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Genetic determinant for amino acid metabolites and changes in body weight and insulin resistance in response to weight-loss diets: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.

ABSTRACT: Circulating branched-chain amino acids and aromatic amino acids were recently related to insulin resistance and diabetes mellitus in prospective cohorts. We tested the effects of a genetic determinant of branched-chain amino acid/aromatic amino acid ratio on changes in body weight and insulin resistance in a 2-year diet intervention trial.We genotyped the branched-chain amino acid/aromatic amino acid ratio-associated variant rs1440581 near the PPM1K gene in 734 overweight or obese adults who were assigned to 1 of 4 diets varying in macronutrient content. At 6 months, dietary fat significantly modified genetic effects on changes in weight, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) after adjustment for the confounders (all P for interaction ?0.006). Further adjustment for weight change did not appreciably change the interactions for fasting insulin and HOMA-IR. In the high-fat diet group, the C allele was related to less weight loss and smaller decreases in serum insulin and HOMA-IR (all P ? 0.02 in an additive pattern), whereas an opposite genotype effect on changes in insulin and HOMA-IR was observed in the low-fat diet group (P=0.02 and P=0.04, respectively). At 2 years, the gene-diet interactions remained significant for weight loss (P=0.008) but became null for changes in serum insulin and HOMA-IR resulting from weight regain.Individuals carrying the C allele of the branched-chain amino acid/aromatic amino acid ratio-associated variant rs1440581 may benefit less in weight loss and improvement of insulin sensitivity than those without this allele when undertaking an energy-restricted high-fat diet.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00072995.

SUBMITTER: Xu M

PROVIDER: S-EPMC3860590 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Genetic determinant for amino acid metabolites and changes in body weight and insulin resistance in response to weight-loss diets: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.

Xu Min M Qi Qibin Q Liang Jun J Bray George A GA Hu Frank B FB Sacks Frank M FM Qi Lu L

Circulation 20130227 12

<h4>Background</h4>Circulating branched-chain amino acids and aromatic amino acids were recently related to insulin resistance and diabetes mellitus in prospective cohorts. We tested the effects of a genetic determinant of branched-chain amino acid/aromatic amino acid ratio on changes in body weight and insulin resistance in a 2-year diet intervention trial.<h4>Methods and results</h4>We genotyped the branched-chain amino acid/aromatic amino acid ratio-associated variant rs1440581 near the PPM1K ...[more]

PMID: 23446828

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Project description:BackgroundThe effects of dietary composition on weight loss are incompletely understood. In addition to energy intake, fiber intake, energy density, macronutrient composition, and demographic characteristics have all been suggested to contribute to weight loss.ObjectiveThe primary aim of this analysis was to assess the role of dietary fiber as a predictor of weight loss in participants who consumed calorie-restricted diets (-750 kcal/d from estimated energy needs) for 6 mo, using data from the POUNDS Lost (Preventing Overweight Using Novel Dietary Strategies) Study-a randomized trial that examined the effects of calorie-restricted diets varying in macronutrient composition on weight loss in adults.MethodsData were randomly partitioned to a training data set (70%) in which the effects of fiber and other weight-loss predictors were identified using adjusted Least Absolute Shrinkage and Selection Operator and model averaging. The retained predictors were then fit on the testing data set to assess predictive performance.ResultsThree hundred and forty-five participants (53.9% female) provided dietary records at baseline and 6 mo. Mean ± SD age and BMI for the full sample was 52.5 ± 8.7 y and 32.6 ± 3.9 kg/m2, respectively. Mean ± SD (99% CI) weight change at 6 mo for the full sample was -7.27 ± 5.6 kg (-8.05, -6.48 kg). The final, best fit model (R2 = 0.41) included fiber, energy density, fat, age, adherence, baseline weight, race, and changes from baseline in carbohydrate, fiber, PUFA, and MUFA intake, but the most influential predictor was fiber intake ($\hat{\beta }$ = -0.37; P < 0.0001). In addition, fiber was strongly associated with adherence to the macronutrient prescriptions (P < 0.0001). Interactions between race and adherence, age, baseline weight, carbohydrate, energy density, and MUFAs were also retained in the final model.ConclusionDietary fiber intake, independently of macronutrient and caloric intake, promotes weight loss and dietary adherence in adults with overweight or obesity consuming a calorie-restricted diet. This trial was registered at clinicaltrials.gov as NCT00072995.

Project description:BackgroundObesity is closely associated with bone health. Although diet and weight loss produce many metabolic benefits, studies of weight loss diets on bone health are conflicting. Genetic variations, such as vitamin D levels, may partly account for these conflicting observations by regulating bone metabolism.ObjectiveWe investigated whether the genetic variation associated with vitamin D concentration affected changes in bone mineral density (BMD) in response to a weight-loss diet intervention.DesignIn the 2-y Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, BMD was measured for 424 participants who were randomly assigned to 1 of 4 diets varying in macronutrient intakes. A genetic risk score (GRS) was calculated based on 3 genetic variants [i.e., 7-dehydrocholesterol reductase (DHCR7) rs12785878, cytochrome P450 2R1 (CYP2R1) rs10741657 and group-specific component globulin (GC) rs2282679] related to circulating vitamin D levels. A dual-energy X-ray absorptiometry scan was performed to assess changes in whole-body BMD over 2 y. The final analysis included 370 participants at baseline.ResultsWe found a significant interaction between dietary fat intake and vitamin D GRS on 2-y changes in whole-body BMD (P-interaction = 0.02). In the high-fat diet group, participants with higher GRS showed significantly less reduction in whole-body BMD than those with lower GRS, whereas the genetic associations were not significant in the low-fat diet group. We also found a significant interaction between dietary fat intake and the GRS on 6-mo change in femur neck BMD (P-interaction = 0.02); however, the interaction became nonsignificant at 2 y.ConclusionOur data indicate that dietary fat intake may modify the effect of vitamin D-related genetic variation on changes in BMD. Overweight or obese patients predisposed to sufficient vitamin D may benefit more in maintaining BMD along with weight loss by eating a low-fat diet. This trial was registered at clinicaltrials.gov as NCT03258203.

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Project description:The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown.To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight loss setting.Data analysis was conducted among 569 overweight and obese participants aged 30-70 years with normal thyroid function participating in the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine (T3), free thyroxine (T4), total T3, total T4 and thyroid-stimulating hormone (TSH)), anthropometric measurements and biochemical parameters were assessed at baseline, 6 months and 24 months.Participants lost an average of 6.6?kg of body weight during the first 6 months and subsequently regained an average of 2.7?kg of body weight over the remaining period from 6 to 24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss±s.e. was -3.87±0.9 vs -5.39±0.9?kg for free T3 (Ptrend=0.02) and -4.09±0.9 vs -5.88±0.9?kg for free T4 (Ptrend=0.004). The thyroid hormones did not predict weight regain in 6-24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides and leptin at 6 months and 24 months (all P<0.05).In this diet-induced weight loss setting, higher baseline free T3 and free T4 predicted more weight loss, but not weight regain among overweight and obese adults with normal thyroid function. These findings reveal a novel role of thyroid hormones in body weight regulation and may help identify individuals more responsive to weight loss diets.

Dataset Information

Genetic determinant for amino acid metabolites and changes in body weight and insulin resistance in response to weight-loss diets: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.

Publications

Genetic determinant for amino acid metabolites and changes in body weight and insulin resistance in response to weight-loss diets: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.

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