type 2 diabetes.Diabetes Care 2005;28:759-760.
31 Legakis IN,Mantzouridis T,Mountokalakis T.Positive correlation of galanin with glucose in healthy volunteers during an oral glucose tolerance test.Horm Metab Res 2007;39:53-55.
32 Fang PH,Shi MY,Zhu Y,Bo P,Zhang ZW.Type 2 diabetes mellitus as a disorder of galanin resistance.Exp Gerontol2016;73:72-77.
33 Fang P,Zhang L,Yu M,Sheng Z,Shi M,Zhu Y,Zhang Z,Bo P.Activiated galanin receptor 2 attenuates insulin resistance in skeletal muscle of obese mice.Peptides 2018;99:92-98.
34 Bu L,Chang X,Cheng X,Yao Q,Su B,Sheng C,Qu S.Activated central galanin type 1 receptor alleviated insulin resistance in diabetic rat muscle.J Neurosci Res 2016;94:947-955.
35 Fang P,Yu M,Shi M,He B,Zhang Z,Bo P.The neuropeptide galanin benefits insulin sensitivity in subjects with type 2 diabetes.Curr Protein Pept Sci 2013;14:669-673.