The β-galactoside binding lectins, termed galectins, have garnered immense scientific interest for their ability to regulate diverse biologic processes, from adaptive immune responses to epithelial cell biology. Yet, an understanding of the role of galectins in regulating developmental processes has been limited by the functional redundancies across galectins which exist in vertebrates. Thus, we utilized the model organism Drosophila, which contains a single galectin ortholog, to ask what are the developmental requirements for galectins in metazoans. Using CRISPR/Cas9, we generated deletions in the galectin locus which efficiently eliminated galectin protein (Dmgal) across tissues. Intriguing, loss of galectin is not essential in Drosophila as animals ecclose with relatively minimal phenotypes. Among these, dmgal-deficient animals are significantly smaller than their wild-type counterparts. Moreover, when challenged to nutrient-deprivation or Paraquat-toxicity, dmgal-deficient animals show marked sensitivity compared to their wild-type animals. Transcriptomics analysis reveals that dmgal-deficient animals show significantly different profiles than their wild-type counterparts, with enrichment in metabolic pathways. Similarly, metabolomics shows distinct profiles from dmgal-deficient and wild-type animals with significant alterations in amino acid and nutrient-sensing pathways. Finally, analysis of the Drosophila fat body reveals alterations in fat content, and tissue specific deletion of galectin in this organ renders animals sensitive to nutrient loss. Taken together, these findings uncover a novel role for dmgal in regulating Drosophila metabolism in the Drosophila fat body, and may provide clues into the role of galectins in regulating insulin sensitivity and NASH/NAFLD in vertebrates.
