Nuclear Retention of Leptin/Upd2 Regulates Organismal Resilience to Nutrient Extremes

Abstract

Adipocytes release adipokines to function as a systemic ‘adipometer’ and signal satiety. For organisms to function effectively, adipocytes must switch adeptly between adipokine release and retention. We investigated how Unpaired2 (Upd2), a Drosophila ortholog of the human adipokine Leptin, is retained during fasting. Unexpectedly, we find that fasting induces Upd2 nuclear accumulation; and that Upd2 nuclear retention is regulated by Atg8. Atg8 is a ubiquitin like protein which conjugates to a lipid moiety. In fed cells, Atg8 localizes both to the nucleus and the cytoplasm. On fasting Atg8 lipidation levels increase, and the nuclear pool of Atg8 is depleted. We find that Atg8 lipidation is the rate limiting step in Upd2 nuclear exit. Illustrating the physiological significance of Atg8-mediated adipokine nuclear retention, we show that this mechanism promotes starvation resilience and post-fasting hunger. Our findings uncover a new facet of Atg8 biology in regulating context-dependent nuclear export and protein localization.

Fat- and sugar-induced signals regulate sweet and fat taste perception in Drosophila

“…Interestingly, the Upd2:GFP was taken up and localized to the nucleus of taste neurons ( Figure 4H ). Recently the nucleus was also identified as an Upd2 reservoir in other tissues, 34 suggesting that Upd2 is taken up and stored in taste neurons. Interestingly, Hh secreted from the gut is stored in taste sensilla lymph.…”