Differential regulation of hepatic gene expression by starvation versus refeeding following a high-sucrose or high-fat diet.

Objectives: The objective of this work was to determine the effects of starvation versus refeeding following a high-sucrose diet (HS) or high-fat diet (HF) on fatty acid metabolism in mice.

Methods: The mice were fed an AIN-76 control diet (CD), a modified HS, or an HF. The three dietary groups were subdivided into three groups each: those fed experimental diets for 12 wk, mice starved for 48 h after 12 wk on an experimental diet, and those with the same starvation treatment but with 72 h of refeeding after starvation, respectively.

Results: Serum total cholesterol levels of CD and HF groups decreased and then increased under starvation and refeeding states, respectively. Refeeding HS and HF increased serum levels of low-density lipoprotein (LDL) cholesterol compared with refeeding of the CD group. Starvation significantly increased hepatic levels of total cholesterol in the HS and HF groups compared with the CD group. Hepatic acyl coenzyme A (CoA) synthetase (ACS) levels in the CD and HS groups but not the HF group increased and then decreased under starved and refed states, respectively; an opposite regulation was observed in the HF group. Levels of hepatic acetyl-CoA carboxylase (ACC) in the HS and HF groups were significantly increased by refeeding. Hepatic levels of carnitine palmitoyltransferase-I mRNA were significantly enhanced by starvation and refeeding in the HS group but decreased in CD and then increased in the HF group.

Conclusions: Changes in dietary energy nutrients, fasting, and refeeding affect hepatic ACS, CPT-I, and ACC mRNA expression, and these results will serve to enhance our understanding of the molecular mechanisms underlying regulation of fatty acid metabolism.