Inter-organ communication between BAT and muscle: role of batokines in whole body energy homeostasis

Abstract

Brown (BAT) and beige adipose cells have the capacity to produce heat (thermogenesis) due to substrate oxidation. This futile cycle is essentially regulated by the action of uncoupling protein 1 (UCP1), a protein located in the inner mitochondrial membrane of brown and beige adipocytes 1. The thermogenesis program is considered a valuable tool to counteract metabolic diseases such as obesity and diabetes. Studies suggest that biological significance of beige adipocytes may overcome simply generating heat in response to stress stimulus 2. Since white adipose tissue (WAT) secrete many adipokines, it is not unrealistic to consider that brown and beige fat cells might secrete molecules to act local or systemically modulating the metabolism. In this line, the transplantation of the inguinal WAT depots from exercised mice improves various aspects of glucose homeostasis much more than equivalent fat transplantations from sedentary mice 3. In addition, Swensson and colleagues demonstrated that brown adipose tissue release a functional cleaved C-terminal fragment (Slit2-C) in plasma that promotes thermogenic program in WAT and systemic improvements of glucose homeostasis in mice 4. While a major function of brown and beige fat is thermogenesis, recent studies from Kajimura lab and others suggest that BAT is not simply a heat-generating organ, but also function as an endocrine organ via BAT-derived secretory molecules, as referred to as "batokines". My work will aim to characterize batokines that mediate the inter-organ communication between BAT and skeletal muscle in the context of exercise and cold exposure.