Adipocyte heterogeneity regulated by the Bithorax Complex-Wnt signaling crosstalk in Drosophila

TL;DR

This study shows how Wnt signaling and Hox genes work together to create differences in fat cells in fruit fly larvae.

Contribution

The study reveals a feedforward loop between Wnt signaling and BX-C Hox genes that defines adipocyte heterogeneity in Drosophila.

Findings

Abdominal adipocytes express abd-A and Abd-B, while thoracic adipocytes do not.

Wnt signaling enhances lipid mobilization in abdominal but not thoracic adipocytes.

A feedforward loop between Wnt signaling and BX-C genes reinforces regional adipocyte differences.

Abstract

Adipocytes play essential roles in lipid metabolism and energy homeostasis, with regional differences affecting their functions and disease susceptibility. However, the mechanisms underlying this regional heterogeneity remain unclear. Here we demonstrate that the Bithorax Complex (BX-C) genes, specifically abdominal A (abd-A) and Abdominal B (Abd-B), define regional differences in Drosophila larval adipocytes. Abdominal adipocytes, expressing abd-A and Abd-B exhibit unique characteristics compared to thoracic adipocytes, with active Wnt/Wingless signaling further amplifying these regional differences. Depleting abd-A and Abd-B in adipocytes delays larval-pupal transition, causes pupal lethality, and attenuates the expression of Wnt/Wg target genes, thereby dampening Wnt signaling-induced lipid mobilization. Additionally, Wnt signaling enhances the transcription of abd-A and Abd-B, establishing a feedforward loop that reinforces the interplay between Wnt signaling and BX-C genes. These findings reveal how the cell-autonomous expression of BX-C genes defines adipocyte heterogeneity, a process further modulated by Wnt signaling in Drosophila larvae.

Regional adipocyte heterogeneity supports metabolic homeostasis, yet mechanisms remain unclear. This study reveals that the interplay between Wnt/Wingless signaling and Hox proteins (Abd-A and Abd-B) defines the regional heterogeneity of larval fat body in Drosophila.

Active Wnt/Wg signaling stimulates lipid mobilization in the abdominal adipocytes, but not in the thoracic adipocytes in Drosophila larvae.The Bithorax complex (BX-C) Hox genes, abd-A and Abd-B, are expressed in abdominal adipocytes but are absent in thoracic adipocytes.Abd-A and Abd-B play a permissive role in modulating both Wnt-activated and Wnt-repressed gene expression in abdominal adipocytes.Adipocytes lacking abd-A and Abd-B expression – whether thoracic or occasionally abdominal – fail to activate or repress Wnt target genes, rendering these adipocytes unresponsive to Wnt signaling-induced lipid mobilization.Wnt signaling stimulates abd-A and Abd-B transcription, creating a feedforward loop that reinforces the interaction between Wnt signaling and BX-C genes.

Active Wnt/Wg signaling stimulates lipid mobilization in the abdominal adipocytes, but not in the thoracic adipocytes in Drosophila larvae.

The Bithorax complex (BX-C) Hox genes, abd-A and Abd-B, are expressed in abdominal adipocytes but are absent in thoracic adipocytes.

Abd-A and Abd-B play a permissive role in modulating both Wnt-activated and Wnt-repressed gene expression in abdominal adipocytes.

Adipocytes lacking abd-A and Abd-B expression – whether thoracic or occasionally abdominal – fail to activate or repress Wnt target genes, rendering these adipocytes unresponsive to Wnt signaling-induced lipid mobilization.

Wnt signaling stimulates abd-A and Abd-B transcription, creating a feedforward loop that reinforces the interaction between Wnt signaling and BX-C genes.

Regional adipocyte heterogeneity supports metabolic homeostasis, yet mechanisms remain unclear. This study reveals that the interplay between Wnt/Wingless signaling and Hox proteins (Abd-A and Abd-B) defines the regional heterogeneity of larval fat body in Drosophila.

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