TRACING LIPOGENESIS IN HUMANS USING DEUTERATED WATER

Determination of quantitative de novo fat synthesis rates is important in our understanding of the role of nutritional factors in macronutie nt utilization and obesity development. To address these questions, we developed and applied a method for measuring lipogenesis using the up take of deuterium from heavy water into triglyceride fatty acids (TGFA ) in humans. Our model examined the plateau of deuterium enrichment in plasma very light density lipoprotein (VLDL) TGFA relative to the max imum as indicative of the fraction of VLDL-TGFA synthesized. Plateau e nrichment was observed after 12 h of prime-constant oral deuterium oxi de administration. Our initial studies applied this model in healthy h umans consuming typical diets to demonstrate rates of TGFA synthesis a mounting to 2 g . day(-1). In subsequent experiments it was shown that this level of synthesis was not affected by the frequency with which daily meals were consumed. Furthermore, in a clinical application, our results using this approach demonstrated that compared with normolipi demic controls, individuals with type III hyperlipoproteinemia display ed elevated TGFA but normal cholesterol synthesis rates. In summary, c ompared with other available methods for determination of lipogenesis, deuterium uptake is safe, direct, and inexpensive. Results suggest th at under most dietary circumstances, human de novo lipogenesis is mino r, thus dietary fat and carbohydrate balances remain largely independe nt.