Objective To measure long-term changes in resting metabolic rate (RMR) and body composition in participants of The Biggest Loser competition. Methods Body composition was measured by dual energy X-ray absorptiometry and RMR was determined by indirect calorimetry at baseline, at the end of the 30 week competition, and 6 years later. Metabolic adaptation was defined as the residual RMR after adjusting for changes in body composition and age. Results Of the 16 Biggest Loser competitors originally investigated, 14 participated in this follow-up study. Weight loss at the end of the competition was (mean±SD) 58.3±24.9 kg (p<0.0001) and RMR decreased by 610±483 kcal/d (p=0.0004). After 6 years, 41.0±31.3 kg of the lost weight was regained (p=0.0002) while RMR was 704±427 kcal/d below baseline (p<0.0001) and metabolic adaptation was −499±207 kcal/d (p<0.0001). Weight regain was not significantly correlated with metabolic adaptation at the competition’s end (r=−0.1, p=0.75) but those subjects maintaining greater weight loss at 6 years also experienced greater concurrent metabolic slowing (r=0.59, p=0.025). Conclusions Metabolic adaptation persists over time and is likely a proportional, but incomplete, response to contemporaneous efforts to reduce body weight.

Summary Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5 day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53±6 g/d of body fat, fat oxidation was unchanged by fat restriction leading to 89±6 g/d of fat loss and was significantly greater than carbohydrate restriction (p=0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with isocaloric diets varying in carbohydrate and fat.

Background MicroRNAs (miRNAs) are non-coding RNA molecules that play important roles in the pathogenesis of various kidney diseases. We investigated whether patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) have distinct circulating and urinary miRNA expression profiles that could lead to potential development of noninvasive biomarkers of the disease. Materials and methods Exosome miRNAs were extracted from plasma and urine samples of patients with primary FSGS (n=16) or MCD (n=5) and healthy controls (n=5). Differences in miRNA abundance were examined using Affymetrix GeneChip miRNA 3.0 arrays. QRT-PCR was used to validate the findings from the array. Results Comparison analysis of FSGS versus MCD revealed 126 and 155 differentially expressed miRNAs in plasma and in urine, respectively. Only 38 of these miRNAs were previously cited, whereas the remaining miRNAs have not been described. Comparison analysis showed that a significant number of miRNAs were down-regulated in both plasma and urine samples of FSGS patients compared to those with MCD. Plasma levels of miR-30b, miR-30c, miR-34b, miR-34c, and miR-342, and urine levels of mir-1225-5p were up-regulated in MCD patients compared to FSGS patients and controls (p<0.001). Urinary levels of mir-1915 and miR-663 were down-regulated in FSGS patients compared to MCD and controls (p<0.001), whereas the urinary levels of miR-155 were up-regulated in FSGS patients when compared to MCD patients and controls (p<0.005). Conclusions Patients with FSGS and MCD have a unique circulating and urinary miRNA profile. The diagnostic and prognostic potential of miRNAs in FSGS and MCD warrants further studies.