Hepatic fatty acid synthase gene transcription is induced by a dietary copper deficiency.
A dietary copper (Cu) deficiency is associated with a twofold increase in hepatic fatty acid biosynthesis. We hypothesized that the induction of hepatic lipogenesis associated with a dietary Cu deficiency reflected an enhanced expression of genes encoding lipogenic enzymes, i.e., fatty acid synthase (FAS). Male weanling rats were pair-meal fed for 42 days a high-sucrose diet that was Cu deficient (CuD; 0.7 microgram Cu/g) or Cu adequate (CuA; 5.0 micrograms Cu/g). The CuD diet increased FAS enzymatic activity twofold (P < 0.05). This rise in enzymatic activity was accompanied by a threefold increase in FAS mRNA and a 2.5-fold increase in FAS gene transcription (P < 0.05). Neither the mRNA abundance nor the rate of gene transcription for phosphoenolpyruvate carboxykinase or beta-actin was affected by the CuD diet. The induction of FAS gene transcription was associated with a 65-85% increase in hepatic reduced glutathione (GSH; P < 0.05). When hepatic GSH synthesis was suppressed by treating CuD rats with L-buthionine sulfoximine, the induction of FAS expression was completely prevented. Similarly, feeding N-acetylcysteine to CuA rats increased hepatic GSH levels 2.5-fold, and this was accompanied by a significant induction in FAS expression. These data indicate that the increase in hepatic lipogenesis associated with a Cu deficiency reflects an induction in hepatic lipogenic gene transcription (i.e., FAS) and that the rate of gene transcription may be dependent on hepatic thiol redox.
Wilson
J
J
Department of Food Science and Human Nutrition, Colorado State University, Fort Collins 80523, USA.
Kim
S
S
Allen
K G
KG
Baillie
R
R
Clarke
S D
SD
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D003300:Copper / Q000172:deficiency* / Q000378:metabolism; D004790:Enzyme Induction; D064429:Fatty Acid Synthases / Q000096:biosynthesis*; D005978:Glutathione / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic; D015032:Zinc / Q000378:metabolism
D000199:Actins; D012333:RNA, Messenger; D003300:Copper; D007501:Iron; D064429:Fatty Acid Synthases; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005978:Glutathione; D015032:Zinc