Acute stimulation of glucose metabolism in mice by leptin treatment

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Leptin is an adipocyte hormone that functions as an afferent signal in a negative feedback loop regulating body weight1,2,3,4, and acts by interacting with a receptor in the hypothalamus and other tissues5,6. Leptin treatment has potent effects on lipid metabolism, and leads to a large, specific reduction of adipose tissue mass after several days1,4. Here we show that leptin also acts acutely to increase glucose metabolism, although studies of leptin's effect on glucose metabolism have typically been confounded by the weight-reducing actions of leptin treatment, which by itself could affect glucose homoeostasis1,2,3. We have demonstrated acute in vivo effects of intravenous and intracerebroventricular administrations of leptin on glucose metabolism. A five-hour intravenous infusion of leptin into wild-type mice increased glucose turnover and glucose uptake, but decreased hepatic glycogen content. The plasma levels of insulin and glucose did not change. Similar effects were observed after both intravenous and intracerebroventricular infusion of leptin, suggesting that effects of leptin on glucose metabolism are mediated by the central nervous system (CNS). These data indicate that leptin induces a complex metabolic response with effects on glucose as well as lipid metabolism. This response is unique to leptin, which suggests that new efferent signals emanate from the CNS after leptin treatment.

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Figure 1: Experimental protocols using C57BL/6J +/+ lean mice.
Figure 2: Glucose turnover in C57BL/6J +/+ lean mice after IV or ICV leptin infusion.
Figure 3: Individual tissue glucose uptake in C57BL/6J +/+ lean mice after IV or ICV leptin infusion.


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We thank E. B. Katz, C. Vaisse, J. Li and T. S. Tsao for discussions; J. Blaire-West and D. A. Denton for help with the ICV surgery; S. Korres for helping to prepare the manuscript; and Amgen for recombinant leptin. This work was supported by grants from the NIH (J.M.F. and M.J.C.), Pew Charitable Trust (M.J.C.), Juvenile Diabetes Foundation International (R.B.), the Philippe Foundation (R.B.) and the Manpei Suzuki Diabetes Foundation (S.K.).

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Correspondence to Maureen J. Charron.

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Kamohara, S., Burcelin, R., Halaas, J. et al. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389, 374–377 (1997) doi:10.1038/38717

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