Tao Huang1,2, Tiange Wang2,3, Yoriko Heianza2, Dianjianyi Sun2, Kerry Ivey4, Ronen Durst5,6, Dan Schwarzfuchs7, Meir J Stampfer4,8,9, George A Bray10, Frank M Sacks4, Iris Shai11, Lu Qi2,4,9. 1. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. 2. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisana. 3. Shanghai Institute of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 4. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 5. Cardiology Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel. 6. Center for Research Prevention and Treatment of Atherosclerosis, Internal Medicine Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel. 7. The Nuclear Research Centre, Dimona, Israel. 8. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 9. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 10. Pennington Biomedical Research Center of the Louisiana State University System, Baton Rouge, Lousiana. 11. Department of Public Health, Ben Gurion University of the Negev, Beer Sheva, Israel.
Abstract
AIM: To determine whether weight-loss diets varying in macronutrients modulate the genetic effect of hepatocyte nuclear factor 1α (HNF1A) rs7957197 on weight loss and improvement of insulin resistance. MATERIALS AND METHODS: We analysed the interaction between HNF1A rs7957197 and weight-loss diets with regard to weight loss and insulin resistance improvement among 722 overweight/obese adults from a 2-year randomized weight-loss trial, the POUNDS Lost trial. The findings were replicated in another independent 2-year weight-loss trial, the Dietary Intervention Randomized Controlled Trial (DIRECT), in 280 overweight/obese adults. RESULTS: In the POUNDS Lost trial, we found that a high-fat diet significantly modified the genetic effect of HNF1A on weight loss and reduction in waist circumference (P for interaction = .006 and .005, respectively). Borderline significant interactions for fasting insulin and insulin resistance (P for interaction = .07 and .06, respectively) were observed. We replicated the results in DIRECT. Pooled results showed similar significant interactions with weight loss, waist circumference reduction, and improvement in fasting insulin and insulin resistance (P values for interaction = .001, .005, .02 and .03, respectively). Greater decreases in weight, waist circumference, fasting insulin level and insulin resistance were observed in participants with the T allele compared to those without the T allele in the high-fat diet group (P = .04, .03 and .01, respectively). CONCLUSIONS: Our replicable findings provide strong evidence that individuals with the HNF1A rs7957197 T allele might obtain more benefits in weight loss and improvement of insulin resistance by choosing a hypocaloric and high-fat diet.
RCT Entities:
AIM: To determine whether weight-loss diets varying in macronutrients modulate the genetic effect of hepatocyte nuclear factor 1α (HNF1A) rs7957197 on weight loss and improvement of insulin resistance. MATERIALS AND METHODS: We analysed the interaction between HNF1Ars7957197 and weight-loss diets with regard to weight loss and insulin resistance improvement among 722 overweight/obese adults from a 2-year randomized weight-loss trial, the POUNDS Lost trial. The findings were replicated in another independent 2-year weight-loss trial, the Dietary Intervention Randomized Controlled Trial (DIRECT), in 280 overweight/obese adults. RESULTS: In the POUNDS Lost trial, we found that a high-fat diet significantly modified the genetic effect of HNF1A on weight loss and reduction in waist circumference (P for interaction = .006 and .005, respectively). Borderline significant interactions for fasting insulin and insulin resistance (P for interaction = .07 and .06, respectively) were observed. We replicated the results in DIRECT. Pooled results showed similar significant interactions with weight loss, waist circumference reduction, and improvement in fasting insulin and insulin resistance (P values for interaction = .001, .005, .02 and .03, respectively). Greater decreases in weight, waist circumference, fasting insulin level and insulin resistance were observed in participants with the T allele compared to those without the T allele in the high-fat diet group (P = .04, .03 and .01, respectively). CONCLUSIONS: Our replicable findings provide strong evidence that individuals with the HNF1Ars7957197 T allele might obtain more benefits in weight loss and improvement of insulin resistance by choosing a hypocaloric and high-fat diet.
Authors: Su Yon Jung; Peter A Scott; Jeanette C Papp; Eric M Sobel; Matteo Pellegrini; Herbert Yu; Sihao Han; Zuo-Feng Zhang Journal: Cancer Prev Res (Phila) Date: 2020-09-14