The age-related differences in obese and fatty acid synthase gene expression in white adipose tissue of rat

To determine if the age-dependent increase of adiposity is directly related to altered obese (ob) and fatty acid synthase (FAS) gene expression, we as sessed an adiposity index, leptin and FAS mRNA levels, FAS activity in peri renal adipose tissue and serum leptin concentration in rats aged 1, 2, 3, 6 and 20 months. The results indicate that there are two distinct phases of changes in perirenal white adipose tissue leptin mRNA level and serum lepti n concentration. The first phase, between I and 3 months of the animals' li ves, was characterized by a strong positive correlation between adiposity i ndex and leptin mRNA level as well as serum leptin concentration. In the se cond phase (over 3 months) no significant changes of leptin mRNA and serum concentration occurred. A close correlation between the age-induced increas e of leptin mRNA abundance and serum leptin concentration and the age-induc ed suppression of FAS gene expression in the same tissue was observed. This suggests that the changes of FAS gene expression occur in response to seru m leptin concentration and that in mature rats the high level of ob gene ex pression and consequently the high leptin concentration protect the white a dipose tissue cells against fat overload by two independent mechanisms: (a) preventing an increase of food intake through the leptin action on the hyp othalamus; (b) inhibiting FAS gene expression and consequently decreasing t he rate of lipogenesis. (C) 2001 Elsevier Science B.V. All rights reserved.