Temporal changes in nutritional state affect hypothalamic POMC peptide levels independently of leptin in adult male mice

American Journal of Physiology - Endocrinology and Metabolism

Volumn 306, Issue 8, 2014, Pages

  Mercer, Aaron J ^a   Stuart, Ronald C ^b   Attard, Courtney A ^a   Otero Corchon, Veronica ^a   Nillni, Eduardo A ^b,c   Low, Malcolm J ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b BROWN UNIVERSITY   (United States)

^c RHODE ISLAND HOSPITAL   (United States)

Author keywords

Arcuate nucleus; Energy homeostasis; Hypothalamus; Leptin; Metabolism; Neural networks; Obesity; Proopiomelanocortin; Proopiomelanocortin neurons

Indexed keywords

ALPHA INTERMEDIN; BETA ENDORPHIN; CORTICOTROPIN; HYPOTHALAMUS EXTRACT; LEPTIN; PROOPIOMELANOCORTIN; RED FLUORESCENT PROTEIN;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CALORIC INTAKE; CONTROLLED STUDY; DIET RESTRICTION; ENERGY BALANCE; FOOD INTAKE; HORMONAL THERAPY; HORMONE BLOOD LEVEL; HYPOTHALAMUS; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; LIPID DIET; MALE; MEASUREMENT; MOUSE; NONHUMAN; NUTRITIONAL STATUS; OSMOTIC MINIPUMP; PEPTIDE SYNTHESIS; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; RADIOIMMUNOASSAY; SUPPLEMENTATION; YOUNG ADULT;

ARCUATE NUCLEUS; ENERGY HOMEOSTASIS; HYPOTHALAMUS; LEPTIN; METABOLISM; NEURAL NETWORKS; OBESITY; PROOPIOMELANOCORTIN; PROOPIOMELANOCORTIN NEURONS;

ANIMALS; BODY WEIGHT; DIET; EATING; HYPOTHALAMUS; LEPTIN; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; NUTRITIONAL STATUS; PRO-OPIOMELANOCORTIN; TIME FACTORS;

EID: 84900560471     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00540.2013     Document Type: Article

References (70)

1. Balthasar N, Coppari R, McMinn J, Liu SM, Lee CE, Tang V, Kenny CD, McGovern RA, Chua SC Jr, Elmquist JK, Lowell BB. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42: 983-991, 2004.
2. Barsh GS, Schwartz MW. Genetic approaches to studying energy balance: perception and integration. Nat Rev Genet 3: 589-600, 2002.
3. Benani A, Hryhorczuk C, Gouaze A, Fioramonti X, Brenachot X, Guissard C, Krezymon A, Duparc T, Colom A, Nedelec E, Rigault C, Lemoine A, Gascuel J, Gerardy-Schahn R, Valet P, Knauf C, Lorsignol A, Penicaud L. Food intake adaptation to dietary fat involves PSA-dependent rewiring of the arcuate melanocortin system in mice. J Neurosci 32: 11970-11979, 2012.
4. Berglund ED, Vianna CR, Donato J Jr, Kim MH, Chuang JC, Lee CE, Lauzon DA, Lin P, Brule LJ, Scott MM, Coppari R, Elmquist JK. Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J Clin Invest 122: 1000-1009, 2012.
5. Betley JN, Cao ZF, Ritola KD, Sternson SM. Parallel, redundant circuit organization for homeostatic control of feeding behavior. Cell 155: 1337-1350, 2013.
6. Bhatnagar S, Dallman MF. The paraventricular nucleus of the thalamus alters rhythms in core temperature and energy balance in a state-dependent manner. Brain Res 851: 66-75, 1999.
7. Bowen H, Mitchell TD, Harris RB. Method of leptin dosing, strain, and group housing influence leptin sensitivity in high-fat-fed weanling mice. Am J Physiol Regul Integr Comp Physiol 284: R87-R100, 2003.
8. Cakir I, Cyr NE, Perello M, Litvinov BP, Romero A, Stuart RC, Nillni EA. Obesity induces hypothalamic endoplasmic reticulum stress and impairs proopiomelanocortin (POMC) post-translational processing. J Biol Chem 288: 17675-17688, 2013.
9. Champy MF, Selloum M, Zeitler V, Caradec C, Jung B, Rousseau S, Pouilly L, Sorg T, Auwerx J. Genetic background determines metabolic phenotypes in the mouse. Mamm Genome 19: 318-331, 2008.
10. Cowley MA, Smart JL, Rubinstein M, Cerdan MG, Diano S, Horvath TL, Cone RD, Low MJ. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411: 480-484, 2001.
11. De Souza CT, Araujo EP, Bordin S, Ashimine R, Zollner RL, Boschero AC, Saad MJ, Velloso LA. Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146: 4192-4199, 2005.
12. Diaz EO, Prentice AM, Goldberg GR, Murgatroyd PR, Coward WA. Metabolic response to experimental overfeeding in lean and overweight healthy-volunteers. Am J Clin Nutr 56: 641-655, 1992.
13. Dutia R, Meece K, Dighe S, Kim AJ, Wardlaw SL. beta-Endorphin antagonizes the effects of alpha-MSH on food intake and body weight. Endocrinology 153: 4246-4255, 2012.
14. Eerola K, Nordlund W, Virtanen S, Dickens AM, Mattila M, Ruohonen ST, Chua SC Jr, Wardlaw SL, Savontaus M, Savontaus E. Lentivirus mediated alpha-melanocyte stimulating hormone overexpression in the hypothalamus decreases diet induced obesity in mice. J Neuroendocrinol doi:10.1111/jne.12109.
15. Elias CF, Aschkenasi C, Lee C, Kelly J, Ahima RS, Bjorbaek C, Flier JS, Saper CB, Elmquist JK. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 23: 775-786, 1999.
16. Elias CF, Saper CB, Maratos-Flier E, Tritos NA, Lee C, Kelly J, Tatro JB, Hoffman GE, Ollmann MM, Barsh GS, Sakurai T, Yanagisawa M, Elmquist JK. Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J Comp Neurol 402: 442-459, 1998.
17. Enriori PJ, Evans AE, Sinnayah P, Jobst EE, Tonelli-Lemos L, Billes SK, Glavas MM, Grayson BE, Perello M, Nillni EA, Grove KL, Cowley MA. Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. Cell Metab 5: 181-194, 2007.
18. Ernst MB, Wunderlich CM, Hess S, Paehler M, Mesaros A, Koralov SB, Kleinridders A, Husch A, Munzberg H, Hampel B, Alber J, Kloppenburg P, Bruning JC, Wunderlich FT. Enhanced Stat3 activation in POMC neurons provokes negative feedback inhibition of leptin and insulin signaling in obesity. J Neurosci 29: 11582-11593, 2009.
19. Fan CN, Liu XL, Shen WW, Deckelbaum RJ, Qi KM. The regulation of leptin, leptin receptor and pro-opiomelanocortin expression by N-3 PUFAs in diet-induced obese mice is not related to the methylation of their promoters. Nutr Metab 8: 31, 2011.
20. Farooqi IS, O'Rahilly S. Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract Endocrinol Metab 4: 569-577, 2008.
21. Franklin KB, Paxinos G. The Mouse Brain in Sterotaxic Coordinates, Compact (3rd Ed.). Philadelphia, PA: Elsevier, 2008, p. 256.
22. Gamber KM, Huo L, Ha S, Hairston JE, Greeley S, Bjorbaek C. Over-expression of leptin receptors in hypothalamic POMC neurons increases susceptibility to diet-induced obesity. PLoS One 7: e30485, 2012.
23. Gambert SR, Garthwaite TL, Pontzer CH, Hagen TC. Fasting associated with decrease in hypothalamic beta-endorphin. Science 210: 1271-1272, 1980.
24. Gout J, Sarafian D, Tirard J, Blondet A, Vigier M, Rajas F, Mithieux G, Begeot M, Naville D. Leptin infusion and obesity in mouse cause alterations in the hypothalamic melanocortin system. Obesity (Silver Spring) 16: 1763-1769, 2008.
25. Guo L, Munzberg H, Stuart RC, Nillni EA, Bjorbaek C. N-acetylation of hypothalamic alpha-melanocyte-stimulating hormone and regulation by leptin. Proc Natl Acad Sci USA 101: 11797-11802, 2004.
26. Hansen MJ, Schioth HB, Morris MJ. Feeding responses to a melanocortin agonist and antagonist in obesity induced by a palatable high-fat diet. Brain Res 1039: 137-145, 2005.
27. Hentges ST, Otero-Corchon V, Pennock RL, King CM, Low MJ. Proopiomelanocortin expression in both GABA and glutamate neurons. J Neurosci 29: 13684-13690, 2009.
28. Horvath TL, Sarman B, Garcia-Caceres C, Enriori PJ, Sotonyi P, Shanabrough M, Borok E, Argente J, Chowen JA, Perez-Tilve D, Pfluger PT, Bronneke HS, Levin BE, Diano S, Cowley MA, Tschop MH. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proc Natl Acad Sci USA 107: 14875-14880, 2010.
29. 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 dietinduced obesity. Brain Res 992: 9-19, 2003.
30. Kelley AE, Baldo BA, Pratt WE. A proposed hypothalamic-thalamicstriatal axis for the integration of energy balance, arousal, and food reward. J Comp Neurol 493: 72-85, 2005.
31. Kim EM, Welch CC, Grace MK, Billington CJ, Levine AS. Chronic food restriction and acute food deprivation decrease mRNA levels of opioid peptides in arcuate nucleus. Am J Physiol Regul Integr Comp Physiol 270: R1019-R1024, 1996.
32. King CM, Hentges ST. Relative number and distribution of murine hypothalamic proopiomelanocortin neurons innervating distinct target sites. PLoS One 6: e25864, 2011.
33. Koch CE, Lowe C, Pretz D, Steger J, Williams LM, Tups A. High fat diet induces leptin resistance. J Neuroendocrinol 26: 58-67, 2014.
34. Korner J, Chua SC Jr, Williams JA, Leibel RL, Wardlaw SL. Regulation of hypothalamic proopiomelanocortin by leptin in lean and obese rats. Neuroendocrinology 70: 377-383, 1999.
35. Lee M, Kim A, Chua SC Jr, Obici S, Wardlaw SL. Transgenic MSH overexpression attenuates the metabolic effects of a high-fat diet. Am J Physiol Endocrinol Metab 293: E121-E131, 2007.
36. Lin S, Storlien LH, Huang XF. Leptin receptor, NPY, POMC mRNA expression in the diet-induced obese mouse brain. Brain Res 875: 89-95, 2000.
37. Liu T, Kong D, Shah BP, Ye C, Koda S, Saunders A, Ding JB, Yang Z, Sabatini BL, Lowell BB. Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron 73: 511-522, 2012.
38. Marchant NJ, Furlong TM, McNally GP. Medial dorsal hypothalamus mediates the inhibition of reward seeking after extinction. J Neurosci 30: 14102-14115, 2010.
39. Marco A, Kisliouk T, Weller A, Meiri N. High fat diet induces hypermethylation of the hypothalamic Pomc promoter and obesity in postweaning rats. Psychoneuroendocrinology 38: 2844-2853, 2013.
40. McMinn JE, Wilkinson CW, Havel PJ, Woods SC, Schwartz MW. Effect of intracerebroventricular α-MSH on food intake, adiposity, c-Fos induction, and neuropeptide expression. Am J Physiol Regul Integr Comp Physiol 279: R695-R703, 2000.
41. Mercer AJ, Hentges ST, Meshul CK, Low MJ. Unraveling the central proopiomelanocortin neural circuits. Front Neurosci 7: 19, 2013.
42. Moraes JC, Coope A, Morari J, Cintra DE, Roman EA, Pauli JR, Romanatto T, Carvalheira JB, Oliveira AL, Saad MJ, Velloso LA. High-fat diet induces apoptosis of hypothalamic neurons. PLoS One 4: e5045, 2009.
43. Mori H, Hanada R, Hanada T, Aki D, Mashima R, Nishinakamura H, Torisu T, Chien KR, Yasukawa H, Yoshimura A. Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med 10: 739-743, 2004.
44. Mountjoy KG. Functions for pro-opiomelanocortin-derived peptides in obesity and diabetes. Biochem J 428: 305-324, 2010.
45. Newton AJ, Hess S, Paeger L, Vogt MC, Fleming Lascano J, Nillni EA, Bruning JC, Kloppenburg P, Xu AW. AgRP innervation onto POMC neurons increases with age and is accelerated with chronic high-fat feeding in male mice. Endocrinology 154: 172-183, 2013.
46. Nillni EA. Regulation of prohormone convertases in hypothalamic neurons: implications for prothyrotropin-releasing hormone and proopiomelanocortin. Endocrinology 148: 4191-4200, 2007.
47. Ozcan L, Ergin AS, Lu A, Chung J, Sarkar S, Nie D, Myers MG Jr, Ozcan U. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab 9: 35-51, 2009.
48. Perello M, Cakir I, Cyr NE, Romero A, Stuart RC, Chiappini F, Hollenberg AN, Nillni EA. Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level. Am J Physiol Endocrinol Metab 299: E976-E989, 2010.
49. Perello M, Stuart R, Nillni EA. Prothyrotropin-releasing hormone targets its processing products to different vesicles of the secretory pathway. J Biol Chem 283: 19936-19947, 2008.
50. Perello M, Stuart RC, Nillni EA. Differential effects of fasting and leptin on proopiomelanocortin peptides in the arcuate nucleus and in the nucleus of the solitary tract. Am J Physiol Endocrinol Metab 292: E1348-E1357, 2007.
51. Petervari E, Szabad AO, Soos S, Garami A, Szekely M, Balasko M. Central alpha-MSH infusion in rats: disparate anorexic vs. metabolic changes with aging. Regul Pept 166: 105-111, 2011.
52. Pinto S, Roseberry AG, Liu H, Diano S, Shanabrough M, Cai X, Friedman JM, Horvath TL. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 304: 110-115, 2004.
53. Pritchard LE, White A. Neuropeptide processing and its impact on melanocortin pathways. Endocrinology 148: 4201-4207, 2007.
54. Shi H, Sorrell JE, Clegg DJ, Woods SC, Seeley RJ. The roles of leptin receptors on POMC neurons in the regulation of sex-specific energy homeostasis. Physiol Behav 100: 165-172, 2010.
55. Solomon G, Atkins A, Shahar R, Gertler A, Monsonego-Ornan E. Effect of peripherally administered leptin antagonist on whole-body metabolism, and bone microarchitecture and biomechanical properties in mouse. Am J Physiol Endocrinol Metab 306: E14-E27, 2014.
56. Soos S, Balasko M, Jech-Mihalffy A, Szekely M, Petervari Anorexic vs E. metabolic effects of central leptin infusion in rats of various ages and nutritional states. J Mol Neurosci 41: 97-104, 2010.
57. Soos S, Petervari E, Szekely M, Jech-Mihalffy A, Balasko M. Complex catabolic effects of central alpha-MSH infusion in rats of altered nutritional states: differences from leptin. J Mol Neurosci 43: 209-216, 2011.
58. Surwit RS, Edwards CL, Murthy S, Petro AE. Transient effects of long-term leptin supplementation in the prevention of diet-induced obesity in mice. Diabetes 49: 1203-1208, 2000.
59. Tam J, Fukumura D, Jain RK. A mathematical model of murine metabolic regulation by leptin: energy ealance and defense of a stable body weight. Cell Metab 9: 52-63, 2009.
60. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschop MH, Schwartz MW. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 122: 153-162, 2012.
61. Tschop MH, Speakman JR, Arch JR, Auwerx J, Bruning JC, Chan L, Eckel RH, Farese RV Jr, Galgani JE, Hambly C, Herman MA, Horvath TL, Kahn BB, Kozma SC, Maratos-Flier E, Muller TD, Munzberg H, Pfluger PT, Plum L, Reitman ML, Rahmouni K, Shulman GI, Thomas G, Kahn CR, Ravussin E. A guide to analysis of mouse energy metabolism. Nat Methods 9: 57-63, 2012.
62. Tsujii S, Nakai Y, Fukata J, Nakaishi S, Takahashi H, Usui T, Imura H. Effects of food deprivation and high fat diet on immunoreactive beta-endorphin levels in brain regions of Zucker rats. Endocrinol Jpn 34: 903-909, 1987.
63. van den Heuvel JK, van Rozen AJ, Adan RA, la Fleur SE. An overview on how components of the melanocortin system respond to different high energy diets. Eur J Pharmacol 660: 207-212, 2011.
64. Villanueva EC, Myers MG Jr. Leptin receptor signaling and the regulation of mammalian physiology. Int J Obes (Lond) 32, Suppl 7: S8-S12, 2008.
65. Vong L, Ye C, Yang Z, Choi B, Chua S Jr, Lowell BB. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71: 142-154, 2011.
66. Wardlaw SL. Hypothalamic proopiomelanocortin processing and the regulation of energy balance. Eur J Pharmacol 660: 213-219, 2011.
67. Warne JP, Xu AW. Metabolic transceivers: in tune with the central melanocortin system. Trends Endocrinol Metab 24: 68-75, 2013.
68. Williams KW, Elmquist JK. From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior. Nat Neurosci 15: 1350-1355, 2012.
69. Zeltser LM, Seeley RJ, Tschop MH. Synaptic plasticity in neuronal circuits regulating energy balance. Nat Neurosci 15: 1336-1342, 2012.
70. Ziotopoulou M, Mantzoros CS, Hileman SM, Flier JS. Differential expression of hypothalamic neuropeptides in the early phase of dietinduced obesity in mice. Am J Physiol Endocrinol Metab 279: E838-E845, 2000.