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


CONCLUSIONS
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.
Fiebig
Russell G
RG
Interdepartmental Graduate Program in Nutritional Science, and Department of Kinesiology, University of Wisconsin-Madison, Madison, WI, USA.
Hollander
John M
JM
Ney
Denise
D
Boileau
Richard
R
Jeffery
Elizabeth
E
Ji
Li  Li
L
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D001823:Body Composition; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D064429:Fatty Acid Synthases / Q000378:metabolism*; D015870:Gene Expression; D008099:Liver / Q000378:metabolism*; D009765:Obesity / Q000503:physiopathology*; D009929:Organ Size; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker
D012333:RNA, Messenger; D064429:Fatty Acid Synthases