The autophagy protein Becn1 improves insulin sensitivity by promoting adiponectin secretion via exocyst binding

Kenta Kuramoto, Yoon Jin Kim, Jung Hwa Hong, Congcong He*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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 Becn1F121A 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 Becn1F121A 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.

Original languageEnglish (US)
Article number109184
JournalCell reports
Volume35
Issue number8
DOIs
StatePublished - May 25 2021

Keywords

  • AMPK
  • Becn1
  • Sec6
  • adiponectin
  • adipose tissue
  • autophagy
  • exocyst
  • glucose tolerance
  • insulin sensitivity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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