Present and future studies on lipogenesis in animals and human subjects

Lipogenesis occurs in all vertebrate species and has a critical role in ene rgy balance, providing a means whereby excess energy can be stored as a fat . The metabolic pathways involved and their tissue distribution in differen t species, including man, are well known. The responses of lipogenesis to d iet and to physiological and pathological states have been the subject of m any studies. At a molecular level the major rate-controlling enzymes have b een identified and their acute, and to a lesser extent chronic, control by hormones have been investigated extensively. However, there is no reason to suppose that all factors regarding lipogenesis have been identified (e.g. the recent discovery of acylation-stimulating protein). Little is known abo ut the movement of newly-synthesized triacylglycerols in cells, either for secretion or storage. The production of leptin and tumour necrosis factor a by adipocytes provides a novel means of feedback control of triacylglycero l production, leptin by decreasing appetite and tumour necrosis factor a by inducing insulin resistance. The synthesis of these peptides appears to va ry with the amount of triacylglycerol in adipocytes, but the molecular basi s of this process is unknown. Elucidation of the signalling systems involve d in the acute and chronic regulation of lipogenesis is also important, bot h with respect to some homeorhetic adaptations and also in some pathologica l conditions (e.g. non-insulin-dependent diabetes). Finally, molecular biol ogy is revealing unexpected complexities, such as multiple promoters and di fferent isoforms of enzymes (e.g. acetyl-CoA carboxylase; EC 6.4.1.2) exhib iting tissue specificity. Molecular biology, through transgenesis, also off ers novel and powerful means of manipulating lipogenesis.