TY - JOUR T1 - Atg8 licenses adipokine nuclear exit JF - bioRxiv DO - 10.1101/2021.01.29.428913 SP - 2021.01.29.428913 AU - Michelle E. Poling AU - Camille E. Sullivan AU - Ava E. Brent AU - Terry L. Hafer AU - Akhila Rajan Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/04/02/2021.01.29.428913.abstract N2 - Adipokines released from adipocytes function as a systemic ‘adipometer’ and signal satiety1, 2. For organisms to accurately sense surplus and scarcity, adipocytes must switch adeptly between adipokine release and retention3. Despite the central requirement for adipocytes to retain adipokines to enable organismal adaptation to nutrient deprivation1, how fasting induces adipokine retention remains to be fully characterized. Here we investigated how Unpaired2 (Upd2), a fruit fly ortholog of the human adipokine Leptin4, is retained during fasting. Unexpectedly, we observe that on fasting Upd2 accumulates in the nucleus and discover that fasting-induced Upd2 nuclear accumulation is regulated by Atg8. Atg8 is a ubiquitin like protein which conjugates to a lipid moiety5. We find that, Atg8 based on its own lipidation status promotes adipokine nuclear exit in fed cells and adipokine retention in starved cells- we term this ‘adipokine licensing’. Then, we show that Atg8 lipidation is the rate-limiting step in adipokine licensing. We then illustrate how organisms use adipokine licensing to survive nutrient deprivation. Additionally, we show that adipokine nuclear retention, controlled by Atg8, stimulates post-fasting hunger; thus, Atg8-mediated nuclear retention sensitizes adipokine signaling after fasting. Hence, our findings point to a new mechanism to tackle adipokine resistance6, 7, an underlying cause of common obesity. Collectively, we have identified a novel cell-intrinsic mechanism that orchestrates systemic response to energy flux and uncovered an unexpected role for Atg8 in context-dependent protein localization.Competing Interest StatementThe authors have declared no competing interest. ER -