Hyperlipidemias: Roberts R

Roberts R. · University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y 4W7, Canada. · Curr Atheroscler Rep. · Pubmed #18489845 No free full text.

Abstract: Common multigene disorders account for 80% of deaths in the world and all have significant genetic predisposition. Coronary artery disease and myocardial infarction (MI) account for more than 40% of these deaths. The genetic component is due to multiple genes, each contributing only minimally to the phenotype. Linkage analysis, which has been successful in identifying rare disorders that cause MI, is not sensitive for multigene disorders. The recent candidate case-control approach has been equally unsuccessful. Multigene disorders require genome-wide association studies involving genotyping hundreds of thousands of DNA markers in thousands of individuals with replication in independent populations. Platforms with 500,000 and 1 million single nucleotide polymorphisms provide the necessary high-throughput genotyping for genome-wide association. The first confirmed common locus, 9p21, is independent of conventional risk factors. Identifying the 9p21 gene will elucidate novel mechanisms responsible for MI. Comprehensive prevention of MI based on individual genetic variants (personalized medicine) is expected in the next decade.

Roberts R, Bickerton AS, Fielding BA, Blaak EE, Wagenmakers AJ, Chong MF, Gilbert M, Karpe F, Frayn KN. · Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom. · Am J Clin Nutr. · Pubmed #18400703 links to  free full text

Abstract: BACKGROUND: Short-term high-carbohydrate (HC) diets induce metabolic alterations, including hypertriacylglycerolemia, in both the fasting and postprandial states. The underlying tissue-specific alterations in fatty acid metabolism are not well understood. OBJECTIVE: We investigated alterations in exogenous and endogenous fatty acid metabolism by using stable isotope tracers to label meal triacylglycerol and plasma fatty acids. DESIGN: Eight healthy subjects consumed isocaloric diets containing a high percentage of energy from carbohydrates or a higher percentage of energy from fat for 3 d in a randomized crossover dietary intervention study. A test meal containing [U-13C] palmitate was combined with intravenous infusion of [2H2] palmitate to label plasma fatty acids and VLDL triacylglycerol. Blood and breath samples were taken before the meal and for 6 h postprandially. Blood samples were drawn from the femoral artery and from veins draining subcutaneous adipose tissue and forearm muscle for monitoring of tissue-specific metabolic substrate partitioning. RESULTS: Systemic triacylglycerol concentrations were increased in both fasting (P = 0.02) and postprandial (P = 0.02) periods, and a greater amount of infused labeled fatty acid appeared in VLDL triacylglycerol after the HC diet than after the higher-fat diet (P = 0.05). Significantly less 13CO2 was exhaled after the HC diet (P = 0.04) and significantly less production of 13CO2 was seen across forearm muscle (P = 0.04). Systemic 3-hydroxybutyrate was significantly lower, postprandially, after the HC diet (P = 0.02). CONCLUSION: Metabolic alterations suggestive of repartitioning of fatty acids away from oxidation toward esterification in both liver and muscle occur in response to short-term adaptation to a HC diet.