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Diabetes 54:2012-2018, 2005
© 2005 by the American Diabetes Association, Inc.

Role of Selective Leptin Resistance in Diet-Induced Obesity Hypertension

Kamal Rahmouni1,2, Donald A. Morgan1,2, Gina M. Morgan1,2, Allyn L. Mark1,2, and William G. Haynes1,2

1 Hypertension Genetics Specialized Center of Research, Cardiovascular Center, University of Iowa, Iowa City, Iowa
2 Department of Internal Medicine, University of Iowa, Iowa City, Iowa

Leptin is an adipocyte-derived hormone that plays a key role in the regulation of body weight through its actions on appetite and metabolism. Leptin also increases sympathetic nerve activity (SNA) and blood pressure. We tested the hypothesis that diet-induced obesity is associated with resistance to the metabolic actions of leptin but preservation of its renal SNA and arterial pressure effects, leading to hypertension. Mice were fed a high-fat diet for 10 weeks to induce moderate obesity. The decrease in food intake and body weight induced by intraperitoneal or intracerebroventricular leptin was significantly attenuated in the obese mice. Regional SNA responses to leptin were differentially altered in diet-induced obese mice. Renal SNA response to leptin was preserved, whereas lumbar and brown adipose tissue SNA responses were attenuated in obese mice. Radiotelemetric arterial pressure was ~10 mmHg higher in obese mice. Furthermore, the increase in arterial pressure in response to long-term (12 days) leptin treatment was preserved in obese mice. Thus, mice with diet-induced obesity exhibit circulating hyperleptinemia and resistance to the metabolic actions of leptin. However, there is preservation of the renal sympathetic and arterial pressure responses to leptin, which represent a potential mechanism for the adverse cardiovascular consequences of obesity.

Address correspondence and reprint requests to Kamal Rahmouni, PhD, Cardiovascular Research Center, 524 MRC, University of Iowa, Iowa City, IA 52242. E-mail: kamal-rahmouni{at}uiowa.edu

Abbreviations: BAT, brown adipose tissue; SNA, symapathetic nerve activity


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