Leptin decreases lipogenic enzyme gene expression through modification of SREBP-1c gene expression in white adipose tissue of aging rats.

Aging is associated with a significant reduction of lipogenic enzyme gene expression and lipogenesis in white adipose tissue (WAT). The age-related increase of lep gene expression could be, in part, responsible for these changes. Considering that sterol regulatory element binding protein 1c (SREBP-1c) plays an important role in regulation of lipogenic enzyme gene expression, it is likely that the age-related decrease of WAT lipogenic potential could be a consequence of the inhibition of SREBP-1c gene expression by leptin. We determined whether the increase of lep gene expression would account for the age-related decrease in SREBP-1c and its direct target, main lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), by assaying the messenger RNA (mRNA) levels of SREBP-1c, FAS, ACC, and leptin in WAT of 2-month-old (young) and 20-month-old (old) rats. Leptin mRNA level was much higher in the old animals, whereas in contrast, old rats displayed much lower mRNA levels of SREBP-1c and lipogenic enzymes. Moreover, experimentally increased plasma leptin concentration in young rats to the value observed in old rats resulted in the decrease of SREBP-1c, FAS, and ACC mRNA levels in WAT. Thus, the increase of lep gene expression could, in part, account for the reduced SREBP-1c gene expression and, consequently, the diminished lipogenic activity in WAT of old animals.