Homeostastic and non-homeostatic functions of melanocortin-3 receptors in the control of energy balance and metabolism

Physiology and Behavior

Volumn 104, Issue 4, 2011, Pages 546-554

  Begriche, Karima ^a   Sutton, Gregory M ^b   Butler, Andrew A ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b PENNINGTON BIOMEDICAL RESEARCH CENTER   (United States)

Author keywords

Anticipation; Circadian rhythm; Clock; Food anticipatory activity; Homeostasis; Hypothalamus; Melanocortin; Satiety

Indexed keywords

GLUCOSE; INSULIN; LEPTIN; LEPTIN RECEPTOR; MELANOCORTIN 3 RECEPTOR;

ANTICIPATION; ARTICLE; CALORIC RESTRICTION; CIRCADIAN RHYTHM; CLINICAL PROTOCOL; CLOCK GENE; CLONING; DIETARY INTAKE; DYSLIPIDEMIA; ENERGY BALANCE; FEEDING; FOOD ANTICIPATORY ACTIVITY; FOREBRAIN; GENE; GENE EXPRESSION; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE INTOLERANCE; HOMEOSTASIS; HUMAN; HYPERGLYCEMIA; HYPERINSULINEMIA; KNOCKOUT MOUSE; LIVER; METABOLISM; NERVE CELL; NERVE TRACT; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; SUPRACHIASMATIC NUCLEUS; WAKEFULNESS; WEIGHT REDUCTION;

ANIMALS; ANTICIPATION, PSYCHOLOGICAL; CIRCADIAN CLOCKS; CIRCADIAN RHYTHM; ENERGY METABOLISM; HOMEOSTASIS; HYPOTHALAMUS; MELANOCORTINS; NEURAL PATHWAYS; RECEPTOR, MELANOCORTIN, TYPE 3; SATIETY RESPONSE; SIGNAL TRANSDUCTION;

EID: 79960409704     PISSN: 00319384     EISSN: 1873507X     Source Type: Journal    
DOI: 10.1016/j.physbeh.2011.04.007     Document Type: Article

References (113)

1. Cannon W.B. Organization for physiological homeostasis. Physiol Rev 1929, 9:399-431.
2. Samuel V.T., Petersen K.F., Shulman G.I. Lipid-induced insulin resistance: unravelling the mechanism. Lancet 2010, 375:2267-2277.
3. Lam C.K., Chari M., Lam T.K. CNS regulation of glucose homeostasis. Physiology (Bethesda) 2009, 24:159-170.
4. Myers M.G., Leibel R.L., Seeley R.J., Schwartz M.W. Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol Metab 2010, 21:643-651.
5. Reaven G.M. Why syndrome X? From Harold Himsworth to the insulin resistance syndrome. Cell Metab 2005, 1:9-14.
6. Accili D. Lilly lecture 2003: the struggle for mastery in insulin action: from triumvirate to republic. Diabetes 2004, 53:1633-1642.
7. Olshansky S.J., Passaro D.J., Hershow R.C., Layden J., Carnes B.A., Brody J., et al. A potential decline in life expectancy in the United States in the 21st century. N Engl J Med 2005, 352:1138-1145.
8. Fontaine K.R., Redden D.T., Wang C., Westfall A.O., Allison D.B. Years of life lost due to obesity. JAMA 2003, 289:187-193.
9. Ten S., Maclaren N. Insulin resistance syndrome in children. J Clin Endocrinol Metab 2004, 89:2526-2539.
10. Hill J.O. Understanding and addressing the epidemic of obesity: an energy balance perspective. Endocr Rev 2006, 27:750-761.
11. Arble D.M., Ramsey K.M., Bass J., Turek F.W. Circadian disruption and metabolic disease: findings from animal models. Best Pract Res Clin Endocrinol Metab 2010, 24:785-800.
12. Ramsey K.M., Bass J. Obeying the clock yields benefits for metabolism. Proc Natl Acad Sci USA 2009, 106:4069-4070.
13. Arble D.M., Bass J., Laposky A.D., Vitaterna M.H., Turek F.W. Circadian timing of food intake contributes to weight gain. Obesity (Silver Spring) 2009, 17:2100-2102.
14. Froy O. Metabolism and circadian rhythms-implications for obesity. Endocr Rev 2010, 31:1-24.
15. Bass J., Takahashi J.S. Circadian integration of metabolism and energetics. Science 2010, 330:1349-1354.
16. Stephan F.K. The "other" circadian system: food as a Zeitgeber. J Biol Rhythms 2002, 17:284-292.
17. Woods S.C. The eating paradox: how we tolerate food. Psychol Rev 1991, 98:488-505.
18. Smith G.P., Stephen C. Woods: A precocious scientist. Physiol Behav 2011, 103:4-9.
19. Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., Friedman J.M. Positional cloning of the mouse obese gene and its human homologue. Nature 1994, 372:425-432.
20. Tartaglia L.A., Dembski M., Weng X., Deng N., Culpepper J., Devos R., et al. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995, 83:1263-1271.
21. Cone R.D. Studies on the physiological functions of the melanocortin system. Endocr Rev 2006, 27:736-749.
22. Ahima R.S., Prabakaran D., Mantzoros C., Qu D., Lowell B., Maratos-Flier E., et al. Role of leptin in the neuroendocrine response to fasting. Nature 1996, 382:250-252.
23. Guo K., McMinn J.E., Ludwig T., Yu Y.H., Yang G., Chen L., et al. Disruption of peripheral leptin signaling in mice results in hyperleptinemia without associated metabolic abnormalities. Endocrinology 2007, 148:3987-3997.
24. Dixit V.D., Schaffer E.M., Pyle R.S., Collins G.D., Sakthivel S.K., Palaniappan R., et al. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest 2004, 114:57-66.
25. Dixit V.D., Mielenz M., Taub D.D., Parvizi N. Leptin induces growth hormone secretion from peripheral blood mononuclear cells via a protein kinase C- and nitric oxide-dependent mechanism. Endocrinology 2003, 144:5595-5603.
26. Asilmaz E., Cohen P., Miyazaki M., Dobrzyn P., Ueki K., Fayzikhodjaeva G., et al. Site and mechanism of leptin action in a rodent form of congenital lipodystrophy. J Clin Invest 2004, 113:414-424.
27. Cohen P., Zhao C., Cai X., Montez J.M., Rohani S.C., Feinstein P., et al. Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest 2001, 108:1113-1121.
28. Kowalski T.J., Liu S.M., Leibel R.L., Chua S.C. Transgenic complementation of leptin-receptor deficiency. I. Rescue of the obesity/diabetes phenotype of LEPR-null mice expressing a LEPR-B transgene. Diabetes 2001, 50:425-435.
29. Cheung C.C., Clifton D.K., Steiner R.A. Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 1997, 138:4489-4492.
30. Seeley R.J., Yagaloff K.A., Fisher S.L., Burn P., Thiele T.E., van Dijk G., et al. Melanocortin receptors in leptin effects. Nature 1997, 390:349.
31. Bagnol D., Lu X.Y., Kaelin C.B., Day H.E., Ollmann M., Gantz I., et al. Anatomy of an endogenous antagonist: relationship between Agouti-related protein and proopiomelanocortin in brain. J Neurosci 1999, 19:RC26.
32. Hill J.W., Elias C.F., Fukuda M., Williams K.W., Berglund E.D., Holland W.L., et al. Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility. Cell Metab 2010, 11:286-297.
33. Huo L., Gamber K., Greeley S., Silva J., Huntoon N., Leng X.H., et al. Leptin-dependent control of glucose balance and locomotor activity by POMC neurons. Cell Metab 2009, 9:537-547.
34. Butler A.A., Kozak L.P. A recurring problem with the analysis of energy expenditure in genetic models expressing lean and obese phenotypes. Diabetes 2010, 59:323-329.
35. Kaiyala K.J., Morton G.J., Leroux B.G., Ogimoto K., Wisse B., Schwartz M.W. Identification of body fat mass as a major determinant of metabolic rate in mice. Diabetes 2011, 59:1657-1666.
36. Kozak L.P. Brown fat and the myth of diet-induced thermogenesis. Cell Metab 2010, 11:263-267.
37. Obici S. Molecular targets for obesity therapy in the brain. Endocrinology 2009, 150:2512-2517.
38. Coppari R., Ramadori G., Elmquist J.K. The role of transcriptional regulators in central control of appetite and body weight. Nat Clin Pract Endocrinol Metab 2009, 5:160-166.
39. Shin A.C., Zheng H., Berthoud H.R. An expanded view of energy homeostasis: neural integration of metabolic, cognitive, and emotional drives to eat. Physiol Behav 2009, 97:572-580.
40. Kaiyala K.J., Schwartz M.W. Toward a more complete (and less controversial) understanding of energy expenditure and its role in obesity, pathogenesis. Diabetes 2011, 60:17-23.
41. Cannon B., Nedergaard J. Nonshivering thermogenesis and its adequate measurement in metabolic studies. J Exp Biol 2011, 214:242-253.
42. Obici S., Feng Z., Tan J., Liu L., Karkanias G., Rossetti L. Central melanocortin receptors regulate insulin action. J Clin Invest 2001, 108:1079-1085.
43. Gutierrez-Juarez R., Obici S., Rossetti L. Melanocortin-independent effects of leptin on hepatic glucose fluxes. J Biol Chem 2004, 279:49704-49715.
44. Pocai A., Morgan K., Buettner C., Gutierrez-Juarez R., Obici S., Rossetti L. Central leptin acutely reverses diet-induced hepatic insulin resistance. Diabetes 2005, 54:3182-3189.
45. Zhou L., Sutton G.M., Rochford J.J., Semple R.K., Lam D.D., Oksanen L.J., et al. Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathways. Cell Metab 2007, 6:398-405.
46. Nogueiras R., Wiedmer P., Perez-Tilve D., Veyrat-Durebex C., Keogh J.M., Sutton G.M., et al. The central melanocortin system directly controls peripheral lipid metabolism. J Clin Invest 2007, 117:3475-3488.
47. O'Rahilly S. Human genetics illuminates the paths to metabolic disease. Nature 2009, 462:307-314.
48. Farooqi I.S., O'Rahilly S. Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract Endocrinol Metab 2008, 4:569-577.
49. Cone R.D. Anatomy and regulation of the central melanocortin system. Nat Neurosci 2005, 8:571-578.
50. Garfield A.S., Lam D.D., Marston O.J., Przydzial M.J., Heisler L.K. Role of central melanocortin pathways in energy homeostasis. Trends Endocrinol Metab 2009, 20:203-215.
51. Fan W., Boston B.A., Kesterson R.A., Hruby V.J., Cone R.D. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 1997, 385:165-168.
52. Tung Y.C., Piper S.J., Yeung D., O'Rahilly S., Coll A.P. A comparative study of the central effects of specific proopiomelancortin (POMC)-derived melanocortin peptides on food intake and body weight in pomc null mice. Endocrinology 2006, 147:5940-5947.
53. Lechan R.M., Fekete C. Role of melanocortin signaling in the regulation of the hypothalamic-pituitary-thyroid (HPT) axis. Peptides 2006, 27:310-325.
54. Ollmann M.M., Wilson B.D., Yang Y.K., Kerns J.A., Chen Y., Gantz I., et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 1997, 278:135-138.
55. Shutter J.R., Graham M., Kinsey A.C., Scully S., Luthy R., Stark K.L. Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes Dev 1997, 11:593-602.
56. Nijenhuis W.A., Oosterom J., Adan R.A. AgRP(83-132) acts as an inverse agonist on the human-melanocortin-4 receptor. Mol Endocrinol 2001, 15:164-171.
57. Buch T.R., Heling D., Damm E., Gudermann T., Breit A. Pertussis toxin-sensitive signaling of melanocortin-4 receptors in hypothalamic GT1-7 cells defines agouti-related protein as a biased agonist. J Biol Chem 2009, 284:26411-26420.
58. Williams K.W., Margatho L.O., Lee C.E., Choi M., Lee S., Scott M.M., et al. Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons. J Neurosci 2010, 30:2472-2479.
59. Ibrahim N., Bosch M.A., Smart J.L., Qiu J., Rubinstein M., Ronnekleiv O.K., et al. Hypothalamic proopiomelanocortin neurons are glucose responsive and express K(ATP) channels. Endocrinology 2003, 144:1331-1340.
60. Claret M., Smith M.A., Batterham R.L., Selman C., Choudhury A.I., Fryer L.G., et al. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J Clin Invest 2007, 117:2325-2336.
61. Chen H.Y., Trumbauer M.E., Chen A.S., Weingarth D.T., Adams J.R., Frazier E.G., et al. Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology 2004, 145:2607-2612.
62. Ramadori G., Fujikawa T., Fukuda M., Anderson J., Morgan D.A., Mostoslavsky R., et al. SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity. Cell Metab 2010, 12:78-87.
63. Dietrich M.O., Antunes C., Geliang G., Liu Z.W., Borok E., Nie Y., et al. Agrp neurons mediate Sirt1's action on the melanocortin system and energy balance: roles for Sirt1 in neuronal firing and synaptic plasticity. J Neurosci 2010, 30:11815-11825.
64. Mountjoy K.G., Mortrud M.T., Low M.J., Simerly R.B., Cone R.D. Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol 1994, 8:1298-1308.
65. Kishi T., Aschkenasi C.J., Lee C.E., Mountjoy K.G., Saper C.B., Elmquist J.K. Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. J Comp Neurol 2003, 457:213-235.
66. Liu H., Kishi T., Roseberry A.G., Cai X., Lee C.E., Montez J.M., et al. Transgenic mice expressing green fluorescent protein under the control of the melanocortin-4 receptor promoter. J Neurosci 2003, 23:7143-7154.
67. Chen A.S., Metzger J.M., Trumbauer M.E., Guan X.M., Yu H., Frazier E.G., et al. Role of the melanocortin-4 receptor in metabolic rate and food intake in mice. Transgenic Res 2000, 9:145-154.
68. Ste Marie L., Miura G.I., Marsh D.J., Yagaloff K., Palmiter R.D. A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors. Proc Natl Acad Sci USA 2000, 97:12339-12344.
69. Kumar K.G., Sutton G.M., Dong J.Z., Roubert P., Plas P., Halem H.A., et al. Analysis of the therapeutic functions of novel melanocortin receptor agonists in MC3R- and MC4R-deficient C57BL/6J mice. Peptides 2009, 30:1892-1900.
70. Zhang Y., Kilroy G.E., Henagan T.M., Prpic-Uhing V., Richards W.G., Bannon A.W., et al. Targeted deletion of melanocortin receptor subtypes 3 and 4, but not CART, alters nutrient partitioning and compromises behavioral and metabolic responses to leptin. FASEB J 2005, 19:1482-1491.
71. Fekete C., Marks D.L., Sarkar S., Emerson C.H., Rand W.M., Cone R.D., et al. Effect of Agouti-related protein in regulation of the hypothalamic-pituitary-thyroid axis in the melanocortin 4 receptor knockout mouse. Endocrinology 2004, 145:4816-4821.
72. Rahmouni K., Haynes W.G., Morgan D.A., Mark A.L. Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin. J Neurosci 2003, 23:5998-6004.
73. Huszar D., Lynch C.A., Fairchild-Huntress V., Dunmore J.H., Fang Q., Berkemeier L.R., et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997, 88:131-141.
74. Roselli-Rehfuss L., Mountjoy K.G., Robbins L.S., Mortrud M.T., Low M.J., Tatro J.B., et al. Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc Natl Acad Sci USA 1993, 90:8856-8860.
75. Butler A.A., Kesterson R.A., Khong K., Cullen M.J., Pelleymounter M.A., Dekoning J., et al. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 2000, 141:3518-3521.
76. Chen A.S., Marsh D.J., Trumbauer M.E., Frazier E.G., Guan X.M., Yu H., et al. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet 2000, 26:97-102.
77. Marsh D.J., Hollopeter G., Huszar D., Laufer R., Yagaloff K.A., Fisher S.L., et al. Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Nat Genet 1999, 21:119-122.
78. Butler A.A. The melanocortin system and energy balance. Peptides 2006, 27:281-290.
79. Sutton G.M., Trevaskis J.L., Hulver M.W., McMillan R.P., Markward N.J., Babin M.J., et al. Diet-genotype interactions in the development of the obese, insulin-resistant phenotype of C57BL/6J mice lacking melanocortin-3 or -4 receptors. Endocrinology 2006, 147:2183-2196.
80. Ellacott K.L., Murphy J.G., Marks D.L., Cone R.D. Obesity-induced inflammation in white adipose tissue is attenuated by loss of melanocortin-3 receptor signaling. Endocrinology 2007, 148:6186-6194.
81. Sutton G.M., Perez-Tilve D., Nogueiras R., Fang J., Kim J.K., Cone R.D., et al. The melanocortin-3 receptor is required for entrainment to meal intake. J Neurosci 2008, 28:12946-12955.
82. Begriche K., Sutton G.M., Fang J., Butler A.A. The role of melanocortin neuronal pathways in circadian biology: a new homeostatic output involving melanocortin-3 receptors?. Obes Rev 2009, 10(SUPPL. 2):14-24.
83. Sutton G.M., Begriche K., Kumar K.G., Gimble J.M., Perez-Tilve D., Nogueiras R., et al. Central nervous system melanocortin-3 receptors are required for synchronizing metabolism during entrainment to restricted feeding during the light cycle. FASEB J 2010, 24:862-872.
84. Choi S., Wong L.S., Yamat C., Dallman M.F. Hypothalamic ventromedial nuclei amplify circadian rhythms: do they contain a food-entrained endogenous oscillator?. J Neurosci 1998, 18:3843-3852.
85. Gooley J.J., Schomer A., Saper C.B. The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms. Nat Neurosci 2006, 9:398-407.
86. Mieda M., Williams S.C., Richardson J.A., Tanaka K., Yanagisawa M. The dorsomedial hypothalamic nucleus as a putative food-entrainable circadian pacemaker. Proc Natl Acad Sci USA 2006, 103:12150-12155.
87. Moriya T., Aida R., Kudo T., Akiyama M., Doi M., Hayasaka N., et al. The dorsomedial hypothalamic nucleus is not necessary for food-anticipatory circadian rhythms of behavior, temperature or clock gene expression in mice. Eur J Neurosci 2009, 29:1447-1460.
88. Davidson A.J. Lesion studies targeting food-anticipatory activity. Eur J Neurosci 2009, 30:1658-1664.
89. Green C.B., Takahashi J.S., Bass J. The meter of metabolism. Cell 2008, 134:728-742.
90. Dibner C., Schibler U., Albrecht U. The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol 2010, 72:517-549.
91. Burris T.P. Nuclear hormone receptors for heme: REV-ERBalpha and REV-ERBbeta are ligand-regulated components of the mammalian clock. Mol Endocrinol 2008, 22:1509-1520.
92. Yin L., Wu N., Lazar M.A. Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian rhythm and metabolism. Nucl Recept Signal 2010, 8:e001.
93. O'Neill J.S., Reddy A.B. Circadian clocks in human red blood cells. Nature 2010, 469:498-503.
94. Storch K.F., Weitz C.J. Daily rhythms of food-anticipatory behavioral activity do not require the known circadian clock. Proc Natl Acad Sci USA 2009, 106:6808-6813.
95. Feillet C.A., Ripperger J.A., Magnone M.C., Dulloo A., Albrecht U., Challet E. Lack of food anticipation in Per2 mutant mice. Curr Biol 2006, 16:2016-2022.
96. Wahlsten D., Metten P., Phillips T.J., Boehm S.L., Burkhart-Kasch S., Dorow J., et al. Different data from different labs: lessons from studies of gene-environment interaction. J Neurobiol 2003, 54:283-311.
97. Crabbe J.C., Wahlsten D., Dudek B.C. Genetics of mouse behavior: interactions with laboratory environment. Science 1999, 284:1670-1672.
98. Takahashi J.S., Hong H.K., Ko C.H., McDearmon E.L. The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev Genet 2008, 9:764-775.
99. Takahashi J.S., Shimomura K., Kumar V. Searching for genes underlying behavior: lessons from circadian rhythms. Science 2008, 322:909-912.
100. Sahar S., Sassone-Corsi P. Metabolism and cancer: the circadian clock connection. Nat Rev Cancer 2009, 9:886-896.
101. Mieda M., Williams S.C., Sinton C.M., Richardson J.A., Sakurai T., Yanagisawa M. Orexin neurons function in an efferent pathway of a food-entrainable circadian oscillator in eliciting food-anticipatory activity and wakefulness. J Neurosci 2004, 24:10493-10501.
102. LeSauter J., Hoque N., Weintraub M., Pfaff D.W., Silver R. Stomach ghrelin-secreting cells as food-entrainable circadian clocks. Proc Natl Acad Sci USA 2009, 106:13582-13587.
103. Blum I.D., Patterson Z., Khazall R., Lamont E.W., Sleeman M.W., Horvath T.L., et al. Reduced anticipatory locomotor responses to scheduled meals in ghrelin receptor deficient mice. Neuroscience 2009, 164:351-359.
104. Damiola F., Le Minh N., Preitner N., Kornmann B., Fleury-Olela F., Schibler U. Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev 2000, 14:2950-2961.
105. Mistlberger R.E. Food-anticipatory circadian rhythms: concepts and methods. Eur J Neurosci 2009, 30:1718-1729.
106. Buhr E.D., Yoo S.H., Takahashi J.S. Temperature as a universal resetting cue for mammalian circadian oscillators. Science 2010, 330:379-385.
107. Bruss M.D., Khambatta C.F., Ruby M.A., Aggarwal I., Hellerstein M.K. Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates. Am J Physiol Endocrinol Metab 2010, 298:E108-E116.
108. Trevaskis J.L., Gawronska-Kozak B., Sutton G.M., McNeil M., Stephens J.M., Smith S.R., et al. Role of adiponectin and inflammation in insulin resistance of Mc3r and Mc4r knockout mice. Obesity (Silver Spring) 2007, 15:2664-2672.
109. Getting S.J. Targeting melanocortin receptors as potential novel therapeutics. Pharmacol Ther 2006, 111:1-15.
110. Gantz I., Konda Y., Tashiro T., Shimoto Y., Miwa H., Munzert G., et al. Molecular cloning of a novel melanocortin receptor. J Biol Chem 1993, 268:8246-8250.
111. Le Martelot G., Claudel T., Gatfield D., Schaad O., Kornmann B., Sasso G.L., et al. REV-ERBalpha participates in circadian SREBP signaling and bile acid homeostasis. PLoS Biol 2009, 7:e1000181.
112. Lamia K.A., Storch K.F., Weitz C.J. Physiological significance of a peripheral tissue circadian clock. Proc Natl Acad Sci USA 2008, 105:15172-15177.
113. Stanley S., Pinto S., Segal J., Perez C.A., Viale A., DeFalco J., et al. Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically. Proc Natl Acad Sci USA 2010, 107:7024-7029.