Leptin and age-related down-regulation of lipogenic enzymes genes expression in rat white adipose tissue

The age-related inverse relationship between gene expression of lipogenic enzymes and leptin gene expression as well as inhibitory effect of leptin on lipogenic enzyme's gene expression suggest that leptin could be responsible in part for the low rate of lipogenesis in white adipose (WAT) of old rats. Based on the data published recently we propose a model for the direct inhibitory effect of leptin on lipogenesis. This model may explain the age-related decrease of lipogenic activity in WAT. It is likely that despite of higher concentration of noradrenaline (which inhibits leptin gene expression in WAT) in old animals, the age-dependent decrease of beta-adrenergic receptor density in rat adipocytes may lead to the increase of leptin gene expression and to the increase of WAT leptin concentration. High concentration of leptin in adipose tissue decreases sterol regulatory element binding protein-1 (SREBP-1) gene expression by paracrine and/or autocrine action on adipocyte, which leads to the decrease of SREBP-1c level (mature form). The suppression of SREBP-1c synthesis causes a decrease of lipogenic enzyme's gene expression which consequently results in lower rate of fatty acid synthesis in WAT. This model does not exclude the indirect, via hypothalamus (by decreasing food consumption), inhibitory action of leptin on WAT lipogenesis. Therefore, it is likely that leptin exerts its inhibitory effect on WAT lipogenesis both directly at the level of adipocytes, and indirectly through hypothalamus by decreasing food intake. The inhibitory effect of of high leptin concentration on lipogenesis in WAT of old rats could prevent over-accumulation of triacylglycerols in adipocyte, and by this way could protect against further development of the fat mass.