Decreased fatty acid synthesis due to mitochondrial uncoupling in adipose tissue.
Synthesis of fatty acid (FA) in adipose tissue requires cooperation of mitochondrial and cytoplasmic enzymes. Mitochondria are required for the production of ATP and they also support the formation of acetyl-CoA and NADPH in cytoplasm. Since cellular levels of all these metabolites depend on the efficiency of mitochondrial energy conversion, mitochondrial proton leak via uncoupling proteins (UCPs) could modulate FA synthesis. In 3T3-L1 adipocytes, 2,4-dinitrophenol depressed the synthesis of FA 4-fold while increasing FA oxidation 1. 5-fold and the production of lactate 14-fold. Inhibition of FA synthesis in 3T3-L1 adipocytes was proportional to the decrease in mitochondrial membrane potential. FA synthesis from D-[U-(14)C] glucose was reduced up to fourfold by ectopic UCP1 in the white fat of transgenic aP2-Ucp1 mice, reflecting the magnitude of UCP1 expression in different fat depots and the reduction of adiposity. Transcript levels for lipogenic enzymes were lower in the white fat of the transgenic mice than in the control animals. Our results show that uncoupling of oxidative phosphorylation depresses FA synthesis in white fat. Reduction of adiposity via mitochondrial uncoupling in white fat not only reflects increased energy expenditure, but also decreased in situ lipogenesis.
Rossmeisl
M
M
Department of Adipose Tissue Biology, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Syrový
I
I
Baumruk
F
F
Flachs
P
P
Janovská
P
P
Kopecký
J
J
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004734:Energy Metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D015870:Gene Expression; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D024101:Mitochondrial Proteins; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1