Mechanisms of nutritional and hormonal regulation of lipogenesis

Abstract

Fat build-up is determined by the balance between lipogenesis and lipolysis/fatty acid oxidation. In the past few years, our understanding of the nutritional, hormonal and particularly transcriptional regulation of lipogenesis has expanded greatly. Lipogenesis is stimulated by a high carbohydrate diet, whereas it is inhibited by polyunsaturated fatty acids and by fasting. These effects are partly mediated by hormones, which inhibit (growth hormone, leptin) or stimulate (insulin) lipogenesis. Recent research has established that sterol regulatory element binding protein-1 is a critical intermediate in the pro- or anti-lipogenic action of several hormones and nutrients. Another transcription factor implicated in lipogenesis is the peroxisome proliferator activated receptor gamma. Both transcription factors are attractive targets for pharmaceutical intervention of disorders such as hypertriglyceridemia and obesity.

Fig. 1. Regulation of lipogenesis in hepatocytes (left) and adipocytes (right). The effects of nutrients and hormones on the expression of lipogenic genes are mostly mediated by SREBP-1 and, in adipose tissue, by PPARγ. Lipogenesis entails a number of discrete steps, shown in the middle, which are controlled via allosteric interactions, by covalent modification and via changes in gene expression.