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Papers In Press, published online ahead of print June 1, 2006
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Center for Human Nutrition, UT Southwestern Medical Center, Dallas, TX 75390-9052
Corresponding Author: Elizabeth.Parks{at}UTSouthwestern.edu
Isotopic measurement of biosynthetic rates of lipids in very low-density lipoprotein (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 are applicable to humans, have been developed - the combinatorial probability method (or mass isotopomer distribution analysis, MIDA) and 2H2O 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 VLDL-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, secretion of VLDL-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 methodologic advances.
Revised on May 31, 2006
Accepted on May 31, 2006
Recent advances in liver triacylglycerol and fatty acid metabolism using stable isotope labeling techniques
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