Acquirement of brown fat cell features by human white adipocytes.
Obesity, i.e. an excess of white adipose tissue (WAT), predisposes to the development of type 2 diabetes and cardiovascular disease. Brown adipose tissue is present in rodents but not in adult humans. It expresses uncoupling protein 1 (UCP1) that allows dissipation of energy as heat. Peroxisome proliferator-activated receptor gamma (PPAR gamma) and PPAR gamma coactivator 1 alpha (PGC-1 alpha) activate mouse UCP1 gene transcription. We show here that human PGC-1 alpha induced the activation of the human UCP1 promoter by PPAR gamma. Adenovirus-mediated expression of human PGC-1 alpha increased the expression of UCP1, respiratory chain proteins, and fatty acid oxidation enzymes in human subcutaneous white adipocytes. Changes in the expression of other genes were also consistent with brown adipocyte mRNA expression profile. PGC-1 alpha increased the palmitate oxidation rate by fat cells. Human white adipocytes can therefore acquire typical features of brown fat cells. The PPAR gamma agonist rosiglitazone potentiated the effect of PGC-1 alpha on UCP1 expression and fatty acid oxidation. Hence, PGC-1 alpha is able to direct human WAT PPAR gamma toward a transcriptional program linked to energy dissipation. However, the response of typical white adipocyte targets to rosiglitazone treatment was not altered by PGC-1 alpha. UCP1 mRNA induction was shown in vivo by injection of the PGC-1 alpha adenovirus in mouse white fat. Alteration of energy balance through an increased utilization of fat in WAT may be a conceivable strategy for the treatment of obesity.
Tiraby
Claire
C
Unité de Recherches sur les Obésités, Institut National de la Santé et de la Recherche Médicale Unité 586, Institut Louis Bugnard, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, 31403 Toulouse, France.
Tavernier
Geneviève
G
Lefort
Corinne
C
Larrouy
Dominique
D
Bouillaud
Frédéric
F
Ricquier
Daniel
D
Langin
Dominique
D
D000256:Adenoviridae; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D006801:Humans; D007473:Ion Channels; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D008954:Models, Biological; D009765:Obesity / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D003574:Cytochrome c Group; D018076:DNA, Complementary; D007473:Ion Channels; D008164:Luminescent Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D014157:Transcription Factors; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D049452:Green Fluorescent Proteins; D019308:Palmitic Acid; D015500:Chloramphenicol O-Acetyltransferase; D010100:Oxygen