The protein product of the gene called leptin (leptos means thin) is considered to be the major player in the regulation of the body fat. Chen et al in the Dec 1996 issue of Proceedings of National Academy of Sciences provide further evidence for this role of leptin. Infusion of a recombinant adenovirus containing the rat leptin cDNA (AdCMV-leptin) to rats resulted in 30-50% loss of foot intake, minimal increase in weight, loss of body fat and a sustained hyperlipidemia over the study period. On the other hand, the control group of animals which were infused with saline or a recombinant virus containing the beta-galactosidase gene (AdCMV-beta-Gal) gained substantial amount of body weight,and retained about 50% of their body fat during the same period. These findings are supportive of the concept that leptin has lipoatrophic effect. These findings have been verified in a different study reported by Muzzin et al in the same issue of Proceedings of National Academy of Sciences. These authors reported that treatment of ob/ob mice which are genetically deficient in leptin with a recombinant adenovirus expressing the mouse leptin cDNA, resulted in reduction in food intake as well as body weight.

In the hyperleptinemic animals studied by Chen et al, the serum levels of plasma triglycerides and insulin levels were significantly lower than that found in the control group raising the possibility that leptin may play a role in regulating the insulin levels. Consistent with this hypothesis, Muzzin et al, reported that treatment of the ob/ob mice which exhibit a mild non-insulin-dependent diabetic phenotype, with leptin gene therapy led to the normalization of serum insulin levels and glucose tolerance. These studies suggest that leptin gene therapy may be used both for the control of body weight and in the management of non-insulin-dependent diabetes mellitus.

The effect of leptin does not seem to be confined to the regulation of body fat or insulin. Gainsford et al, found that both the mRNAs encoding long and short forms of the human leptin receptor were expressed in a diverse group of cells in the hemopoietic organs in both human and mouse. A subset of these cells were able to bind leptin. Leptin enhanced phagocytosis and cytokine production in these cells. These findings show that leptin is a cytokine which targets various cells in the body.

REFERENCES:

Guoxun Chen, Kazunori Koyama, Xue Yuan, Young Lee, Yan-Ting Zhou, Robert O'Doherty, Christopher B. Newgard, Roger H. Unger: Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy. Proc Natl Acad Sci USA 93, 14795-14799, 1996

Patrick Muzzin, Randy C. Eisensmith, Kenneth C. Copeland, Savio L. C. Woo: Correction of obesity and diabetes in genetically obese mice by leptin gene therapy, Proc Natl Acad Sci USA 93, 14804-14808, 1996

Timothy Gainsford, Tracy A. Willson, Donald Metcalf, Emanuela Handman, Clare McFarlane, Ashley Ng, Nicos A. Nicola, Warren S. Alexander, Douglas J. Hilton: Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci USA 93,14564-14568, 1996

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