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Background The practical relevance of metabolic adaptation remains a controversial issue. To the best of our knowledge, no study has properly evaluated the role of metabolic adaptation in modulating weight loss outcomes. Therefore, the aim of this study was to determine the association between metabolic adaptation, at the level of resting metabolic rate (RMR), and weight and fat mass (FM) loss after low-energy diets (LED), after adjusting for dietary adherence and other confounders. Methods 71 individuals with obesity (BMI: 34.6 ± 3.4 kg/m2; age: 45.4 ± 8.2 years; 33 males) were randomized to one of three 1000 kcal/day diets for 8 weeks. Body weight, FM and fat-free mass (FFM) (air displacement plethysmography), RMR (indirect calorimetry) and physical activity level (PAL) (armbands) were measured at baseline and at week 9. Metabolic adaptation at week 9 was defined as measured RMR minus predicted RMR at week 9. An equation to predict RMR was derived from baseline data of all participants that were part of this analysis and included age, sex, FM and FFM as predictors. Dietary adherence was calculated from RMR, PAL and body composition changes. Linear regression was used to assess the potential role of metabolic adaptation in predicting weight and FM loss after adjusting for dietary adherence, average PAL, sex, baseline FM and FFM and randomization group. Results Participants lost on average 14 ± 4 kg of body weight (13 ± 3%) and presented with metabolic adaptation (−92 ± 110 kcal/day, P P P 2 = 0.88, 0.93, respectively, P Conclusion In individuals with obesity, metabolic adaptation at the level of RMR is associated with less weight and FM loss in response to LED. Trial registration ID: NCT02944253.

Background The prevalence of type 2 diabetes is higher among African Americans (AA) vs European Americans (EA), independent of obesity and other known confounders. Although the reason for this disparity is not known, it is possible that relatively low levels of vitamin D among AA may contribute, as vitamin D has been positively associated with insulin sensitivity in some studies. The objective of this study was to test the hypothesis that dietary vitamin D would be associated with a robust measure of insulin sensitivity in AA and EA women. Methods Subjects were 115 African American (AA) and 137 European American (EA) healthy, premenopausal women. Dietary intake was determined with 4-day food records; the insulin sensitivity index (SI) with a frequently-sampled intravenous glucose tolerance test and minimal modeling; the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) with fasting insulin and glucose; and body composition with dual-energy X-ray absorptiometry. Results Vitamin D intake was positively associated with SI (standardized β = 0.18, P = 0.05) and inversely associated with HOMA-IR (standardized β = -0.26, P = 0.007) in AA, and the relationships were independent of age, total body fat, energy intake, and % kcal from fat. Vitamin D intake was not significantly associated with indices of insulin sensitivity/resistance in EA (standardized β = 0.03, P = 0.74 and standardized β = 0.02, P = 0.85 for SI and HOMA-IR, respectively). Similar to vitamin D, dietary calcium was associated with SI and HOMA-IR among AA but not EA. Conclusions This study provides novel findings that dietary vitamin D and calcium were independently associated with insulin sensitivity in AA, but not EA. Promotion of these nutrients in the diet may reduce health disparities in type 2 diabetes risk among AA, although longitudinal and intervention studies are required.

Background The objective of the present study was to map candidate loci influencing naturally occurring variation in triacylglycerol (TAG) storage using quantitative complementation procedures in Drosophila melanogaster. Based on our results from Drosophila, we performed a human population-based association study to investigate the effect of natural variation in LAMA5 gene on body composition in humans. Results We identified four candidate genes that contributed to differences in TAG storage between two strains of D. melanogaster, including Laminin A (LanA), which is a member of the α subfamily of laminin chains. We confirmed the effects of this gene using a viable LanA mutant and showed that female flies homozygous for the mutation had significantly lower TAG storage, body weight, and total protein content than control flies. Drosophila LanA is closely related to human LAMA5 gene, which maps to the well-replicated obesity-linkage region on chromosome 20q13.2-q13.3. We tested for association between three common single nucleotide polymorphisms (SNPs) in the human LAMA5 gene and variation in body composition and lipid profile traits in a cohort of unrelated women of European American (EA) and African American (AA) descent. In both ethnic groups, we found that SNP rs659822 was associated with weight (EA: P = 0.008; AA: P = 0.05) and lean mass (EA: P= 0.003; AA: P = 0.03). We also found this SNP to be associated with height (P = 0.01), total fat mass (P = 0.01), and HDL-cholesterol (P = 0.003) but only in EA women. Finally, significant associations of SNP rs944895 with serum TAG levels (P = 0.02) and HDL-cholesterol (P = 0.03) were observed in AA women. Conclusion Our results suggest an evolutionarily conserved role of a member of the laminin gene family in contributing to variation in weight and body composition.