Lean rats with hypothalamic pro-opiomelanocortin overexpression exhibit greater diet-induced obesity and impaired central melanocortin responsiveness

Diabetologia

Volumn 50, Issue 7, 2007, Pages 1490-1499

  Li, G ^a   Zhang, Y ^a,b   Cheng, K Y ^a   Scarpace, P J ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Diet induced obesity; Gene transfer; Hypothalamus; Melanocortin; Pro opiomelanocortin

Indexed keywords

AGOUTI RELATED PROTEIN; ALPHA INTERMEDIN; ANTIOBESITY AGENT; APPETITE STIMULANT; LEPTIN; MELANOCORTIN; MELANOCORTIN 3 RECEPTOR; MELANOCORTIN 4 RECEPTOR; MELANOCORTIN AGONIST; MELANOCORTIN ANTAGONIST; MELANOCORTIN RECEPTOR; MELANOTAN; MESSENGER RNA; N ACETYL ALPHA INTERMEDIN[4-10]CYCLO[4 NORLEUCINE 5 ASPARTIC ACID 7 [3 (2 NAPHTHYL)ALANINE] 10 LYSINAMIDE]; NEUROPEPTIDE; PARVOVIRUS VECTOR; PROOPIOMELANOCORTIN; UNCLASSIFIED DRUG; UNCOUPLING PROTEIN 1;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARCUATE NUCLEUS; ARTICLE; BODY WEIGHT; BRAIN; BROWN ADIPOSE TISSUE; BROWN NORWAY RAT; CONTROLLED STUDY; ENERGY BALANCE; FOOD INTAKE; GENE DELIVERY SYSTEM; GENE OVEREXPRESSION; HOMEOSTASIS; HORMONE BLOOD LEVEL; HYPOTHALAMUS; INTRAABDOMINAL FAT; LIPID DIET; MALE; NONHUMAN; OBESITY; PRIORITY JOURNAL; RAT; RAT STRAIN; SPRAGUE DAWLEY RAT; VIRUS RECOMBINANT;

ADIPOSE TISSUE; ANIMAL FEED; ANIMALS; BODY WEIGHT; HYPOTHALAMUS; MALE; MELANOCORTINS; OBESITY; PRO-OPIOMELANOCORTIN; RATS; RATS, INBRED F344; RECOMBINANT PROTEINS; RNA, MESSENGER;

EID: 34249932831     PISSN: 0012186X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00125-007-0685-1     Document Type: Article

References (43)

1. Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD (1997) Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 385:165-168
2. Huszar D, Lynch CA, Fairchild-Huntress V et al (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88:131-141
3. Mizuno TM, Mobbs CV (1999) Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting. Endocrinology 140:814-817
4. Cone RD (1999) The central melanocortin system and energy homeostasis. Trends Endocrinol Metab 10:211-216
5. Butler AA, Kesterson RA, Khong K et al (2000) A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 141:3518-3521
6. Obici S, Feng Z, Tan J, Liu L, Karkanias G, Rossetti L (2001) Central melanocortin receptors regulate insulin action. J Clin Invest 108:1079-1085
7. Cone RD (2005) Anatomy and regulation of the central melanocortin system. Nat Neurosci 8:571-578
8. Yaswen L, Diehl N, Brennan MB, Hochgeschwender U (1999) Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med 5:1066-1070
9. Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 19:155-157
10. Chen AS, Marsh DJ, Trumbauer ME et al (2000) Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet 26:97-102
11. Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB, Flier JS (1995) Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat Med 1:1311-1314
12. El Haschimi K, Pierroz DD, Hileman SM, Bjorbaek C, Flier JS (2000) Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest 105:1827-1832
13. Burguera B, Couce ME, Curran GL et al (2000) Obesity is associated with a decreased leptin transport across the blood-brain barrier in rats. Diabetes 49:1219-1223
14. Schwartz MW, Seeley RJ, Campfield LA, Burn P, Baskin DG (1996) Identification of targets of leptin action in rat hypothalamus. J Clin Invest 98:1101-1106
15. Schwartz MW, Seeley RJ, Woods SC et al (1997) Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes 46:2119-2123
16. Cheung CC, Clifton DK, Steiner RA (1997) Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 138:4489-4492
17. Baskin DG, Hahn TM, Schwartz MW (1999) Leptin sensitive neurons in the hypothalamus. Horm Metab Res 31:345-350c
18. Elias CF, Kelly JF, Lee CE et al (2000) Chemical characterization of leptin-activated neurons in the rat brain. J Comp Neurol 423:261-281
19. Scarpace PJ, Matheny M, Zhang Y et al (2002) Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats. Neuropharmacology 42:548-561
20. Wilsey J, Zolotukhin S, Prima V, Scarpace PJ (2003) Central leptin gene therapy fails to overcome leptin resistance associated with diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 285:R1011-R1020
21. Hansen MJ, Ball MJ, Morris MJ (2001) Enhanced inhibitory feeding response to alpha-melanocyte stimulating hormone in the diet-induced obese rat. Brain Res 892:130-137
22. Pierroz DD, Ziotopoulou M, Ungsunan L, Moschos S, Flier JS, Mantzoros CS (2002) Effects of acute and chronic administration of the melanocortin agonist MTII in mice with diet-induced obesity. Diabetes 51:1337-1345
23. Zhang Y, Matheny M, Tumer N, Scarpace PJ (2004) Aged-obese rats exhibit robust responses to a melanocortin agonist and antagonist despite leptin resistance. Neurobiol Aging 25:1349-1360
24. Li G, Zhang Y, Wilsey JT, Scarpace PJ (2004) Unabated anorexic and enhanced thermogenic responses to melanotan II in diet-induced obese rats despite reduced melanocortin 3 and 4 receptor expression. J Endocrinol 182:123-132
25. Bluher S, Ziotopoulou M, Bullen JW Jr et al (2004) Responsiveness to peripherally administered melanocortins in lean and obese mice. Diabetes 53:82-90
26. Li G, Mobbs CV, Scarpace PJ (2003) Central pro-opiomelanocortin gene delivery results in hypophagia, reduced visceral adiposity, and improved insulin sensitivity in genetically obese Zucker rats. Diabetes 52:1951-1957
27. Li G, Zhang Y, Wilsey JT, Scarpace PJ (2005) Hypothalamic pro-opiomelanocortin gene delivery ameliorates obesity and glucose intolerance in aged rats. Diabetologia 48:2376-2385
28. Uhler M, Herbert E (1983) Complete amino acid sequence of mouse pro-opiomelanocortin derived from the nucleotide sequence of pro-opiomelanocortin cDNA. J Biol Chem 258:257-261
29. Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277-359
30. Schwartz MW, Woods SC, Seeley RJ, Barsh GS, Baskin DG, Leibel RL (2003) Is the energy homeostasis system inherently biased toward weight gain? Diabetes 52:232-238
31. Mizuno TM, Kelley KA, Pasinetti GM, Roberts JL, Mobbs CV (2003) Transgenic neuronal expression of proopiomelanocortin attenuates hyperphagic response to fasting and reverses metabolic impairments in leptin-deficient obese mice. Diabetes 52:2675-2683
32. Savontaus E, Breen TL, Kim A, Yang LM, Chua SC Jr, Wardlaw SL (2004) Metabolic effects of transgenic melanocyte-stimulating hormone overexpression in lean and obese mice. Endocrinology 145:3881-3891
33. Shinyama H, Masuzaki H, Fang H, Flier JS (2003) Regulation of melanocortin-4 receptor signaling: agonist-mediated desensitization and internalization. Endocrinology 144:1301-1314
34. de Pedro N, Delgado MJ, Alonso-Bedate M (1995) Central administration of beta-endorphin increases food intake in goldfish: pretreatment with the opioid antagonist naloxone. Regul Pept 55:189-195
35. Low MJ, Hayward MD, Appleyard SM, Rubinstein M (2003) State-dependent modulation of feeding behavior by proopiomelanocortin-derived beta-endorphin. Ann N Y Acad Sci 994:192-201
36. Haynes WG, Morgan DA, Djalali A, Sivitz WI, Mark AL (1999) Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic. Hypertension 33:542-547
37. Cettour-Rose P, Rohner-Jeanrenaud F (2002) The leptin-like effects of 3-d peripheral administration of a melanocortin agonist are more marked in genetically obese Zucker (fa/fa) than in lean rats. Endocrinology 143:2277-2283
38. Williams DL, Bowers RR, Bartness TJ, Kaplan JM, Grill HJ (2003) Brainstem melanocortin 3/4 receptor stimulation increases uncoupling protein gene expression in brown fat. Endocrinology 144:4692-4697
39. Scarpace PJ, Matheny M, Tumer N, Cheng KY, Zhang Y (2005) Leptin resistance exacerbates diet-induced obesity and is associated with diminished maximal leptin signalling capacity in rats. Diabetologia 48:1075-1083
40. Zhang J, Matheny MK, Tumer N, Mitchell MK, Scarpace PJ (2007) Leptin antagonist reveals that the normalization of caloric intake and the thermic effect of food following high-fat feeding are leptin dependent. Am J Physiol Regul Integr Comp Physiol 292:R868-R874
41. Horvath TL (2005) The hardship of obesity: a soft-wired hypothalamus. Nat Neurosci 8:561-565
42. Horvath TL, Naftolin F, Kalra SP, Leranth C (1992) Neuropeptide-Y innervation of beta-endorphin-containing cells in the rat mediobasal hypothalamus: a light and electron microscopic double immunostaining analysis. Endocrinology 131:2461-2467
43. Cowley MA, Smart JL, Rubinstein M et al (2001) Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411:480-484