| First Author | Kuramoto K | Year | 2021 |
| Journal | Cell Rep | Volume | 35 |
| Issue | 8 | Pages | 109184 |
| PubMed ID | 34038729 | Mgi Jnum | J:310052 |
| Mgi Id | MGI:6717040 | Doi | 10.1016/j.celrep.2021.109184 |
| Citation | Kuramoto K, et al. (2021) The autophagy protein Becn1 improves insulin sensitivity by promoting adiponectin secretion via exocyst binding. Cell Rep 35(8):109184 |
| abstractText | Autophagy dysregulation is implicated in metabolic diseases, including type 2 diabetes. However, the mechanism by which the autophagy machinery regulates metabolism is largely unknown. Autophagy is generally considered a degradation process via lysosomes. Here, we unveil a metabolically important non-cell-autonomous, non-degradative mechanism regulated by the essential autophagy protein Becn1 in adipose tissue. Upon high-fat diet challenge, autophagy-hyperactive Becn1(F121A) mice show systemically improved insulin sensitivity and enhanced activation of AMP-activated protein kinase (AMPK), a central regulator of energy homeostasis, via a non-cell-autonomous mechanism mediated by adiponectin, an adipose-derived metabolic hormone. Adipose-specific Becn1(F121A) expression is sufficient to activate AMPK in non-adipose tissues and improve systemic insulin sensitivity by increasing adiponectin secretion. Further, Becn1 enhances adiponectin secretion by interacting with components of the exocyst complex via the coiled-coil domain. Together, our study demonstrates that Becn1 improves insulin sensitivity by facilitating adiponectin secretion through binding the exocyst in adipose tissue. |
