Thermogenic adipose tissue in energy regulation and metabolic health

The ability to generate thermogenic fat could be a targeted therapy to thwart obesity and improve metabolic health. Brown and beige adipocytes are two types of thermogenic fat cells that regulate energy balance. Both adipocytes share common morphological, biochemical, and thermogenic properties. Yet, recent evidence suggests unique features exist between brown and beige adipocytes, such as their cellular origin and thermogenic regulatory processes. Beige adipocytes also appear highly plastic, responding to environmental stimuli and interconverting between beige and white adipocyte states. Additionally, beige adipocytes appear to be metabolically heterogenic and have substrate specificity. Nevertheless, obese and aged individuals cannot develop beige adipocytes in response to thermogenic fat-inducers, creating a key clinical hurdle to their therapeutic promise. Thus, elucidating the underlying developmental, molecular, and functional mechanisms that govern thermogenic fat cells will improve our understanding of systemic energy regulation and strive for new targeted therapies to generate thermogenic fat. This review will examine the recent advances in thermogenic fat biogenesis, molecular regulation, and the potential mechanisms for their failure.