J. Wilson et al., HEPATIC FATTY-ACID SYNTHASE GENE-TRANSCRIPTION IS INDUCED BY A DIETARY COPPER DEFICIENCY, American journal of physiology: endocrinology and metabolism, 35(6), 1997, pp. 1124-1129
A dietary copper (Cu) deficiency is associated with a twofold increase
in hepatic fatty acid biosynthesis. We hypothesized that the inductio
n of hepatic lipogenesis associated with a dietary Cu deficiency refle
cted 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 mu g Cu/g)
or Cu adequate (CuA; 5.0 mu g Cu/g). The CuD diet increased FAS enzym
atic activity twofold (P < 0.05). This rise in enzymatic activity was
accompanied by a threefold increase in FAS mRNA and a 2.5-fold increas
e 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 suppresse
d by treating CuD rats with L-buthionine sulfoximine, the induction of
FAS expression was completely prevented. Similarly, feeding N-acetylc
ysteine to CuA rats increased hepatic GSH levels 2.5-fold, and this wa
s accompanied by a significant induction in FAS expression. These data
indicate that the increase in hepatic lipogenesis associated with a C
u deficiency reflects an induction in hepatic lipogenic gene transcrip
tion (i.e., FAS) and that the rate of gene transcription may be depend
ent on hepatic thiol redox.