A synergistic anti-obesity effect by a combination of capsinoids and cold temperature through promoting beige adipocyte biogenesis.

Beige adipocytes emerge postnatally within the white adipose tissue (WAT) in response to certain environmental cues, such as chronic cold exposure. Because of its highly recruitable nature and relevance to adult humans, beige adipocytes have gained much attention as an attractive cellular target for anti-obesity therapy. However, molecular circuits that preferentially promote beige adipocyte biogenesis remain poorly understood. Here, we report that a combination of mild cold exposure at 17°C and capsinoids, a non-pungent analog of capsaicin, synergistically and preferentially promotes beige adipocyte biogenesis and ameliorate diet-induced obesity. Gain- and loss-of-function studies show that the combination of capsinoids and cold exposure synergistically promotes beige adipocyte development through the β2-adrenoceptor signaling pathway. This synergistic effect on beige adipocyte biogenesis occurs through an increased half-life of PRDM16, a dominant transcriptional regulator of brown/beige adipocyte development. Our observations document a previously unappreciated molecular circuit that controls beige adipocyte biogenesis and suggest a plausible approach to increase whole body energy expenditure by combining dietary components and environmental cues.