ABSTRACT
Adipokines released from the adipocytes function as a systemic adipometer; they impinge on neural circuits to signal nutrient status. On starvation, adipokines must be retained to signal energy deficit; else, it significantly reduces starvation survival. But how fat cells retain adipokines is unclear. Here, we demonstrate that Atg8, a cell-intrinsic autophagy factor, regulates the starvation-induced acute retention of the Leptin Drosophila ortholog Upd2. We show that on starvation, as a direct consequence of Atg8’s lipidation, Upd2 accumulates in the nucleus. We illustrate that Upd2’s nuclear retention is critical to fat mobilization and increased starvation resilience. Furthermore, nuclear Upd2 promotes the expression of a secreted innate immune gene signature. This hints at an unanticipated connection between adipokine nuclear retention and increased innate immunity. In conclusion, we propose that, during starvation, Atg8’s role is not just limited to autophagy but is critical for withholding adipokines in the nucleus to promote starvation resilience.
In fed state Upd2 requires Atg8 for nuclear exit and cytosolic localization.
Atg8’s lipidation on starvation results in Upd2’s nuclear accumulation.
Upd2 nuclear retention on starvation increases fat mobilization and post-starvation hunger.
On starvation Upd2 nuclear retention increases expression of a secreted innate immune signature.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Figure 6 RNAseq for testing the model.
