Selective up-regulation of fatty acid uptake by adipocytes characterizes both genetic and diet-induced obesity in rodents.
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.
Berk
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Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York 10029, USA. paul_berk@smtplink.mssm.edu
Zhou
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Kiang
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Stump
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Fan
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Bradbury
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D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D004032:Diet; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D019301:Oleic Acid / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D015854:Up-Regulation; D015430:Weight Gain
D004042:Dietary Fats, Unsaturated; D020738:Leptin; D019301:Oleic Acid