SYNTHESIS OF FAT IN RESPONSE TO ALTERATIONS IN DIET - INSIGHTS FROM NEW STABLE-ISOTOPE METHODOLOGIES

Synthesis of fatty acids, or de novo lipogenesis (DNL), is an intensiv ely researched metabolic pathway whose functional significance and met abolic role have nevertheless remained uncertain. Methodologic problem s that limited previous investigations of DNL in vivo and recent metho dologic advances that address these problems are discussed here. In pa rticular, deuterated water incorporation and mass isotopomer distribut ion analysis techniques are described. Recent experimental results in humans based on these techniques are reviewed, emphasizing dietary and hormonal factors that modulate DNL and quantitative significance of D NL under various conditions, including carbohydrate overfeeding. The s omewhat surprising finding that DNL appears not to be a quantitatively major pathway even under conditions of surplus carbohydrate energy in take, at least in normal adults on typical Western diets, is discussed in depth. Nutritional and metabolic implications of these results are also noted, and some speculations on possible functional roles of DNL in normal physiology and disease states are presented in this context . In summary, methodologic advances have added to our understanding of DNL and its regulation, but many questions concerning quantitation an d function remain unanswered.