Long-term dietary interventions, amino acid metabolites, genetics, and glycemic control

Summary of the science reportApplication 2011036Long-term dietary interventions, amino acid metabolites, genetics, and glycemic control; the POUNDS LOST / DIRECT collaborationDr. Shai Iris Ben Gurion University , Epidemiology, Beer Sheva, Israel.

Dr. Qi Lu Harvard School of Public Health , Department of Nutrition, Boston, MA, USA.Dr. Durst Ronen Hadassah Medical Organization, Cardiology, Jerusalem, Israel.Dr. Sacks Frank Harvard Medical School, Department of Nutrition , Boston, MA, USA.Dr. Stampfer Meir J Harvard Medical School, Channing Lab, PH School, Boston, MA, USA.Dr. Schwarzfuchs Dan Nuclear Research Center - Negev, medical department, Beer Sheva, Israel.

We have conducted the POUND-LOST/DIRECT collaboration between two state-of-the-art independent 2-year weight-loss RCTs that compared different diets: The POUNDS-LOST and the DIRECT trials. This enabled us to leverage these trials data to address several specific aims.

Circulating amino acids, such as branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), are associated with diabetes risk; however, it is unclear how a long-term dietary intervention for weight-loss affects circulating AA. We examined the effects of weight-loss diets on long-term changes in plasma AA and the associations of these changes with weight loss and the improvement of insulin resistance. We repeatedly measured plasma AA profiles over 2y in overweight/obese participants (POUNDS-LOST: n=774, DIRECT: n=318). In both trials, weight loss was directly related to the concurrent reduction of the BCAAs leucine and isoleucine, the AAAs tyrosine and phenylalanine, and 4 other AA. Additionally, reductions in alanine and tyrosine were significantly related to improved insulin resistance, independent of weight loss (both P

Little is known about whether cholesteryl-ester-transfer-protein (CETP) genetic variation may modify the effect of weight-loss diets varying in fat content on changes in lipid levels. We analyzed the interaction between the CETP variant rs3764261 and dietary interventions on changes in lipid levels among 732 adults from the POUNDS-LOST and replicated the findings in DIRECT cohort (n=171). Our study provides replicable evidence that individuals with CETP rs3764261(CC) genotype might derive greater effects on raising HDL-c and lowering triglycerides by choosing a low-carbohydrate/high-fat weight-loss diet instead of a low-fat diet (J Lipid Res).