Training down-regulates fatty acid synthase and body fat in obese Zucker rats


Medicine & Science in Sports & Exercise: July 2002 - Volume 34 - Issue 7 - pp 1106-1114
BASIC SCIENCES: Original Investigations

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.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

©2002The American College of Sports Medicine