Fig. 6 |. Harnessing thermogenic fat activity for precision medicine.

Nutritional supplementation with branched-chain amino acids (BCAAs) has differential outcomes in humans depending on their metabolic state: BCAAs are known to enhance energy expenditure, and, paradoxically, higher circulating levels of BCAAs are found in individuals with obesity and/or individuals with diabetes who exhibit lower energy expenditure^125,128,193. BCAAs are actively imported into brown fat mitochondria and stimulate thermogenesis, and thus BCAA supplementation enhances energy expenditure for those individuals who are capable of oxidizing BCAAs in their brown adipose tissue (BAT) depots¹²⁴. By contrast, impaired BAT activity as a BCAA sink, as often seen in obesity and ageing, reduces BCAA clearance, thereby increasing circulating BCAA levels, leading to the overflow of BCAAs into skeletal muscle and resulting in insulin resistance¹²³. Hence, stratification of human individuals based on their BAT activity (using ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) or magnetic resonance imaging (MRI)) can be explored as a component of precision medicine to tailor therapeutic or dietary interventions to the patient’s metabolic state.