Kisspeptin/Kiss1R在机体能量代谢调节中的作用及其机制的研究进展
|
摘要
吻素/吻素受体(Kisspeptin/Kiss1R)系统由Kiss1基因编码的神经肽Kisspeptin及其受体Kiss1R组成。近年的研究表明,机体不同能量代谢状态可影响Kisspeptin的表达。在能量负平衡状态时,下丘脑Kiss1 mRNA表达水平下降,脂肪组织Kiss1 mRNA表达增加。而在高脂饮食或肥胖状态下,下丘脑、脂肪组织中Kiss1 mRNA的表达水平可表现为增加、降低或不变。此外,Kiss1R基因敲除可导致成年雌性小鼠出现肥胖表型及糖代谢异常,而外源注射Kisspeptin对啮齿类动物的摄食有一定的抑制作用。因此,学者们认为Kisspeptin/Kiss1R系统也参与了机体能量代谢的调节。
Kisspeptin / Kiss1 R system consists of the neuropeptide Kisspeptin( encoded by Kiss1) and its receptor Kiss1 R. It has been demonstrated that changes in energy status can affect Kisspeptin levels. Energy deficiency reduces hypothalamic Kisspeptin expression and increases Kiss1 mRNA in adipose tissue. But under the circumstance of obesity or high fat diet,Kisspeptin expression is quite different,showing increase,decrease or no change. Kiss1 R knockout results in impaired glucose intolerance and obesity in adult female mice,while kisspeptin administration may reduce food intake in rodents. Therefore,it has been reported that Kisspeptin / Kiss1 R system is involved in the energy metabolism regulation.
Kisspeptin / Kiss1 R system consists of the neuropeptide Kisspeptin( encoded by Kiss1) and its receptor Kiss1 R. It has been demonstrated that changes in energy status can affect Kisspeptin levels. Energy deficiency reduces hypothalamic Kisspeptin expression and increases Kiss1 mRNA in adipose tissue. But under the circumstance of obesity or high fat diet,Kisspeptin expression is quite different,showing increase,decrease or no change. Kiss1 R knockout results in impaired glucose intolerance and obesity in adult female mice,while kisspeptin administration may reduce food intake in rodents. Therefore,it has been reported that Kisspeptin / Kiss1 R system is involved in the energy metabolism regulation.
引文
[1]Topaloglu AK,Tello JA,Kotan LD,et al.Inactivating KISS1 mutation and hypogonadotropic hypogonadism[J].N Engl J Med,2012,366(7):629-635.
[2]Castellano JM,Tena-Sempere M.Metabolic regulation of kisspeptin[J].Adv Exp Med Biol,2013,784:363-383.
[3]Lee JH,Miele ME,Hicks DJ,et al.Ki SS-1,a novel human malignant melanoma metastasis-suppressor gene[J].J Natl Cancer Inst,1996,88(23):1731-1737.
[4]de Roux N,Genin E,Carel JC,et al.Hypogonadotropic hypogonadism due to loss of function of the Ki SS1-derived peptide receptor GPR54[J].Proc Natl Acad Sci U S A,2003,100(19):10972-10976.
[5]Harms JF,Welch DR,Miele ME.KISS1 metastasis suppression and emergent pathways[J].Clin Exp Metastasis,2003,20(1):11-18.
[6]Muir AI,Chamberlain L,Elshourbagy NA,et al.AXOR12,a novel human G protein-coupled receptor,activated by the peptide Ki SS-1[J].J Biol Chem,2001,276(31):28969-28975.
[7]Castellano JM,Navarro VM,Fernández-Fernández R,et al.Changes in hypothalamic Ki SS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition[J].Endocrinology,2005,146(9):3917-3925.
[8]Brown RE,Imran SA,Ur E,et al.Ki SS-1 mRNA in adipose tissue is regulated by sex hormones and food intake[J].Mol Cell Endocrinol,2008,281(1/2):64-72.
[9]Matsuzaki T,Iwasa T,Kinouchi R,et al.Fasting reduces the kiss1mRNA levels in the caudal hypothalamus of gonadally intact adult female rats[J].Endocr J,2011,58(11):1003-1012.
[10]Luque RM,Kineman RD,Tena-Sempere M.Regulation of hypothalamic expression of Ki SS-1 and GPR54 genes by metabolic factors:analyses using mouse models and a cell line[J].Endocrinology,2007,148(10):4601-4611.
[11]Roa J,Garcia-Galiano D,Varela L,et al.The mammalian target of rapamycin as novel central regulator of puberty onset via modulation of hypothalamic Kiss1 system[J].Endocrinology,2009,150(11):5016-5026.
[12]Kalamatianos T,Grimshaw SE,Poorun R,et al.Fasting reduces Ki SS-1 expression in the anteroventral periventricular nucleus(AVPV):effects of fasting on the expression of Ki SS-1 and neuropeptide Y in the AVPV or arcuate nucleus of female rats[J].J Neuroendocrinol,2008,20(9):1089-1097.
[13]Backholer K,Smith JT,Rao A,et al.Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells[J].Endocrinology,2010,151(5):2233-2243.
[14]Castellano JM,Navarro VM,Roa J,et al.Alterations in hypothalamic Ki SS-1 system in experimental diabetes:early changes and functional consequences[J].Endocrinology,2009,150(2):784-794.
[15]Castellano JM,Navarro VM,Fernández-Fernández R,et al.Expression of hypothalamic Ki SS-1 system and rescue of defective gonadotropic responses by kisspeptin in streptozotocin-induced diabetic male rats[J].Diabetes,2006,55(9):2602-2610.
[16]Xu J,Kirigiti MA,Grove KL,et al.Regulation of food intake and gonadotropin-releasing hormone/luteinizing hormone during lactation:role of insulin and leptin[J].Endocrinology,2009,150(9):4231-4240.
[17]Yamada S,Uenoyama Y,Kinoshita M,et al.Inhibition of metastin(kisspeptin-54)-GPR54 signaling in the arcuate nucleus-median eminence region during lactation in rats[J].Endocrinology,2007,148(5):2226-2232.
[18]Castellano JM,Bentsen AH,Sánchez-Garrido MA,et al.Early metabolic programming of puberty onset:impact of changes in postnatal feeding and rearing conditions on the timing of puberty and development of the hypothalamic kisspeptin system[J].Endocrinology,2011,152(9):3396-3408.
[19]Quennell JH,Howell CS,Roa J,et al.Leptin deficiency and dietinduced obesity reduce hypothalamic kisspeptin expression in mice[J].Endocrinology,2011,152(4):1541-1550.
[20]Cockwell H,Wilkinson DA,Bouzayen R,et al.KISS1 expression in human female adipose tissue[J].Arch Gynecol Obstet,2013,287(1):143-147.
[21]Tolson KP,Garcia C,Yen S,et al.Impaired kisspeptin signaling decreases metabolism and promotes glucose intolerance and obesity[J].J Clin Invest,2014,124(7):3075-3079.
[22]Fu LY,van den Pol AN.Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism[J].J Neurosci,2010,30(30):10205-10219.
[23]Stengel A,Wang L,Goebel-Stengel M,et al.Centrally injected kisspeptin reduces food intake by increasing meal intervals in mice[J].Neuroreport,2011,22(5):253-257.
[24]Wahab F,Bano R,Jabeen S,et al.Effect of peripheral kisspeptin administration on adiponectin,leptin,and resistin secretion under fed and fasting conditions in the adult male rhesus monkey(Macaca mulatta)[J].Horm Metab Res,2010,42(8):570-574.
[25]Smith JT,Acohido BV,Clifton DK,et al.Ki SS-1 neurones are direct targets for leptin in the ob/ob mouse[J].J Neuroendocrinol,2006,18(4):298-303.
[26]Qiu J,Fang Y,Bosch MA,et al.Guinea pig kisspeptin neurons are depolarized by leptin via activation of TRPC channels[J].Endocrinology,2011,152(4):1503-1514.
[27]Morelli A,Marini M,Mancina R,et al.Sex steroids and leptin regulate the"first Kiss"(Ki SS 1/G-protein-coupled receptor 54 system)in human gonadotropin-releasing-hormone-secreting neuroblasts[J].J Sex Med,2008,5(5):1097-1113.
[2]Castellano JM,Tena-Sempere M.Metabolic regulation of kisspeptin[J].Adv Exp Med Biol,2013,784:363-383.
[3]Lee JH,Miele ME,Hicks DJ,et al.Ki SS-1,a novel human malignant melanoma metastasis-suppressor gene[J].J Natl Cancer Inst,1996,88(23):1731-1737.
[4]de Roux N,Genin E,Carel JC,et al.Hypogonadotropic hypogonadism due to loss of function of the Ki SS1-derived peptide receptor GPR54[J].Proc Natl Acad Sci U S A,2003,100(19):10972-10976.
[5]Harms JF,Welch DR,Miele ME.KISS1 metastasis suppression and emergent pathways[J].Clin Exp Metastasis,2003,20(1):11-18.
[6]Muir AI,Chamberlain L,Elshourbagy NA,et al.AXOR12,a novel human G protein-coupled receptor,activated by the peptide Ki SS-1[J].J Biol Chem,2001,276(31):28969-28975.
[7]Castellano JM,Navarro VM,Fernández-Fernández R,et al.Changes in hypothalamic Ki SS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition[J].Endocrinology,2005,146(9):3917-3925.
[8]Brown RE,Imran SA,Ur E,et al.Ki SS-1 mRNA in adipose tissue is regulated by sex hormones and food intake[J].Mol Cell Endocrinol,2008,281(1/2):64-72.
[9]Matsuzaki T,Iwasa T,Kinouchi R,et al.Fasting reduces the kiss1mRNA levels in the caudal hypothalamus of gonadally intact adult female rats[J].Endocr J,2011,58(11):1003-1012.
[10]Luque RM,Kineman RD,Tena-Sempere M.Regulation of hypothalamic expression of Ki SS-1 and GPR54 genes by metabolic factors:analyses using mouse models and a cell line[J].Endocrinology,2007,148(10):4601-4611.
[11]Roa J,Garcia-Galiano D,Varela L,et al.The mammalian target of rapamycin as novel central regulator of puberty onset via modulation of hypothalamic Kiss1 system[J].Endocrinology,2009,150(11):5016-5026.
[12]Kalamatianos T,Grimshaw SE,Poorun R,et al.Fasting reduces Ki SS-1 expression in the anteroventral periventricular nucleus(AVPV):effects of fasting on the expression of Ki SS-1 and neuropeptide Y in the AVPV or arcuate nucleus of female rats[J].J Neuroendocrinol,2008,20(9):1089-1097.
[13]Backholer K,Smith JT,Rao A,et al.Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells[J].Endocrinology,2010,151(5):2233-2243.
[14]Castellano JM,Navarro VM,Roa J,et al.Alterations in hypothalamic Ki SS-1 system in experimental diabetes:early changes and functional consequences[J].Endocrinology,2009,150(2):784-794.
[15]Castellano JM,Navarro VM,Fernández-Fernández R,et al.Expression of hypothalamic Ki SS-1 system and rescue of defective gonadotropic responses by kisspeptin in streptozotocin-induced diabetic male rats[J].Diabetes,2006,55(9):2602-2610.
[16]Xu J,Kirigiti MA,Grove KL,et al.Regulation of food intake and gonadotropin-releasing hormone/luteinizing hormone during lactation:role of insulin and leptin[J].Endocrinology,2009,150(9):4231-4240.
[17]Yamada S,Uenoyama Y,Kinoshita M,et al.Inhibition of metastin(kisspeptin-54)-GPR54 signaling in the arcuate nucleus-median eminence region during lactation in rats[J].Endocrinology,2007,148(5):2226-2232.
[18]Castellano JM,Bentsen AH,Sánchez-Garrido MA,et al.Early metabolic programming of puberty onset:impact of changes in postnatal feeding and rearing conditions on the timing of puberty and development of the hypothalamic kisspeptin system[J].Endocrinology,2011,152(9):3396-3408.
[19]Quennell JH,Howell CS,Roa J,et al.Leptin deficiency and dietinduced obesity reduce hypothalamic kisspeptin expression in mice[J].Endocrinology,2011,152(4):1541-1550.
[20]Cockwell H,Wilkinson DA,Bouzayen R,et al.KISS1 expression in human female adipose tissue[J].Arch Gynecol Obstet,2013,287(1):143-147.
[21]Tolson KP,Garcia C,Yen S,et al.Impaired kisspeptin signaling decreases metabolism and promotes glucose intolerance and obesity[J].J Clin Invest,2014,124(7):3075-3079.
[22]Fu LY,van den Pol AN.Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism[J].J Neurosci,2010,30(30):10205-10219.
[23]Stengel A,Wang L,Goebel-Stengel M,et al.Centrally injected kisspeptin reduces food intake by increasing meal intervals in mice[J].Neuroreport,2011,22(5):253-257.
[24]Wahab F,Bano R,Jabeen S,et al.Effect of peripheral kisspeptin administration on adiponectin,leptin,and resistin secretion under fed and fasting conditions in the adult male rhesus monkey(Macaca mulatta)[J].Horm Metab Res,2010,42(8):570-574.
[25]Smith JT,Acohido BV,Clifton DK,et al.Ki SS-1 neurones are direct targets for leptin in the ob/ob mouse[J].J Neuroendocrinol,2006,18(4):298-303.
[26]Qiu J,Fang Y,Bosch MA,et al.Guinea pig kisspeptin neurons are depolarized by leptin via activation of TRPC channels[J].Endocrinology,2011,152(4):1503-1514.
[27]Morelli A,Marini M,Mancina R,et al.Sex steroids and leptin regulate the"first Kiss"(Ki SS 1/G-protein-coupled receptor 54 system)in human gonadotropin-releasing-hormone-secreting neuroblasts[J].J Sex Med,2008,5(5):1097-1113.