Control of metabolic and cardiovascular function by the leptin-brain melanocortin pathway

IUBMB Life

Volumn 65, Issue 8, 2013, Pages 692-698

  Do Carmo, Jussara M ^a   Da Silva, Alexandre A ^a   Dubinion, John ^a   Sessums, Price O ^a   Ebaady, Sabira H ^a   Wang, Zhen ^a   Hall, John E ^a  

^a UNIVERSITY OF MISSISSIPPI SCHOOL OF MEDICINE   (United States)

Author keywords

blood pressure; glucose regulation; hypertension; obesity; sympathetic activity

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; CORTICOTROPIN RELEASING FACTOR; GHRELIN; GLUCOSE; INSULIN; INSULIN RECEPTOR SUBSTRATE 2; JANUS KINASE 2; LEPTIN; MELANOCORTIN; MELANOCORTIN 4 RECEPTOR; OXYTOCIN; PEPTIDE YY; PHOSPHATIDYLINOSITOL 3 KINASE; STAT3 PROTEIN; STEROID HORMONE; SUPPRESSOR OF CYTOKINE SIGNALING;

ADRENERGIC RECEPTOR BLOCKING; ADRENERGIC SYSTEM; ARCUATE NUCLEUS; BLOOD BRAIN BARRIER; BODY FAT DISTRIBUTION; CARDIOVASCULAR FUNCTION; CENTRAL NERVOUS SYSTEM; ELEVATED BLOOD PRESSURE; ENERGY BALANCE; ENERGY EXPENDITURE; GENE MUTATION; GLUCOSE HOMEOSTASIS; GLUCOSE UTILIZATION; HUMAN; HYPERGLYCEMIA; HYPERINSULINEMIA; HYPERLEPTINEMIA; HYPERTENSION; IMMUNOREACTIVITY; INSULIN RESISTANCE; INTRACELLULAR SIGNALING; KIDNEY DENERVATION; KIDNEY TUBULE ABSORPTION; LIPID DIET; METABOLIC SYNDROME X; METABOLISM; MORBID OBESITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; ORTHOSTATIC HYPOTENSION; PHENOTYPE; PRESSORECEPTOR REFLEX; PROTEIN DEPHOSPHORYLATION; PROTEIN PHOSPHORYLATION; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SLEEP DISORDERED BREATHING; SODIUM RETENTION; SYMPATHETIC TONE; WEIGHT GAIN; WHITE ADIPOSE TISSUE; ZONA INCERTA;

EID: 84890773381     PISSN: 15216543     EISSN: 15216551     Source Type: Journal    
DOI: 10.1002/iub.1187     Document Type: Review

References (67)

1. Yach, D., Stuckler, D., and, Brownell, K. D., (2006) Epidemiologic and economic consequences of the global epidemics of obesity and diabetes. Nat Med. 12, 62-66. (Pubitemid 43050076)
2. Department of Health and Human Services-Center for disease Control and Prevention. (2011) Obesity and overweight trends in the U.S. Available at: http://www.cdc.gov/nccdphp/dnpa/obesity/trend/index.htm.
3. Anderson, S. E., and, Whitaker, R. C., (2009) Prevalence of obesity among US preschool children in different racial and ethnic groups. Arch. Pediatr. Adolesc. Med. 163, 344-348.
4. Wilson, P. W. F., D'Agostino, R. B., Sullivan, L., Parise, H., and, Kannel, W. B., (2002) Overweight and obesity as determinants of cardiovascular risk-the Framingham experience. Arch. Intern. Med. 162, 1867-1872.
5. Hall, J. E., Crook, E. D., Jones, D. W., Wofford, M. R., et al. (2002) Mechanisms of obesity-associated cardiovascular and renal disease. Am. J. Med. Sci. 324, 127-137.
6. Davy, K. P., and, Hall, J. E., (2004) Obesity and hypertension: two epidemics or one? Am. J. Physiol. Regul. Integr. Comp. Physiol. 286, R803-R813. (Pubitemid 38506821)
7. Hall, J. E., (2003) The kidney, hypertension, and obesity. Hypertension 41, 625-633. (Pubitemid 36314565)
8. Hypponen, E., Virtanen, S. M., Kenward, M. G., Knip, M., Akerblom, H. K., et al. (2000) Obesity, increased linear growth, and risk of type 1 diabetes in children. Diab. Care 23, 1755-1760.
9. Vaz, M., Jennings, G., Turner, A., Cox, H., Lambert, G., et al. (1997) Regional sympathetic nervous activity and oxygen consumption in obese normotensive subjects. Circulation 18, 3423-3429. (Pubitemid 27513415)
10. Davy, K. P., and, Orr, J. S., (2009) Sympathetic nervous system behavior in human obesity. Neurosci. Biobehav. Rev. 33, 116-124.
11. Hall, J. E., da Silva, A. A., do Carmo, J. M., Dubinion, J., Hamza, S., et al. (2010) Obesity-induced hypertension: role of sympathetic nervous system, leptin, and melanocortins. J. Biol. Chem. 285, 17271-17276.
12. Wofford, M. R., Anderson, D. C., Brown, C. A., Jones, D. W., Miller, M. E., et al. (2001) Antihypertensive effect of alpha and beta adrenergic blockade in obese and lean hypertensive subjects. Am. J. Hypertens. 14, 694-698. (Pubitemid 32612535)
13. Kassab, S., Kato, T., Wilkins, F. C., Chen, R., Hall, J. E., et al. (1995) Renal denervation attenuates the sodium retention and hypertension associated with obesity. Hypertension 25, 893-897.
14. Straznicky, N. E., Eikelis, N., Lambert, E. A., and, Esler, M. D., (2008) Mediators of sympathetic activation in metabolic syndrome obesity. Curr. Hypertens. Rep. 10, 440-447.
15. Mancia, G., Bousquet, P., Elghozi, J. L., Esler, M., Grassi, G., et al. (2007) The sympathetic nervous system and the metabolic syndrome. J. Hypertens. 25, 909-920. (Pubitemid 46573105)
16. da Silva, A. A., do Carmo, J. M., Dubinion, J., and, Hall, J. E., (2009) The role of the sympathetic nervous system in obesity-related hypertension. Curr. Hypertens. Rep. 11, 206-11.
17. Schwartz, M. W., Woods, S. C., Porte, D., Jr., Seeley, R. J., and, Baskin, D. G., (2000) Central nervous system control of food intake. Nature 404, 661-671. (Pubitemid 30205071)
18. Farooqi, S., and, O'Rahilly, S., (2006) Genetics of obesity in humans. Endocr. Rev. 27, 710-718. (Pubitemid 44936054)
19. Ozata, M., Ozdemir, I. C., and, Licinio, J., (1999) Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J. Clin. Endocrinol. Metab. 10, 3686-3695. (Pubitemid 30645226)
20. Mark, A. L., Shafer, R. A., Correia, M. L., Morgan, D. A., Sigmund, C. D., et al. (1999) Contrasting blood pressure effects of obesity in leptin deficient ob/ob mice and agouti yellow obese mice. J. Hypertens. 17, 1949-1953. (Pubitemid 30345336)
21. Cohen, P., Connie, Z., Cai, X., Montez, J. M., Rohani, S. C., et al. (2001) Selective deletion of leptin receptor in neurons leads to obesity. J. Clin. Invest. 108, 1113-1121. (Pubitemid 32995369)
22. do Carmo, J. M., Bassi, M., da Silva, A. A., and, Hall, J. E., (2008) Control of cardiovascular, metabolic and respiratory functions during prolonged obesity in leptin-deficient and diet-induced obese mice. Hypertension 15, 109.
23. Kalil, G. Z., and, Haynes, W. G., (2012) Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications. Hypertens. Res. 35, 4-16.
24. Correia, M. L., Haynes, W. G., Rahmouni, K., Morgan, D. A., Sivitz, W. I., et al. (2002) The concept of selective leptin resistance: evidence from agouti yellow obese mice. Diabetes 51, 439-442. (Pubitemid 34764800)
25. Rahmouni, K., Fath, M. A., Seo, S., Thedens, D. R., Berry, C. J., et al. (2008) Leptin resistance contributes to obesity and hypertension in mouse models of Bardet-Biedl syndrome. J. Clin. Invest. 118, 1458-1467. (Pubitemid 351500439)
26. Rahmouni, K., Morgan, D. A., Morgan, G. M., Mark, A. L., and, Haynes, W. G., (2005) Role of selective leptin resistance in diet-induced obesity hypertension. Diabetes 54, 2012-2018. (Pubitemid 40911263)
27. Shek, E. W., Brands, M. W., and, Hall, J. E., (1998) Chronic leptin infusion increases arterial pressure. Hypertension 31, 409-414.
28. Carlyle, M., Jones, O. B., Kuo, J. J., and, Hall, J. E., (2002) Chronic cardiovascular and renal actions of leptin-role of adrenergic activity. Hypertension 39, 496-501. (Pubitemid 34165172)
29. Aizawa-Abe, M., Ogawa, Y., Masuzaki, H., Ebihara, K., Satoh, N., et al. (2000) Pathophysiological role of leptin in obesity-related hypertension. J. Biol. Chem. 105, 1243-1252. (Pubitemid 30266077)
30. Prior, L. J., Eikelis, N., Armitage, J. A., Davern, P. J., Burke, S. L., et al. (2010) Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits. Hypertension 55, 862-868.
31. Mark, A. L., Correia, M. L., Rahmouni, K., and, Haynes, W. G., (2002) Selective leptin resistance: a new concept in leptin physiology with cardiovascular implications. J. Hypertens. 20, 1245-1250. (Pubitemid 34925659)
32. Ghilardi, N., and, Skoda, R. C., (1997) The leptin receptor activates Janus kinase 2 and signals for proliferation in a factor-dependent cell line. Mol. Endocrinol. 11, 393-399. (Pubitemid 27147006)
33. Gao, Q., Wolfgang, M. J., and, Neschen, S., (2004) Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. Proc. Natl. Acad. Sci. USA. 101, 4661-4666. (Pubitemid 38437467)
34. Dubinion, J. H., do Carmo, J. M., Adi, A., Hamza, S., da Silva, A. A., et al. (2013) Role of proopiomelanocortin neuron Stat3 in regulating arterial pressure and mediating the chronic effects of leptin. Hypertension 61, 1066-1074.
35. Rahmouni, K., Haynes, W. G., Morgan, D. A., and, Mark, A. L., (2002) Intracellular mechanisms involved in leptin regulation of sympathetic outflow. Hypertension 41, 763-767.
36. Choudhury, A. I., Heffron, H., Smith, M. A., Al-Qassab, H., Xu, A. W., et al. (2005) The role of insulin receptor substrate 2 in hypothalamic and beta cell function. J. Clin. Invest. 15, 940-950. (Pubitemid 40489398)
37. Lin, X., Taguchi, A., Park, S., Kushner, J. A., Li, F., et al. (2004) Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes. J. Clin. Invest. 114, 908-916. (Pubitemid 39578718)
38. Burks, D., de Mora, J. F., Schubert, M., Withers, D.J., Myers, M. G., et al. (2000) IRS-2 pathways integrate female reproduction and energy homeostasis. Nature 407, 377-382.
39. Krajewska, M., Banares, S., Zhang, E. E., Huang, X., Scadeng, M., et al. Development of diabesity in mice with neuronal deletion of Shp2 tyrosine phosphatase. Am. J. Pathol. 172, 1312-1324.
40. Zhang, E. E., Chapeau, E., Hagihara, K., and, Feng, G. S., (2004) Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism. Proc. Natl. Acad. Sci. USA. 9, 16064-16069. (Pubitemid 39507927)
41. Kloek, C., Haq, A. K., Dunn, S. L., Lavery, H. J., Banks, A. S., et al. (2002) Regulation of Jak kinases by intracellular leptin receptor sequences. J. Biol. Chem. 277, 41547-41555. (Pubitemid 35257458)
42. Vong, L., Ye, C., Yang, Z., Choi, B., Chua, S. Jr., et al. (2011) Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71, 142-154.
43. Harlan, S. M., Morgan, D. A., Agassandian, K., Guo, D. F., Cassell, M. D., et al. (2011) Ablation of the leptin receptor in the hypothalamic arcuate nucleus abrogates leptin-induced sympathetic activation. Circ. Res. 108, 808-812.
44. do Carmo, J. M., da Silva, A. A., Cai, Z., Lin, S., Dubinion, J. H., et al. (2011) Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons. Hypertension 57, 918-926.
45. Myers, M. P., Anderson, J. N., Cheng, A., Tremblay, M. L., Horvath, C. M., et al. (2001) TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B. J. Biol. Chem. 276, 47771-47774.
46. Belin de Chantemele, E. J., Muta, K., Mintz, J., Tremblay, M. L., Marrero, M. B., et al. (2009). Protein tyrosine phosphatase 1B, a major regulator of leptin-mediated control of cardiovascular function. Circulation 120, 753-763.
47. Bjorbaek, C., El-Haschimi, K., Frantz, J. D., and, Flier, J. S., (1999) The role of SOCS3 in leptin signaling and leptin resistance. J. Biol. Chem. 274, 30059-30065.
48. Mori, H., Hanada, R., Hanada, T., Aki, D., Mashima, R., et al. (2004) Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat. Med. 10, 739-743. (Pubitemid 38937640)
49. Tallam, L. S., Stec, D. E., Willis, M. A., da Silva, A. A., and, Hall, J. E., (2005) Melanocortin-4 receptor-deficient mice are not hypertensive or salt-sensitive despite obesity, hyperinsulinemia, and hyperleptinemia. Hypertension 46, 326-332. (Pubitemid 41099165)
50. Tallam, L. S., da Silva, A. A., and, Hall, J. E., (2006) Melanocortin-4 receptor mediates chronic cardiovascular and metabolic actions of leptin. Hypertension 48, 58-64. (Pubitemid 44297525)
51. da Silva, A.A., do Carmo, J. M., Kanyicska, B., Dubinion, J., Brandon, E., et al. (2008) Endogenous melanocortin system activity contributes to the elevated arterial pressure in spontaneously hypertensive rats. Hypertension 51, 884-890. (Pubitemid 351654700)
52. Kievit, P., Halem, H., Marks, D. L., Dong, J. Z., Glavas, M. M., et al. (2013) Chronic treatment with a melanocortin 4 receptor agonist causes weight loss, reduces insulin resistance, and improves cardiovascular function in diet-induced obese Rhesus Macaques. Diabetes 62, 490-497.
53. Greenfield, J. R., (2011) Melanocortin signaling and the regulation of blood pressure in human obesity. J. Neuroendocrinol. 23, 186-193.
54. Sayk, F., Heutling, D., Dodt, C., Iwen, K. A., Wellhoner, J. P., et al. (2002) Sympathetic function in human carriers of melanocortin-4 receptor gene mutations. J. Clin. Endocrinol. Metab. 95, 1998-2002.
55. Greenfield, J. R., Miller, J. W., Keogh, J. M., Henning, E., Satterwhite, J. H., et al. (2009) Modulation of blood pressure by central melanocortinergic pathways. N. Engl. J. Med. 360, 44-52.
56. Balthasar, N., Dalgaard, L. T., Lee, C. E., Yu, J., Funahashi, H., et al. (2005) Divergence control of melanocortin pathways in the control of food intake and energy expenditure. Cell 123, 493-505. (Pubitemid 41546678)
57. do Carmo, J. M., da Silva, A. A., Rushing, J. S., Dubinion, J., Hall, M., et al. (2011) Differential control of appetite and cardiovascular function after selective rescue of melanocortin-4 receptor in proopiomelanocortin neurons. Hypertension 12, 380.
58. do Carmo, J. M., da Silva, A. A., Rushing, J. S., and, Hall, J. E., (2012) Activation of the central melanocortin system contributes to the increased arterial pressure in obese Zucker rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 302, R561-R567.
59. Ma, X., Zubcevic, L., and, Ashcroft, F. M., (2008) Glucose regulates the effects of leptin on hypothalamic POMC neurons. Proc. Natl. Acad. Sci. USA. 105, 9811-9816. (Pubitemid 352031382)
60. Plum, L., Belgardt, B., and, Bruming, J., (2006) Central insulin action in energy and glucose homeostasis. J. Clin. Invest. 116, 1761-1766. (Pubitemid 44033295)
61. Batterham, R. L., Cowley, M. A., Small, C. J., Herzog, H., Cohen, M. A., et al. (2002) Gut hormone PYY (3-36) physiologically inhibits food intake. Nature 418, 650-654.
62. Blum, M., Roberts, J. L., and, Wardlaw, S.L., (1989). Androgen regulation of proopiomelanocortin gene expression and peptide content in the basal hypothalamus. Endocrinology 124, 2283-2288. (Pubitemid 19132028)
63. Gao, Q., Mezei, G., Nie, Y., Choi, C. S., Bechmann, I., et al. (2007) Anorectic estrogen mimics leptin's effect on rewiring of melanocortin cells and Stat3 signaling in obese animals. Nat. Med. 13, 89-94. (Pubitemid 46067391)
64. Jo, Y. H., Su, Y., Gutierrez-Juarez, G., and, Chua, S., (2009) Oleic acid directly regulates POMC neuron excitability in the hypothalamus. J. Neurophysiol. 101, 2305-2316.
65. Nicholson, J. R., Peter, J. C., Lecourt, A. C., Barde, Y. A., and, Hofbauer, K. G., (2007) Melanocortin-4 receptor activation stimulates hypothalamic brain-derived neurotrophic factor release to regulate food intake, body temperature and cardiovascular function. J. Neuroendocrinol. 19, 974-982. (Pubitemid 350131084)
66. Shimizu, H., Inoue, K., and, Mori, M., (2007) The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure. J. Endocrinol. 193, 1-9. (Pubitemid 46638526)
67. Tolson, K. P., GEmelli, T., Elmquist, J. K., Zinn, A. R., and, Kublaoui, B. M., (2010) Postnatal Sim1 deficiency causes hyperphagic obesity and reduced MC4R and oxytocin expression. J. Neurosci. 10, 3803-3812.