A new era of understanding in vivo metabolic flux in thermogenic adipocytes

Nonshivering thermogenesis by brown adipose tissue (BAT) is an adaptive mechanism for maintaining body temperature in cold environments. BAT is critical in rodents and human infants and has substantial influence on adult human metabolism. Stimulating BAT therapeutically is also being investigated as a strategy against metabolic diseases because of its ability to function as a catabolic sink. Thus, understanding how brown adipocytes and the related brite/beige adipocytes use nutrients to fuel their demanding metabolism has both basic and translational implications. Recent advances in mass spectrometry and isotope tracing are improving the ability to study metabolic flux in vivo. Here, we review how such strategies are advancing our understanding of adipocyte thermogenesis and conclude with key future questions. •Metabolomics and isotope tracing is advancing our understanding of brown adipose tissue (BAT).•Arteriovenous metabolomics can reveal BAT metabolic fluxes. Brown adipocytes prefer glucose but exhibit substrate flexibility.•Glucose may support UCP1-depenedent and UCP1-indepenent thermogenic cycles.•Defining BAT metabolism is key to realizing its biological function and therapeutic potential.