Recent advances in liver triacylglycerol and fatty acid metabolism using stable isotope labeling techniques

Isotopic measurement of biosynthetic rates of lipids in VLDL particles has long posed difficult technical problems. In this review, key methodologic issues and recent technical advances are discussed. A common problem for all biosynthetic measurements is the requirement to measure isotopic labeling of the true intracellular biosynthetic precursor pool. Two techniques that address this problem for lipid biosynthesis, and that are applicable to humans, have been developed-the combinatorial probability method (or mass isotopomer distribution analysis) and (H2O)-H-2 incorporation. The theoretical basis and practical application of these methods, both of which involve mass spectrometry, are described. Issues relevant to specific lipid components of VLDL, such as differences in the labeling of the various particle lipids (phospholipid, cholesterol, etc.), and the contribution of an intrahepatic cytosolic triacylglycerol (TG) storage pool to VLDI-TG are discussed. In summary, advances in stable isotope-mass spectrometric techniques now permit accurate measurement of liver-TG synthesis and flux. In vivo regulation of the synthesis, assembly, and secretion of VLDI-TG in humans is thereby accessible to direct investigation. Patient-oriented research in conditions such as dyslipidemia and hepatic steatosis is made feasible by these scientific advances.