Leptin As a Mediator of Obesity-Induced Hypertension

Overview

Journal Curr Obes Rep

Specialty Endocrinology

Date 2016 Sep 26

PMID 27665107

Citations 60

Authors

Balyssa B Bell

Kamal Rahmouni

Affiliations

Soon will be listed here.

Abstract

Hypertension and associated cardiovascular diseases represent the most common health complication of obesity and the leading cause of morbidity and mortality in overweight and obese patients. Emerging evidence suggests a critical role for the central nervous system particularly the brain action of the adipocyte-derived hormone leptin in linking obesity and hypertension. The preserved ability of leptin to cause cardiovascular sympathetic nerve activation despite the resistance to the metabolic actions of the hormone appears essential in this pathological process. This review describes the evidence supporting the neurogenic bases for obesity-associated hypertension with a particular focus on the neuronal and molecular signaling pathways underlying leptin's effects on sympathetic nerve activity and blood pressure.

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References

Robinson M, Scheuermann-Freestone M, Leeson P, Channon K, Clarke K, Neubauer S . Uncomplicated obesity is associated with abnormal aortic function assessed by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2008; 10:10. PMC: 2265704. DOI: 10.1186/1532-429X-10-10. View

Muntzel M, Al-Naimi O, Barclay A, Ajasin D . Cafeteria diet increases fat mass and chronically elevates lumbar sympathetic nerve activity in rats. Hypertension. 2012; 60(6):1498-502. PMC: 3535318. DOI: 10.1161/HYPERTENSIONAHA.112.194886. View

Cnop M, Landchild M, Vidal J, Havel P, Knowles N, Carr D . The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations : distinct metabolic effects of two fat compartments. Diabetes. 2002; 51(4):1005-15. DOI: 10.2337/diabetes.51.4.1005. View

Hubert H, Feinleib M, MCNAMARA P, CASTELLI W . Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation. 1983; 67(5):968-77. DOI: 10.1161/01.cir.67.5.968. View

Lim K, Barzel B, Burke S, Armitage J, Head G . Origin of Aberrant Blood Pressure and Sympathetic Regulation in Diet-Induced Obesity. Hypertension. 2016; 68(2):491-500. DOI: 10.1161/HYPERTENSIONAHA.116.07461. View

Gao Q, Wolfgang M, Neschen S, Morino K, Horvath T, Shulman G . Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. Proc Natl Acad Sci U S A. 2004; 101(13):4661-6. PMC: 384803. DOI: 10.1073/pnas.0303992101. View

Henegar J, Zhang Y, De Rama R, Hata C, Hall M, Hall J . Catheter-based radiorefrequency renal denervation lowers blood pressure in obese hypertensive dogs. Am J Hypertens. 2014; 27(10):1285-92. PMC: 4184388. DOI: 10.1093/ajh/hpu048. View

Aizawa-Abe M, Ogawa Y, Masuzaki H, Ebihara K, Satoh N, Iwai H . Pathophysiological role of leptin in obesity-related hypertension. J Clin Invest. 2000; 105(9):1243-52. PMC: 315441. DOI: 10.1172/JCI8341. View

Alvarez G, Beske S, Ballard T, Davy K . Sympathetic neural activation in visceral obesity. Circulation. 2002; 106(20):2533-6. DOI: 10.1161/01.cir.0000041244.79165.25. View

10.

Ozata M, Ozdemir I, Licinio J . 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,.... J Clin Endocrinol Metab. 1999; 84(10):3686-95. DOI: 10.1210/jcem.84.10.5999. View

11.

Cota D, Proulx K, Smith K, Kozma S, Thomas G, Woods S . Hypothalamic mTOR signaling regulates food intake. Science. 2006; 312(5775):927-30. DOI: 10.1126/science.1124147. View

12.

Masuo K, Mikami H, Ogihara T, Tuck M . Differences in mechanisms between weight loss-sensitive and -resistant blood pressure reduction in obese subjects. Hypertens Res. 2001; 24(4):371-6. DOI: 10.1291/hypres.24.371. View

13.

Bjorbaek C, Elmquist J, Frantz J, Shoelson S, Flier J . Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell. 1998; 1(4):619-25. DOI: 10.1016/s1097-2765(00)80062-3. View

14.

Tallam L, Stec D, Willis M, da Silva A, Hall J . Melanocortin-4 receptor-deficient mice are not hypertensive or salt-sensitive despite obesity, hyperinsulinemia, and hyperleptinemia. Hypertension. 2005; 46(2):326-32. DOI: 10.1161/01.HYP.0000175474.99326.bf. View

15.

Garrison R, Kannel W, Stokes 3rd J, CASTELLI W . Incidence and precursors of hypertension in young adults: the Framingham Offspring Study. Prev Med. 1987; 16(2):235-51. DOI: 10.1016/0091-7435(87)90087-9. View

16.

Armitage J, Burke S, Prior L, Barzel B, Eikelis N, Lim K . Rapid onset of renal sympathetic nerve activation in rabbits fed a high-fat diet. Hypertension. 2012; 60(1):163-71. DOI: 10.1161/HYPERTENSIONAHA.111.190413. View

17.

Williams I, Chowienczyk P, Wheatcroft S, Patel A, A Sherwood R, Momin A . Endothelial function and weight loss in obese humans. Obes Surg. 2005; 15(7):1055-60. DOI: 10.1381/0960892054621134. View

18.

Harlan S, Morgan D, Dellsperger D, Myers Jr M, Mark A, Rahmouni K . Cardiovascular and sympathetic effects of disrupting tyrosine 985 of the leptin receptor. Hypertension. 2011; 57(3):627-32. PMC: 3072273. DOI: 10.1161/HYPERTENSIONAHA.110.166538. View

19.

Harlan S, Guo D, Morgan D, Fernandes-Santos C, Rahmouni K . Hypothalamic mTORC1 signaling controls sympathetic nerve activity and arterial pressure and mediates leptin effects. Cell Metab. 2013; 17(4):599-606. PMC: 3657313. DOI: 10.1016/j.cmet.2013.02.017. View

20.

Pedroso J, Buonfiglio D, Cardinali L, Furigo I, Ramos-Lobo A, Tirapegui J . Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity. Mol Metab. 2014; 3(6):608-18. PMC: 4142399. DOI: 10.1016/j.molmet.2014.06.001. View