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Decreased fatty acid synthesis due to mitochondrial uncoupling in adipose tissue
Author(s) -
Rossmeisl Martin,
Syrový Ivo,
Baumruk Filip,
Flachs Pavel,
Janovska Petra,
Kopecký Jan
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.99-0965com
Subject(s) - thermogenin , lipogenesis , white adipose tissue , fatty acid synthesis , mitochondrion , oxidative phosphorylation , brown adipose tissue , adipose tissue , beta oxidation , atp synthase , medicine , chemistry , uncoupling protein , endocrinology , fatty acid , biochemistry , biology , enzyme
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 1.5fold 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., Syrový, I., Baumruk, F., Flachs, P., Janovská, P., Kopecký, J. Decreased fatty acid synthesis due to mitochondrial uncoupling in adipose tissue. FASEB J. 14, 1793–1800 (2000)