title: Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity.
abstract: To determine whether increased lipogenesis contributes to human obesity, we measured (postabsorptive state), in lean and obese subjects, lipid synthesis (deuterated water method) and the mRNA concentration (RT-competitive PCR) in subcutaneous adipose tissue of fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1c. Before energy restriction, obese subjects had an increased contribution of hepatic lipogenesis to the circulating triglyceride pool (14.5 +/- 1.3 vs. 7.5 +/- 1.9%, P < 0.01) without enhancement of cholesterol synthesis. This increased hepatic lipogenesis represented an excess of 2-5 g/day of triglycerides, which would represent 0.7-1.8 kg on a yearly basis. The lipogenic capacity of adipose tissue appeared, on the contrary, decreased with lower FAS mRNA levels (P < 0.01) and a trend for decreased SREBP-1c mRNA (P = 0.06). Energy restriction in obese patients decreased plasma insulin (P < 0.05) and leptin (P < 0.05) and normalized hepatic lipogenesis. FAS mRNA levels were unchanged, whereas SREBP-1c increased. In conclusion, subjects with established obesity have an increased hepatic lipogenesis that could contribute to their excessive fat mass but no evidence for an increased lipogenic capacity of adipose tissue.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 499, Faculté RTH Laennec, 69008 Lyon, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Diraison
authors.forename: Eric
authors.initials: E
authors.lastname: Dusserre
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Monique
authors.initials: M
authors.lastname: Sothier
authors.forename: Michel
authors.initials: M
authors.lastname: Beylot
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology*; D000328:Adult; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D064429:Fatty Acid Synthases / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D051780:Sterol Regulatory Element Binding Protein 1; D013851:Thinness; D014157:Transcription Factors
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D008055:Lipids; D012333:RNA, Messenger; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D064429:Fatty Acid Synthases