Induction of leptin receptor expression in the liver by leptin and food deprivation

J Biol Chem. 2005 Mar 18;280(11):10034-9. doi: 10.1074/jbc.M413684200. Epub 2005 Jan 11.

Abstract

Leptin resistance is a common feature of obesity and the metabolic syndrome. However, the regulated expression of the leptin receptor (Ob-R) has not been studied in detail. Expression profiling of liver mRNA in leptin-treated wild-type mice revealed a marked increase in leptin receptor mRNA levels, which had not previously been described. This was confirmed by isoform-specific real-time PCR, which showed a >25-fold increase in the mRNAs encoding the short forms (Ob-Ra, Ob-Rc) and a >10-fold increase in the mRNA encoding the long (Ob-Rb) form of the leptin receptor in liver. In parallel, we also observed induction of plasma-soluble leptin receptor (SLR) protein by leptin administration, pair feeding, and short term food restriction. However, induction of SLR by leptin is abolished in mice with selective deletion of Ob-R from liver using Cre-LoxP technology. These data suggest that the liver is a major source of Ob-R mRNA expression under conditions of negative energy balance. Membrane-bound Ob-R is then shed into the circulation as SLR. Our study thus reveals an unexpected role of the liver in modulating total circulating leptin levels and possibly its biological activity.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Northern
  • Body Weight
  • Cell Membrane / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Food Deprivation*
  • Leptin / metabolism*
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Placenta / metabolism
  • Protein Isoforms
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / biosynthesis*
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Receptors, Leptin
  • Recombinant Proteins / chemistry
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors

Substances

  • Leptin
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Leptin
  • Recombinant Proteins
  • leptin receptor, mouse
  • RNA