(Correspondent: CHANG Yu) On 5 September, the international authoritative journal Nature Communications published online the results of Professor CHEN Yong's team from Affiliated Tongji Hospital of HUST. The team discovered that Sortilin played a critical role in the activation of beige adipocytes and it regulated fatty acid oxidation in adipose tissue, which provides a new potential target for the treatment of metabolic diseases.

Beige adipocytes, a special type of adipocytes, are mostly found in subcutaneous white adipose tissue, and can be converted to a ‘brown-like state’ by prolonged cold exposure or β-adrenergic agonist stimulation, thus possessing a strong capacity of thermogenesis and higher energy expenditure. This transition is important for treating obesity and its associated metabolic disorders. However, the molecular mechanism by which beige adipocytes preferentially use fatty acid oxidation to generate heat has not been fully elucidated.

The team found that Sortilin, a sorting protein involved in endosomal transport in cells, played a key role in beige fat activation. It could affect the fatty acid oxidation process in adipocytes by promoting the translocation of acyl coenzyme A synthase long chain family member 1 (ACSL1) from mitochondria to endolysosomes for degradation. When Sortilin was absent in adipocytes, mitochondrial ACSL1 levels were significantly increased, which in turn activated the AMPK/PGC1α signalling pathway and promoted beige fat activation and thermogenesis. This change rendered adipocytes more resistant in response to a high-fat diet, thus preventing the development of obesity and insulin resistance.

CHEN Yong said that this study not only reveals a new mechanism of how Sortilin works in adipocyte thermogenesis, but also provides new apporach for the treatment of metabolic diseases. By regulating the expression or function of Sortilin, the thermogenic capacity and energy consumption of adipocytes can be altered, thus achieving the goal of treating metabolic diseases such as obesity and diabetes.