EXERCISE TRAINING DOWN-REGULATES OB GENE-EXPRESSION IN THE GENETICALLY-OBESE SHHF MCC-FA(CP) RAT/

The recently cloned obesity gene (ob) encodes a protein, leptin, which is secreted from adipose tissue and interacts with hypothalamic recep tors to decrease appetite, increase energy expenditure, and reduce bod y lipid stores. The levels of ob mRNA are increased in several models of obesity, consistent with the hypothesis that obese animals may be r esistant to the actions of leptin. The present study examined the impa ct of increased energy expenditure through exercise training on ob mRN A gene expression and body composition in the SHHFIMc-fa(cp) male rat, a rodent model of obesity, insulin resistance, and type II diabetes. Six week old lean and obese animals were trained 8-12 weeks by treadmi ll running at 70 % peak oxygen uptake, 5 dayslwk, for 1.5 hr/day. Afte r endurance training, exercised rats had significantly lower total bod y fat compared to sedentary rats of the same age, despite maintaining the same body weight. In the obese SHHF/Mcc-fa(cp) rat, the level of o b mRNA expression was markedly increased by four fold in subcutaneous adipose tissue compared to lean controls (p<0.05). In response to exer cise training, there was a significant 85 % decrease in ob mRNA in exe rcised-training lean rats (p<0.05) compared with non-exercised control s, while in obese-exercised rats, ob gene expression was significantly reduced only by 50 % relative to non-exercised obese rats (p<0.05). T hese results demonstrate that exercise training reduces fat mass and o b mRNA in lean and obese rats, and supports the hypothesis of a feedba ck loop between the adipocyte and hypothalamus that attempts to mainta in body weight at a constant level by reducing ob gene expression in r esponse to increased energy expenditure.