Branched-chain and glucogenic amino acids predict brown fat recruitment and metabolic clearance in adults with overweight or obesity.

Abstract

The relationship between circulating amino acids (AAs), particularly branched-chain amino acids (BCAAs), and brown adipose tissue (BAT) recruitment and their subsequent fate during thermogenesis remains poorly defined. We investigated the longitudinal changes and predictive role of serum AAs metabolism in 25 participants with overweight or obesity following a 12-wk BAT-activating intervention (curcumin supplementation and/or cold exposure). Participants were stratified into BAT responders (n = 8) and nonresponders (n = 17) via fusion 18-fluorine fluorodeoxyglucose positron emission tomography-magnetic resonance (¹⁸F-FDG PET/MR) imaging. BAT responders exhibited a significant systemic clearance of several AAs, including phenylalanine, glutamine, asparagine, and glycine, whereas nonresponders showed a significant increase in valine and total BCAAs. Multiple linear regression analysis identified baseline levels of total BCAAs (β = 0.81, P = 0.007) and glucogenic AAs (β = 0.65, P < 0.001) as independent positive predictors of BAT activity. Furthermore, the magnitude of BAT activation was inversely associated with the longitudinal change in these AAs, suggesting that activated BAT serves as a significant site for systemic AA clearance. We conclude that circulating branched-chain and glucogenic AAs are closely associated with the capacity for BAT recruitment and activation. The resulting enhanced metabolic demand transforms the activated BAT into an effective site for systemic AA clearance and improved metabolic homeostasis.NEW & NOTEWORTHY Elevated circulating branched-chain amino acids (BCAAs) are established biomarkers of metabolic dysfunction, but the regulatory role of human brown adipose tissue (BAT) remains unclear. We demonstrate that high baseline BCAA and glucogenic amino acid levels independently predict the capacity of BAT recruitment. Furthermore, successful BAT activation is associated with the systemic clearance of these metabolites. These findings suggest that BAT serves as a key regulator of amino acid homeostasis and represents a potential therapeutic target for addressing metabolic disorders in adults.