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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/E630    most recent 00704.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shi, H. Articles by Seeley, R. J. Search for Related Content PubMed PubMed Citation Articles by Shi, H. Articles by Seeley, R. J.

Sexually different actions of leptin in proopiomelanocortin neurons to regulate glucose homeostasis

¹Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, Ohio; and ²Department of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois

Submitted 1 November 2007 ; accepted in final form 26 December 2007

Leptin regulates energy balance and glucose homeostasis, at least in part, via activation of receptors in the arcuate nucleus of the hypothalamus located in proopiomelanocortin (POMC) neurons. Females have greater sensitivity to central leptin than males, suggested by a greater anorectic effect of central leptin administration in females. We hypothesized that the regulation of energy balance and peripheral glucose homeostasis of female rodents would be affected to a greater extent than in males if the action of leptin in POMC neurons were disturbed. Male and female mice lacking leptin receptors only in POMC neurons gained significantly more body weight and accumulated more body fat. However, female mice gained disproportionately more visceral adiposity than males, and this appeared to be largely the result of differences in energy expenditure. When maintained on a high-fat diet (HFD), both male and female mutants had higher levels of insulin following exogenous glucose challenges. Chow- and HFD-fed males but not females had abnormal glucose disappearance curves following insulin administrations. Collectively, these data indicate that the action of leptin in POMC neurons is sexually different to influence the regulation of energy balance, fat distribution, and glucose homeostasis.

leptin receptor; energy balance; glucose tolerance; insulin sensitivity; fat distribution