Mechanisms of the depot specificity of peroxisome proliferator-activated receptor gamma action on adipose tissue metabolism.
In this study, we aimed to establish the mechanisms whereby peroxisome proliferator-activated receptor gamma (PPARgamma) agonism brings about redistribution of fat toward subcutaneous depots and away from visceral fat. In rats treated with the full PPARgamma agonist COOH (30 mg x kg(-1) x day(-1)) for 3 weeks, subcutaneous fat mass was doubled and that of visceral fat was reduced by 30% relative to untreated rats. Uptake of triglyceride-derived nonesterified fatty acids was greatly increased in subcutaneous fat (14-fold) and less so in visceral fat (4-fold), with a concomitant increase, restricted to subcutaneous fat only, in mRNA levels of the uptake-, retention-, and esterification-promoting enzymes lipoprotein lipase, aP2, and diacylglycerol acyltransferase 1. Basal lipolysis and fatty acid recycling were stimulated by COOH in both subcutaneous fat and visceral fat, with no frank quantitative depot specificity. The agonist increased mRNA levels of enzymes of fatty acid oxidation and thermogenesis much more strongly in visceral fat than in subcutaneous fat, concomitantly with a stronger elevation in O2 consumption in the former than in the latter. Mitochondrial biogenesis was stimulated equally in both depots. These findings demonstrate that PPARgamma agonism redistributes fat by stimulating the lipid uptake and esterification potential in subcutaneous fat, which more than compensates for increased O2 consumption; conversely, lipid uptake is minimally altered and energy expenditure is greatly increased in visceral fat, with consequent reduction in fat accumulation.
Laplante
Mathieu
M
Laval Hospital Research Centre, Laval University, Quebec, QC, Canada G1V 4G5.
Festuccia
William T
WT
Soucy
Geneviève
G
Gélinas
Yves
Y
Lalonde
Josée
J
Berger
Joel P
JP
Deshaies
Yves
Y
D000085:Acetates / Q000494:pharmacology; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000378:metabolism; D017667:Adipocytes / Q000648:ultrastructure; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D050152:Intra-Abdominal Fat / Q000033:anatomy & histology / Q000187:drug effects; D007473:Ion Channels / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050151:Subcutaneous Fat / Q000033:anatomy & histology / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism; D000071256:Uncoupling Protein 1
C483845:2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid; D000085:Acetates; D005227:Fatty Acids; D007211:Indoles; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002334:Carnitine O-Palmitoyltransferase; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D017346:Protein Serine-Threonine Kinases; D005990:Glycerol