School of Life Sciences, Tsinghua University, Beijing, China.
Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Parc Científic de Barcelona, Barcelona, Spain.
PLoS Biol. 2023 Mar 22;21(3):e3002050. doi: 10.1371/journal.pbio.3002050. eCollection 2023 Mar.
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.
了解脂肪生成机制对于理解和治疗影响机体代谢和脂肪组织健康的疾病至关重要。在果蝇中，成熟的脂肪组织（脂肪体）存在于幼虫和成虫中。与众所周知的幼虫脂肪体从胚胎中胚层发育不同，成虫脂肪生成一直是个谜。此外，其生理意义的确凿证据也缺乏。在这里，我们表明成年脂肪体源自一群未分化的中胚层前体，这些前体在变态期间从胸部迁移到腹部。通过体内成像，我们发现这些前体从腹中线扩散，并以惊人的方式覆盖腹部的内表面，这一过程与胚胎中胚层的迁移非常相似，需要成纤维细胞生长因子 (FGF) 信号转导。FGF 信号转导指导向背部迁移，并调节与基质的黏附。扩散完成后，前体分化涉及脂肪积累和细胞融合，产生成熟的双核和四核脂肪细胞。最后，我们表明，通过敲低 FGF 受体 Heartless 或转录因子 Serpent 来破坏成虫脂肪生成的果蝇中，脂肪细胞在卵母细胞中异位积累，并降低了对饥饿的抵抗力。我们的结果表明，成虫脂肪生成是在变态期间从头发生的，并证明了它的关键生理作用。
