Branched chain amino acids-friend or foe in the control of energy substrate turnover and insulin sensitivity?

Branched chain amino acids (BCAA) and their derivatives are bioactive molecules with pleiotropic functions in the human body. Elevated fasting blood BCAA concentrations are considered as a metabolic hallmark of obesity, insulin resistance, dyslipidaemia, nonalcoholic fatty liver disease, type 2 diabetes and cardiovascular disease. However, since increased BCAA amount is observed both in metabolically healthy and obese subjects, a question whether BCAA are mechanistic drivers of insulin resistance and its morbidities or only markers of metabolic dysregulation, still remains open. The beneficial effects of BCAA on body weight and composition, aerobic capacity, insulin secretion and sensitivity demand high catabolic potential toward amino acids and/or adequate BCAA intake. On the opposite, BCAA-related inhibition of lipogenesis and lipolysis enhancement may preclude impairment in insulin sensitivity. Thereby, the following review addresses various strategies pertaining to the modulation of BCAA catabolism and the possible roles of BCAA in energy homeostasis. We also aim to elucidate mechanisms behind the heterogeneity of ramifications associated with BCAA modulation.

Automated summary

Branched chain amino acids (BCAA) and their derivatives have multiple functions in the human body. Elevated fasting blood BCAA concentrations are considered as metabolic indicators of obesity, insulin resistance, dyslipidemia, nonalcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease. However, the question of whether BCAA are mechanistic drivers of insulin resistance and its complications or simply markers of metabolic deregulation remains unanswered. The beneficial effects of BCAA on body weight, aerobic capacity, insulin secretion, and sensitivity require high catabolic potential towards amino acids and/or adequate BCAA intake. On the other hand, BCAA-related inhibition of lipogenesis and promotion of lipolysis may prevent impairment in insulin sensitivity. Therefore, this review discusses various strategies for modulating BCAA catabolism and explores the possible roles of BCAA in energy homeostasis.