A conserved role for Smaug in energy metabolism and lipid storage

Abstract

Smaug proteins are conserved post-transcriptional regulators implicated in diverse biological functions. Here, we investigated the role of Smaug orthologs in cultured mammalian adipocytes and in the Drosophila fat body. We found that both fly Smaug and mammalian Smaug2 assemble into biomolecular condensates in adipose cells, extending previous observations in other cell types. Smaug2 depletion in 3T3-L1 adipocytes significantly reduced lipid accumulation and shifted the C/EBPβ LIP/LAP ratio toward increased expression of the inhibitory LIP isoform relative to the active LAP isoform, a pattern frequently observed under low-energy conditions. Accordingly, expression of the C/EBPβ target genes PPARγ2 and C/EBPα was reduced. Comparable phenotypes were observed in Drosophila. Loss of Smaug function in Drosophila impaired lipid storage and decreased triglyceride levels. RNAi-mediated silencing of smaug in larval fat body cells led to a severe reduction in lipid droplet accumulation and adipocyte size in a cell-autonomous manner. Finally, adult flies with fat body-specific smaug knockdown exhibited increased sensitivity to nutritional stress. Collectively, these findings identify a conserved role for Smaug proteins in adipose tissue homeostasis.