REGULATION OF HEPATIC DE-NOVO LIPOGENESIS IN HUMANS

The enzymatic pathway for synthesis of fatty acids from acetyl-coenzym e A, or de novo lipogenesis (DNL), is present in human liver and, to a lesser extent, in adipose tissue. Although the molecular and enzymati c regulation of the components for DNL are well characterized, the qua ntitative importance of the assembled pathway and its physiologic func tions have remained uncertain. We review methods that have been used f or measuring DNL in vivo, their limitations and the conclusions based on them. Two new methods for direct measurement of DNL in humans are d iscussed-mass isotopomer distribution analysis (MIDA) a mass spectrome tric technique based on combinatorial probabilities, and (H2O)-H-2 inc orporation. Recent findings with these methods in a variety of dietary and hormonal settings are reviewed. In particular, we focus on the qu estion of whether or not surplus carbohydrate energy is converted to f at by the liver in humans. A somewhat surprising model of the response to carbohydrate overfeeding emerges from these studies, with a number of implications for metabolic regulation in health and disease. We cl ose by speculating on potential functions of DNL in physiology and pat hophysiology if storage of surplus carbohydrate energy is not an impor tant function of DNL. The availability of techniques for quantifying D NL in vivo should make it possible to resolve these uncertainties rega rding its functions and regulation in humans.