The secretory function of BECN1 in metabolic regulation.

Kenta Kuramoto, Congcong He

Autophagy 2021 Oct

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Macroautophagy/autophagy is primarily considered as a degradative pathway via the lysosome, yet the secretory functions of autophagy proteins have recently been unveiled. Autophagy proteins have been implicated in metabolic organ development, homeostasis and function, and deficiency in autophagy is associated with metabolic disorders. However, the molecular mechanisms by which autophagy proteins regulate energy metabolism and insulin sensitivity were unclear. We previously showed that systemic activation of autophagy by a hyperactive BECN1F121A mutant reduces insulin storage in islets but improves insulin sensitivity systemically. In our recent study, we found that BECN1 functions in adipose tissue to systemically regulate energy metabolism. Adipose-specific expression of BECN1F121A is sufficient to improve systemic insulin sensitivity without negatively affecting pancreatic insulin storage. We demonstrated that BECN1 interacts with exocyst subunit proteins and facilitates the secretion of an adipokine, ADIPOQ (adiponectin, C1Q and collagen domain containing), in adipose tissue. Thus, our findings suggest that BECN1 regulates insulin sensitivity in a non-degradative and non-cell autonomous manner by facilitating ADIPOQ secretion. Our study also highlighted the distinct functions of autophagy proteins in different metabolic tissues.