Hepatic fatty acid synthase gene transcription is induced by a
dietary copper deficiency..
Wilson, John, Sangbae Kim, Kenneth G. D. Allen, Rebecca Baillie, and
Steven D. Clarke.
Department of Food Science and Human Nutrition, Colorado State
University, Fort Collins, Colorado 80523, Department of Human
Ecology, Nutritional Sciences Division, The University of Texas,
Austin, Texas 78712
APStracts 4:0052E, 1997.
A dietary copper (Cu) deficiency is associated with a 2-fold increase
in hepatic fatty acid biosynthesis. We hypothesized that the
induction of hepatic lipogenesis associated with a dietary copper
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 d a high sucrose diet that was Cu-deficient
[0.7 [mu]g Cu/g (CuD)], or -adequate [5.0 [mu]g Cu/g (CuA) ]. The CuD
diet increased FAS enzymatic activity 2-fold (P<0.05). This
rise in enzymatic activity was accompanied by a 3-fold 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 b-actin were
affected by the CuD diet. The induction of FAS gene transcription was
associated with 65-85% increase in hepatic GSH (P<0.05). When
hepatic GSH synthesis was suppressed by treating Cu-deficient rats
with L-buthionine sulfoximine, the induciton of FAS expression was
completely prevented. Similarly, feeding N-acetylcysteine to Cu
-adequate 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 upon hepatic thiol redox.
Received 27 August 1996; accepted in final form 13 February 1997.
APS Manuscript Number E422-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 5 March 1997