FIEBIG, R. G., J. M. HOLLANDER, D. NEY, R. BOILEAU, E. JEFFERY, and L. L. JI. Training down-regulates fatty acid synthase and body fat in obese Zucker rats. Med. Sci. Sports Exerc., Vol. 34, No. 7, pp. 1106–1114, 2002.
The purpose of this study was to investigate whether chronic exercise training attenuates fatty acid synthase, the rate-limiting enzyme for hepatic lipogenesis, and the accumulation of body fat by using obese Zucker rats (OZR) as a model.
Female obese Zucker (fa/fa) rats (O, N = 16) and their lean litter mates (L, N = 16) were randomly divided into a trained (T) and untrained (U) group. T was performed on a treadmill for 2 h·d−1, 5 d·wk−1, 10 wk with running speed and grade adjusted to elicit similar workloads. All rats were meal-fed a high-cornstarch diet for 4 h·d−1 and killed 8 h after the initiation of the last meal and 27 h after the last T session, in the resting state.
O rats exhibited twofold higher FAS activity and sixfold higher FAS mRNA abundance in the liver than L rats (P < 0.05), accompanied by a severe hyperinsulinemia (P < 0.05) but normal glucagon and glucose levels. FAS activity, but not mRNA level, was decreased by 18% with T in O rats (P < 0.05). T decreased percent body fat in both O and L rats (P < 0.05), and increased lean body mass in O rats (P < 0.05). Hepatic fatty acid profile showed higher 16:0, 16:1, and 18:1 concentrations in O rats, whereas 18:0, 18:2, and 20:4 were lower (P < 0.05). Training increased 20:4 in both O and L rats (P < 0.08). Nuclear protein binding to the insulin response sequence (IRS/A) and carbohydrate response element (ChoRE) on FAS gene promoter was decreased, whereas inverted CAATT box element (ICE) binding was increased in O versus L rats (P < 0.05). Training did not affect the binding of these gene sequences.
De novo lipogenesis was greatly enhanced in OZR. Endurance training decreased body fat, which is partly explained by a decreased FAS activity. However, FAS down-regulation was not due to altered nuclear protein binding to FAS gene.
Interdepartmental Graduate Program in Nutritional Science, and Department of Kinesiology, University of Wisconsin-Madison, Madison, WI; and Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Champaign, IL
Submitted for publication August 2001.
Accepted for publication February 2002.