FGF signaling promotes spreading of fat body precursors necessary for adult adipogenesis in Drosophila

PLoS Biol. 2023 Mar 22;21(3):e3002050. doi: 10.1371/journal.pbio.3002050. eCollection 2023 Mar.

Abstract

Knowledge of adipogenetic mechanisms is essential to understand and treat conditions affecting organismal metabolism and adipose tissue health. In Drosophila, mature adipose tissue (fat body) exists in larvae and adults. In contrast to the well-known development of the larval fat body from the embryonic mesoderm, adult adipogenesis has remained mysterious. Furthermore, conclusive proof of its physiological significance is lacking. Here, we show that the adult fat body originates from a pool of undifferentiated mesodermal precursors that migrate from the thorax into the abdomen during metamorphosis. Through in vivo imaging, we found that these precursors spread from the ventral midline and cover the inner surface of the abdomen in a process strikingly reminiscent of embryonic mesoderm migration, requiring fibroblast growth factor (FGF) signaling as well. FGF signaling guides migration dorsally and regulates adhesion to the substrate. After spreading is complete, precursor differentiation involves fat accumulation and cell fusion that produces mature binucleate and tetranucleate adipocytes. Finally, we show that flies where adult adipogenesis is impaired by knock down of FGF receptor Heartless or transcription factor Serpent display ectopic fat accumulation in oenocytes and decreased resistance to starvation. Our results reveal that adult adipogenesis occurs de novo during metamorphosis and demonstrate its crucial physiological role.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis*
  • Adipose Tissue / metabolism
  • Animals
  • Drosophila* / metabolism
  • Fat Body / metabolism
  • Fibroblast Growth Factors / metabolism
  • Receptors, Fibroblast Growth Factor / metabolism

Substances

  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors

Grants and funding

This work was funded by grants 32150710524 and 91854207 from the National Natural Science Foundation of China (https://nsfc.gov.cn) and grant PID2021-122119NB-I00 from Ministerio de Ciencia e Innovación (https://www.ciencia.gob.es), all to J.C.P.-P. J.C.P.-P. was also funded by the “Severo Ochoa” Program for Centers of Excellence (CEX2021-001165-S) from Ministerio de Ciencia e Innovación. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.