Selective up-regulation of fatty acid uptake by adipocytes characterizes both genetic and diet-induced obesity in rodents

J Biol Chem. 1999 Oct 1;274(40):28626-31. doi: 10.1074/jbc.274.40.28626.

Abstract

Long chain fatty acid transport is selectively up-regulated in adipocytes of Zucker fatty rats, diverting fatty acids from sites of oxidation toward storage in adipose tissue. To determine whether this is a general feature of obesity, we studied [(3)H]oleate uptake by adipocytes and hepatocytes from 1) homozygous male obese (ob), diabetic (db), fat (fat), and tubby (tub) mice and from 2) male Harlan Sprague-Dawley rats fed for 7 weeks a diet containing 55% of calories from fat. V(max) and K(m) were compared with controls of the appropriate background strain (C57BL/6J or C57BLKS) or diet (13% of calories from fat). V(max) for adipocyte fatty acid uptake was increased 5-6-fold in ob, db, fat, and tub mice versus controls (p < 0.001), whereas no differences were seen in the corresponding hepatocytes. Similar changes occurred in fat-fed rats. Of three membrane fatty acid transporters expressed in adipocytes, plasma membrane fatty acid-binding protein mRNA was increased 9-11-fold in ob and db, which lack a competent leptin/leptin receptor system, but was not increased in fat and tub, i.e. in strains with normal leptin signaling capability; fatty acid translocase mRNA was increased 2.2-6.5-fold in tub, ob, and fat adipocytes, but not in db adipocytes; and only marginal changes in fatty acid transport protein 1 mRNA were found in any of the mutant strains. Adipocyte fatty acid uptake is generally increased in murine obesity models, but up-regulation of individual transporters depends on the specific pathophysiology. Leptin may normally down-regulate expression of plasma membrane fatty acid binding protein.

Publication types

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

MeSH terms

  • Adipocytes / metabolism*
  • Animals
  • Blotting, Northern
  • Diet*
  • Dietary Fats, Unsaturated / administration & dosage
  • Leptin / genetics
  • Leptin / metabolism
  • Liver / cytology
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Obesity / etiology
  • Obesity / genetics
  • Obesity / metabolism*
  • Oleic Acid / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Species Specificity
  • Up-Regulation*
  • Weight Gain

Substances

  • Dietary Fats, Unsaturated
  • Leptin
  • Oleic Acid