Exercise attenuates nuclear protein binding to gene regulatory sequences of hepatic fatty acid synthase

The effect of an acute bout of exhaustive exercise on hepatic fatty acid sy nthase (FAS) gene expression was examined in rats. Female Sprague-Dawley ra ts (age 8 wk) were fasted for 48 h (F, n = 6), or fasted, refed a high-fruc tose diet for 6 h, and killed at rest (R, n = 6) or killed after running on a treadmill at 27 m/min and 5% grade for 88 +/- 7 min (E, n = 6). Gel mobi lity shift assay indicated that R rats had twofold higher liver nuclear pro tein binding to oligonucleotides corresponding to the insulin responsive se quence (-71/-50) and carbohydrate response element (+283/+303) on the FAS p romoter, compared with F rats. Exercise severely attenuated this binding in liver nuclear extracts to the levels seen in F rats. Competition and super shift experiments revealed that the bound protein complexes contained the u pstream stimulatory factors. Nuclear run-on experiment revealed a 49-fold i ncrease in transcription rate of the FAS gene in R vs. F rats, whereas exer cise suppressed the transcription rate. FAS mRNA abundance and FAS enzyme a ctivity were dramatically increased with refeeding but were unaltered by ex ercise. The results reveal that dietary induction of hepatic FAS is stimula ted by increased nuclear protein binding to insulin responsive sequence and carbohydrate response element, whereas exhaustive exercise attenuates the binding, which may precede downregulation of FAS mRNA and enzyme synthesis reported in our previous work (M. A. Griffiths, R. Fiebig, M. T. Gore, D. H . Baker, K. Esser, L. Oscai, and L. L. Ji. J. Nutr. 126, 1959-1971, 1996).