The effect of leptin on Lep expression is tissue-specific and nutritionally regulated

Nat Med. 1999 Aug;5(8):895-9. doi: 10.1038/11335.


Leptin, the product of the Obese (Lep) gene, orchestrates behavioral and metabolic responses to nutrient intake. Here, we demonstrate tissue-specific autoregulation of Lep. Moderate increases in circulating leptin considerably decreased Lep expression in adipose tissue and induced lep expression in skeletal muscle, a tissue that normally does not express this gene. Changes in nutrient availability resulted in rapid alterations in Lep autoregulation. These findings demonstrate negative feedback regulation of Lep in fat, and indicate that leptin secretion can function as a vehicle of 'cross-talk' between adipose tissue and skeletal muscle, leading to tissue-specific modulation of the 'leptin signal'.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Blotting, Northern
  • Diet, Reducing
  • Eating / physiology
  • Feedback / physiology
  • Gene Expression Regulation / drug effects
  • Leptin
  • Male
  • Mice
  • Muscle, Skeletal / metabolism
  • Nutritional Status / physiology*
  • Organ Specificity
  • Protein Biosynthesis*
  • Proteins / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Zucker
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Leptin
  • Proteins
  • RNA, Messenger