Time-course changes in circulating branched-chain amino acid levels and metabolism in obese Yucatan minipig

Objectives: High fat-high sucrose diet (HFHS) over-feeding is one of the main factors responsible for the increased prevalence of metabolic disorders. Elevated branched chain amino acids (BCAA) levels have been associated with metabolic dysfunctions, including insulin resistance (IR). The aim of our study was to elucidate if elevated BCAA levels are the cause or the consequence of the IR and what are the mechanisms and tissues involved in such a phenotype. Research Methods & Procedures: We have performed a 2-months follow-up on minipigs overfed on a HFHS diet and we focused on kinetics fasting and postprandial (PP) BCAA levels and BCAA catabolism in key tissues. Results: Our study of the fasting BCAA elevation reveals that BCAA accumulation in the plasma compartment is well correlated with IR markers and body weight. Further, the PP excursion of BCAA levels after the last HFHS meal was exacerbated when compared to that of the first meal, suggesting a reduced AA oxidation potential. While 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 (SCAT) was blunted after 60d of HFHS feeding. Conclusions: Our results demonstrate 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 SCAT emerges, at least in our swine model, as the more plausible metabolic explanation for the elevated blood BCAA phenotype