A Study of the Activation of Brown Adipose Tissue by Food Ingredients and Their Anti-Obesity Effects

(JSNFS Award for Young Investigators (2022))

Abstract

Brown adipose tissue (BAT) is a site responsible for non-shivering thermogenesis during cold exposure, contributing to the control of body temperature and adiposity. In humans, although a decrease of BAT activity with aging is associated with the development of obesity, chronic activation of BAT through repeated cold exposure can re-activate BAT, thereby decreasing body fat mass. To explore practical anti-obesity strategies that could be an alternative to cold exposure, we focused on food ingredients exerting agonistic activity against temperature-sensitive TRP channels. We then investigated the thermogenic effects of non-pungent capsaicin analogs (capsinoids) and green tea catechins, both of which can stimulate temperature-responsive TRP channels, and their relationship to BAT activity in healthy volunteers. We found that single ingestion of capsinoids or catechins significantly increased energy expenditure in subjects with active BAT, but not in those without. Moreover, repeated ingestion of these substances increased BAT-dependent thermogenic capacity even in individuals who had lost their BAT activity, suggesting successful recruitment of BAT. Additionally, through comprehensive analysis of circulating metabolites in mice and humans, we searched for new nutritional factors for control of BAT function and identified branched-chain amino acids as a key energy substrate for BAT thermogenesis. These our findings support the development of practical, efficient dietary regimens capable of boosting BAT thermogenesis and preventing lifestyle-related diseases.