NDLI: Site and mechanism of leptin action in a rodent form of congenital lipodystrophy

Content Provider	PubMed Central
Author	Esra, Asilmaz Cohen, Paul Miyazaki, Makoto Pawel, Dobrzyn Ueki, Kohjiro Fayzikhodjaeva, Gulnorakhon Soukas, Alexander A. Kahn, C. Ronald Ntambi, James M. Socci, Nicholas D. Friedman, Jeffrey M.
Copyright Year	2004
Abstract	Lipodystrophy is characterized by the complete or partial absence of adipose tissue, insulin resistance, hepatic steatosis, and leptin deficiency. Here, we show that low-dose central leptin corrects the insulin resistance and fatty liver of lipodystrophic aP2-nSREBP-1c mice, while the same dose given peripherally does not. Central leptin also repressed stearoyl-CoA desaturase-1 (SCD-1) RNA and enzymatic activity, which were increased in livers of lipodystrophic mice. aP2-nSREBP-1c mice homozygous for an SCD-1 deletion had markedly reduced hepatic steatosis, increased saturated fatty acids, decreased acetyl-CoA carboxylase activity, and decreased malonyl-CoA levels in the liver. Despite the reduction in hepatic steatosis, these mice remained diabetic. A leptin dose-response curve showed that subcutaneous leptin improved hyperglycemia and hyperinsulinemia in aP2-nSREBP-1c mice at doses that did not substantially alter hepatic steatosis or hepatic SCD enzymatic activity. Leptin treatment at this dose improved insulin-stimulated insulin receptor and insulin receptor substrate 2 (IRS-2) phosphorylation, IRS-2–associated PI3K activity, and Akt activity in liver. Together, these data suggest that CNS-mediated repression of SCD-1 contributes to leptin’s antisteatotic actions. Intracerebroventricular leptin improves glucose homeostasis by improving insulin signal transduction in liver, but in this case the effect appears to be independent of SCD-1.
Related Links	http://dx.doi.org/10.1172/jci200419511
Ending Page	424
Page Count	11
Starting Page	414
File Format	PDF
ISSN	00219738
Journal	Journal of Clinical Investigation
Issue Number	3
Volume Number	113
Language	English
Publisher	American Society for Clinical Investigation
Publisher Date	2004-02-01
Access Restriction	Open
Rights Holder	American Society for Clinical Investigation
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine

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