Transcriptional Regulation of Lipid Metabolism by Wnt Signaling and Hox Protein Cues

Metabolic processes such as lipogenesis, lipolysis, and fatty acid β-oxidation in adipocytes are essential for maintaining energy balance in insects and more complex animals. Dysregulation of these processes is associated with metabolic disorders, cancer, and other diseases. While the enzymatic reactions and regulatory mechanisms of metabolic enzymes-such as allosteric control and post-translational modifications in response to glucose, insulin, and other hormonal fluctuations-are well documented, their transcriptional regulation remains less understood. Using the transcription of lipogenic genes, particularly FASN1 (which encodes fatty acid synthase 1), as a model, we summarize recent insights into how Wnt/Wingless signaling and developmental cues, especially Hox proteins, regulate metabolic enzyme transcription in both Drosophila and mammals. Furthermore, we explore how the interplay between Wnt/Wg signaling and Hox proteins controls regional adipocyte differences in Drosophila and discuss the broader implications of adipocyte heterogeneity for evolution and human diseases, particularly tumorigenesis.