Beige adipose tissue-derived extracellular vesicles: a potent metabolic regulator and a novel remedy for nonalcoholic fatty liver disease

Adipose tissue (AT) is an essential metabolic and endocrine organ, which are categorized into the white adipose tissue (WAT) and the brown adipose tissue (BAT), as well as the beige adipose tissue (BeAT) that derives from WAT browning. Notably, extracellular vesicles (EVs), especially tissue-produced EVs, have been recognized to be critical players in multiple physiological and pathophysiological settings and provide efficient strategy for disease treatment. However, little is known about the BeAT-derived EVs (BeEVs). In this study, we induced BeEV formation by cold stimulation and extracted EVs from three kinds of AT via enzyme digestion combined with gradient centrifugation. The isolated BeEVs possess typical morphological, structural and marker characteristics of EVs. Proteomics analysis further demonstrated that the BeEVs hold a distinct protein profile while are enriched with multiple metabolic regulatory proteins. Importantly, systemic injection of BeEVs into mice improved metabolic dysfunction in a nonalcoholic fatty liver disease (NAFLD) model induced by high-fat diet (HFD). Moreover, we demonstrated that the BeEVs alleviated liver steatosis via decreasing the lipogenesis. These findings promote the understanding of AT-EVs and shed light on the isolation, identification and applications of BeEVs as a potent metabolic regulator and novel remedy for metabolic diseases.