RGD Reference Report - Liporegulation in diet-induced obesity. The antisteatotic role of hyperleptinemia. - Rat Genome Database

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Liporegulation in diet-induced obesity. The antisteatotic role of hyperleptinemia.

Authors: Lee, Y  Wang, MY  Kakuma, T  Wang, ZW  Babcock, E  McCorkle, K  Higa, M  Zhou, YT  Unger, RH 
Citation: Lee Y, etal., J Biol Chem 2001 Feb 23;276(8):5629-35.
RGD ID: 62400
Web Url: http://www.jbc.org/cgi/content/full/276/8/5629
Pubmed: PMID:11096093   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M008553200   (Journal Full-text)

To test the hypothesis that the physiologic liporegulatory role of hyperleptinemia is to prevent steatosis during caloric excess, we induced obesity by feeding normal Harlan Sprague-Dawley rats a 60% fat diet. Hyperleptinemia began within 24 h and increased progressively to 26 ng/ml after 10 weeks, correlating with an approximately 150-fold increase in body fat (r = 0.91, p < 0.0001). During this time, the triacylglycerol (TG) content of nonadipose tissues rose only 1-2.7-fold implying antisteatotic activity. In rodents without leptin action (fa/fa rats and ob/ob and db/db mice) receiving a 6% fat diet, nonadipose tissue TG was 4-100 times normal. In normal rats on a 60% fat diet, peroxisome proliferator-activated receptor alpha protein and liver-carnitine palmitoyltransferase-1 (l-CPT-1) mRNA increased in liver. In their pancreatic islets, fatty-acid oxidation increased 30% without detectable increase in the expression of peroxisome proliferator-activated receptor-alpha or oxidative enzymes, whereas lipogenesis from [14C]glucose was slightly below that of the 4% fat-fed rats (p < 0.05). Tissue-specific overexpression of wild-type leptin receptors in the livers of fa/fa rats, in which marked steatosis is uniformly present, reduced TG accumulation in liver but nowhere else. We conclude that a physiologic role of the hyperleptinemia of caloric excess is to protect nonadipocytes from steatosis and lipotoxicity by preventing the up-regulation of lipogenesis and increasing fatty-acid oxidation.

Objects referenced in this article
Gene Lepr leptin receptor Rattus norvegicus

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