| Physiologically adaptive gain in body mass, such as that which occurs prior to hibernation in seasonal breeding mammals, has been postulated to result from hypothalamic resistance to the anorexigenic effects of leptin. Similarly, the pathophysiological increase in body mass that occurs with diet-induced obesity is also a state of hypothalamic leptin resistance. I investigated mechanisms of development of obesity in wild-type and leptin-deficient mice and the mechanisms of adaptive increases in body mass during the premigration/prehibernation period in the little brown myotis, Myotis lucifugus. I hypothesized that similar molecular mechanisms might account, in part, for both types of mass gain in mammals, and that these mechanisms would include changes in expression of genes related to leptin signal transduction. Mass gain in wild-type mice occurred beginning 12 days after mice were placed on a high fat diet (HFD). Interestingly, the increase in body mass occurred without an increase in energy consumption. These effects were due largely to the saturated fat component of the HFD. Increase in body mass in mice resulted in hyperleptinemia, hyperinsulinemia and hyperglycemia. Expressions of genes related to metabolism and leptin signal transduction, specifically the STAT3 pathway, were altered in a tissue- and time-dependent manner during 15 weeks of HFD. In leptin-deficient ob/ob mice, HFD resulted in an increase in body mass with or without leptin-replacement. As in wild-type mice, increase in body mass on HFD in ob/ob mice was accompanied by changes in hypothalamic, hepatic, and adipose tissue mRNA levels of genes related to intracellular metabolism and leptin signaling. Similar changes in some but not all of these genes were observed in Myotis lucifugus during the premigration/prehibernation period, although the expected seasonal increase in body mass was not accompanied by hyperleptinemia. In conclusion, diets high in saturated fats lead to increases in body mass without an increase in energy consumption, possibly through changes in hypothalamic, hepatic and adipose tissue expression of genes associated with metabolism and leptin signaling. The expressions of certain genes are altered in both adaptive and maladaptive gains in body mass, although the mechanisms in each case appear to be different. |
