A B S T R A C TObjectives: High-fat high-sucrose diet (HFHS) overfeeding is one of the main factors responsible for the increased prevalence of metabolic disorders. Elevated levels of branched-chain amino acids (BCAAs) have been associated with metabolic dysfunctions, including insulin resistance (IR). The aim of this study was to elucidate whether elevated BCAA levels are the cause or the consequence of IR and to determine the mechanisms and tissues involved in such a phenotype. Methods: We performed a 2-mo follow-up on minipigs overfed an HFHS diet and focused on kinetics fasting and postprandial (PP) BCAA levels and BCAA catabolism in key tissues. Results: The study of the fasting BCAA elevation reveals that BCAA accumulation in the plasma compartment is well correlated with IR markers and body weight. Furthermore, the PP excursion of BCAA levels after the last HFHS meal was exacerbated when compared with that of the first meal, suggesting a reduced amino acid oxidation potential. Although only minor changes in BCAA metabolism were observed in liver, muscle, and the visceral adipose tissue, the oxidative deamination potential of the subcutaneous adipose tissue was blunted after 60 d of HFHS feeding. Conclusions: To our knowledge, the present results demonstrated for the first time in a swine model of obesity and IR, the existence of a phenotype related to high-circulating BCAA levels and metabolic dysregulation. The oxidative BCAA capacity reduction specifically in the subcutaneous adipose tissue emerges, at least in the present swine model, as the more plausible metabolic explanation for the elevated blood BCAA phenotype.© 2017 Elsevier Inc. All rights reserved. IntroductionThe consumption of high-energy diets rich in fat, sugars, or both is increasing worldwide, paralleling the increases in obesity and metabolic diseases like type 2 diabetes mellitus and cardiovascular diseases [1]. High-fat high-sugar (HFHS) diets are highly palatable and have a poorly controlled intake [2]. Despite the high interindividual variability in the sensitivity to weight and adiposity gains, HFHS overfeeding is one of the main factors responsible for the increased prevalence of adiposity and metabolic disorders involving insulin resistance (IR) and leading to chronic metabolic diseases [3].Among the most recently studied metabolic dysfunctions and plasma metabolites alterations associated with IR occurrence, the place of branched-chain amino acids (BCAA) is questioned [4]. An increased level of plasma BCAA is observed in individuals who are insulin resistant and shown to be altered simultaneously with IR and diabetes installation [5]. To date, the underlying mechanisms explaining these increased BCAA levels is still under debate [6,7] and whether the increased level of BCAA should be considered as causal of IR or a consequence of its installation remains controversial [7]. Indeed, a BCAA-altered metabolism in adipose tissue (AT) associated with a reduction of the capacity of the BCAA catabolic enzymes has been clearly shown in ca...

Elevated plasma branched-chain amino acids (BCAA) levels are often observed in obese insulin-resistant (IR) subjects and laboratory animals. A reduced capacity of the adipose tissues (AT) to catabolize BCAA has been proposed as an explanation, but it seems restricted to obesity models of genetically modified or high fat–fed rodents. We aimed to determine if plasma BCAA levels were increased in a model of IR without obesity and to explore the underlying mechanisms. Rats were fed with a standard diet, containing either starch or fructose. BCAA levels, body weight and composition were recorded before and after 5, 12, 30, or 45 days of feeding. Elevated blood BCAA levels were observed in our IR model with unaltered body weight and composition. No changes were observed in the liver or the AT, but instead an impaired capacity of the skeletal muscle to catabolize BCAA was observed, including reduced capacity for transamination and oxidative deamination. Although the elevated blood BCAA levels in the fructose-fed rat seem to be a common feature of the IR phenotype observed in obese subjects and high fat–fed animals, the mechanisms involved in such a metabolic phenomenon are different, likely involving the skeletal muscle BCAA metabolism.

With aging, skeletal muscle becomes resistant to the anabolic effect of dietary proteins and sarcopenia develops.