Liporegulation in Diet-induced Obesity: The antisteatotic role of hyperleptinemia

Young H Lee, May-Yun Wang, Tetsuya Kakuma, Zhuo Wei Wang, Evelyn E Babcock, Kay McCorkle, Moritake Higa, Yan Ting Zhou, Roger H Unger

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


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 ∼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 α 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-α 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.

Original languageEnglish (US)
Pages (from-to)5629-5635
Number of pages7
JournalJournal of Biological Chemistry
Issue number8
StatePublished - Feb 23 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Liporegulation in Diet-induced Obesity: The antisteatotic role of hyperleptinemia'. Together they form a unique fingerprint.

Cite this