RGD Reference Report - Leptin induces nitric oxide-mediated inhibition of lipolysis and glyceroneogenesis in rat white adipose tissue. - Rat Genome Database

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Leptin induces nitric oxide-mediated inhibition of lipolysis and glyceroneogenesis in rat white adipose tissue.

Authors: Niang, F  Benelli, C  Ribiere, C  Collinet, M  Mehebik-Mojaat, N  Penot, G  Forest, C  Jaubert, AM 
Citation: Niang F, etal., J Nutr. 2011 Jan;141(1):4-9. Epub 2010 Nov 10.
RGD ID: 5128556
Pubmed: (View Article at PubMed) PMID:21068181
DOI: Full-text: DOI:10.3945/jn.110.125765

Leptin is secreted by white adipose tissue (WAT) and induces lipolysis and nonesterified fatty acid (NEFA) oxidation. During lipolysis, NEFA efflux is the result of triglyceride breakdown, NEFA oxidation, and re-esterification via glyceroneogenesis. Leptin's effects on glyceroneogenesis remain unexplored. We investigated the effect of a long-term treatment with leptin at a physiological concentration (10 mug/L) on lipolysis and glyceroneogenesis in WAT explants and analyzed the underlying mechanisms. Exposure of rat WAT explants to leptin for 2 h resulted in increased NEFA and glycerol efflux. However, a longer treatment with leptin (18 h) did not affect NEFA release and reduced glycerol output. RT-qPCR showed that leptin significantly downregulated the hormone-sensitive lipase (HSL), cytosolic phosphoenolpyruvate carboxykinase (Pck1), and PPARgamma genes. In agreement with its effect on mRNA, leptin also decreased the levels of PEPCK-C and HSL proteins. Glyceroneogenesis, monitored by [1-(14) C] pyruvate incorporation into lipids, was reduced. Because leptin increases nitric oxide (NO) production in adipocytes, we explored the role of NO in the leptin signaling pathway. Pretreatment of explants with the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester eliminated the effect of leptin on lipolysis, glyceroneogenesis, and expression of the HSL, Pck1, and PPARgamma genes. The NO donor S-nitroso-N-acetyl-DL penicillamine mimicked leptin effects, thus demonstrating the role of NO in these pathways. The inverse time-dependent action of leptin on WAT is consistent with a process that limits NEFA re-esterification and energy storage while reducing glycerol release, thus preventing hypertriglyceridemia.


Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Lep  (leptin)

Additional Information