PPAR-gamma activation mediates adipose depot-specific effects on gene expression and lipoprotein lipase activity: mechanisms for modulation of postprandial lipemia and differential adipose accretion.
This study sought to determine whether the adipose depot-specific (subcutaneous [SF] vs. visceral [VF]) action of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists on fat deposition extends to the expression of lipoprotein lipase (LPL) and other key adipose lipid metabolism genes, and whether changes in LPL impact triglyceridemia. Rats were fed a standard diet or an obesity-promoting diet for 3 weeks, with or without treatment with COOH, a nonthiazolidinedione PPAR-gamma agonist. Treatment effects were essentially similar in both dietary cohorts. COOH did not affect weight gain, but increased SF (inguinal) fat mass twofold and reduced VF (retroperitoneal) accretion by half. Corresponding depot-specific alterations were observed in mRNA levels of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD-1) and the thermogenic modulator uncoupling protein 1 (UCP-1). COOH increased brown adipose tissue (BAT) weight and LPL availability by five- to eightfold. In rats refed standard diet after a 24-h fast, COOH reduced the insulin excursion by half. The agonist increased SF LPL activity and mRNA levels, but had no effect on VF LPL. The two- to threefold postprandial increase in plasma triglycerides (TGs) was abrogated in COOH-treated rats, likely in part because of increased LPL in SF and BAT. Thus PPAR-gamma agonist treatment had a powerful, site-specific effect on adipose metabolism and lipid deposition, and greatly impacted the postprandial handling of TG-rich lipoproteins. These depot-specific effects may be mediated by differential regulation of key metabolic genes, including LPL, 11beta-HSD-1, and UCP-1.
Laplante
Mathieu
M
Department of Anatomy and Physiology, Laval Hospital Research Center, School of Medicine, Laval University, Québec, Canada.
Sell
Henrike
H
MacNaul
Karen L
KL
Richard
Denis
D
Berger
Joel P
JP
Deshaies
Yves
Y
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000033:anatomy & histology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D017931:DNA Primers; D004032:Diet; D004041:Dietary Fats; D019422:Dietary Sucrose; D002149:Energy Intake; D005786:Gene Expression Regulation / Q000502:physiology*; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics*; D007473:Ion Channels; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins; D009929:Organ Size; D019518:Postprandial Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000502:physiology*; D022722:Thermogenesis; D014157:Transcription Factors / Q000819:agonists / Q000502:physiology*; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D017931:DNA Primers; D004041:Dietary Fats; D019422:Dietary Sucrose; D007473:Ion Channels; D008055:Lipids; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D008071:Lipoprotein Lipase