Hypothalamic pro-opiomelanocortin gene delivery ameliorates obesity and glucose intolerance in aged rats

Diabetologia

Volumn 48, Issue 11, 2005, Pages 2376-2385

  Li, G ^a   Zhang, Y ^a,b   Wilsey, J T ^a,b   Scarpace, P J ^a,b  

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

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

AAV; Age related obesity; Diabetes; Gene therapy; Pomc

Indexed keywords

MELANOCORTIN RECEPTOR; MESSENGER RNA; NEUROPEPTIDE; NEUROPEPTIDE Y; PROOPIOMELANOCORTIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARCUATE NUCLEUS; ARTICLE; CONTROLLED STUDY; FATTY ACID BLOOD LEVEL; GENE OVEREXPRESSION; GENE TARGETING; GENETIC CODE; GLUCOSE INTOLERANCE; HYPOTHALAMUS; MALE; NONHUMAN; OBESITY; PRIORITY JOURNAL; RAT; THERMOGENESIS; TRIACYLGLYCEROL BLOOD LEVEL; WEIGHT REDUCTION;

ADIPOSE TISSUE, BROWN; AGING; ANIMALS; BODY WEIGHT; CHOLESTEROL; DEPENDOVIRUS; EATING; FATTY ACIDS, NONESTERIFIED; GENE THERAPY; GENETIC VECTORS; GLUCOSE; GLUCOSE INTOLERANCE; GLUCOSE TOLERANCE TEST; HYPOTHALAMUS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; LEPTIN; MALE; NEUROPEPTIDE Y; OBESITY; PEPTIDE HORMONES; PRO-OPIOMELANOCORTIN; RATS; RATS, INBRED F344; RECEPTOR, MELANOCORTIN, TYPE 3; RECEPTOR, MELANOCORTIN, TYPE 4; TRIGLYCERIDES;

EID: 27744596351     PISSN: 0012186X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00125-005-1943-8     Document Type: Article

References (45)

1. Cone RD (1999) The central melanocortin system and energy homeostasis. Trends Endocrinol Metab 10:211-216
2. 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
3. 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
4. Mizuno TM, Mobbs CV (1999) Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting. Endocrinology 140:814-817
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. Mizuno TM, Kleopoulos SP, Bergen HT, Roberts JL, Priest CA, Mobbs CV (1998) Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting and [corrected] in ob/ob and db/db mice, but is stimulated by leptin. Diabetes 47:294-297
8. Kim EM, O'Hare E, Grace MK, Welch CC, Billington CJ, Levine AS (2000) ARC POMC mRNA and PVN alpha-MSH are lower in obese relative to lean Zucker rats. Brain Res 862:11-16
9. Guan XM, Yu H, Van der Ploeg LH (1998) Evidence of altered hypothalamic pro-opiomelanocortin/neuropeptide Y mRNA expression in tubby mice. Brain Res Mol Brain Res 59:273-279
10. Good DJ, Porter FD, Mahon KA, Parlow AF, Westphal H, Kirsch IR (1997) Hypogonadism and obesity in mice with a targeted deletion of the Nhlh2 gene. Nat Genet 15:397-401
11. Bergen HT, Mizuno TM, Taylor J, Mobbs CV (1998) Hyperphagia and weight gain after gold-thioglucose: relation to hypothalamic neuropeptide Y and proopiomelanocortin. Endocrinology 139:4483-4488
12. Mobbs CV, Bray GA, Atkinson RL et al (2001) Neuroendocrine and pharmacological manipulations to assess how caloric restriction increases life span. J Gerontol A Biol Sci Med Sci 56 (Spec No 1):34-44
13. 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
14. 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
15. Gabriely I, Ma XH, Yang XM et al (2002) Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? Diabetes 51:2951-2958
16. 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
17. Li H, Matheny M, Nicolson M, Tumer N, Scarpace PJ (1997) Leptin gene expression increases with age independent of increasing adiposity in rats. Diabetes 46:2035-2039
18. Larkin LM, Reynolds TH, Supiano MA, Kahn BB, Halter JB (2001) Effect of aging and obesity on insulin responsiveness and glut-4 glucose transporter content in skeletal muscle of Fischer 344xBrown Norway rats. J Gerontol A Biol Sci Med Sci 56:B486-B492
19. 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
20. McMinn JE, Wilkinson CW, Havel PJ, Woods SC, Schwartz MW (2000) Effect of intracerebroventricular alpha-MSH on food intake, adiposity, c-Fos induction, and neuropeptide expression. Am J Physiol Regul Integr Comp Physiol 279:R695-R703
21. 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
22. 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
23. Monahan PE, Samulski RJ (2000) AAV vectors: is clinical success on the horizon? Gene Ther 7:24-30
24. Hildinger M, Auricchio A, Gao G, Wang L, Chirmule N, Wilson JM (2001) Hybrid vectors based on adeno-associated virus serotypes 2 and 5 for muscle-directed gene transfer. J Virol 75:6199-6203
25. Zabner J, Seiler M, Walters R et al (2000) Adeno-associated virus type 5 (AAV5) but not AAV2 binds to the apical surfaces of airway epithelia and facilitates gene transfer. J Virol 74:3852-3858
26. 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
27. Daly TM, Ohlemiller KK, Roberts MS, Vogler CA, Sands MS (2001) Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer. Gene Ther 8:1291-1298
28. Loeb JE, Cordier WS, Harris ME, Weitzman MD, Hope TJ (1999) Enhanced expression of transgenes from adeno-associated virus vectors with the woodchuck hepatitis virus post-transcriptional regulatory element: implications for gene therapy. Hum Gene Ther 10:2295-2305
29. Li G, Klein RL, Matheny M, King MA, Meyer EM, Scarpace PJ (2002) Induction of uncoupling protein 1 by central interleukin-6 gene delivery is dependent on sympathetic innervation of brown adipose tissue and underlies one mechanism of body weight reduction in rats. Neuroscience 115:879-889
30. Zolotukhin S, Potter M, Zolotukhin I et al (2002) Production and purification of serotype 1, 2, and 5 recombinant adeno-associated viral vectors. Methods 28:158-167
31. Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates, 3rd edn. Academic Press, San Diego
32. 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
33. Scarpace PJ, Matheny M, Pollock BH, Tumer N (1997) Leptin increases uncoupling protein expression and energy expenditure. Am J Physiol 273:E226-E230
34. Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277-359
35. Gao GP, Alvira MR, Wang L, Calcedo R, Johnston J, Wilson JM (2002) Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci U S A 99:11854-11859
36. Seeley RJ, Burklow ML, Wilmer KA, Matthews CC et al (2005) The effect of the melanocortin agonist, MT-II, on the defended level of body adiposity. Endocrinology (in press)
37. Scarpace PJ, Matheny M, Zhang Y et al (2002) Leptin-induced leptin resistance reveals separate roles for the anorexic and thermogenic responses in weight maintenance. Endocrinology 143:3026-3035
38. 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
39. 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
40. Shinyama H, Masuzaki H, Fang H, Flier JS (2003) Regulation of melanocortin-4 receptor signaling: agonist-mediated desensitization and internalization. Endocrinology 144:1301-1314
41. Pritchard LE, Turnbull AV, White A (2002) Pro-opiomelanocortin processing in the hypothalamus: impact on melanocortin signalling and obesity. J Endocrinol 172:411-421
42. Appleyard SM, Hayward M, Young JI et al (2003) A role for the endogenous opioid beta-endorphin in energy homeostasis. Endocrinology 144:1753-1760
43. Harrold JA, Widdowson PS, Williams G (2003) beta-MSH: a functional ligand that regulated energy homeostasis via hypothalamic MC4-R? Peptides 24:397-405
44. Gupta G, Cases JA, She L et al (2000) Ability of insulin to modulate hepatic glucose production in aging rats is impaired by fat accumulation. Am J Physiol Endocrinol Metab 278:E985-E991
45. 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