Hepatic fatty acid synthase gene transcription is induced by a dietary copper deficiency

Am J Physiol. 1997 Jun;272(6 Pt 1):E1124-9. doi: 10.1152/ajpendo.1997.272.6.E1124.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / biosynthesis
  • Animals
  • Copper / deficiency*
  • Copper / metabolism
  • Enzyme Induction
  • Fatty Acid Synthases / biosynthesis*
  • Glutathione / metabolism
  • Iron / metabolism
  • Liver / enzymology*
  • Liver / metabolism
  • Male
  • Phosphoenolpyruvate Carboxykinase (GTP) / biosynthesis
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Transcription, Genetic*
  • Zinc / metabolism

Substances

  • Actins
  • RNA, Messenger
  • Copper
  • Iron
  • Fatty Acid Synthases
  • Phosphoenolpyruvate Carboxykinase (GTP)
  • Glutathione
  • Zinc