An autonomous metabolic role for Spen

Preventing obesity requires a precise balance between deposition into and mobilization from fat stores,but regulatory mechanisms are incompletely understood. drosophila split ends (spen) is the founding member of a conserved family of rna-binding proteins involved in transcriptional regulation and frequently mutated in human cancers. we find that manipulating spen expression alters larval fat levels in a cell-autonomous manner. spen-depleted larvae had defects in energy liberation from stores,including starvation sensitivity and major changes in the levels of metabolic enzymes and metabolites,particularly those involved in β-oxidation. spenito,a small spen family member,counteracted spen function in fat regulation. finally,mouse spen and spenito transcript levels scaled directly with body fat in vivo,suggesting a conserved role in fat liberation and catabolism. this study demonstrates that spen is a key regulator of energy balance and provides a molecular context to understand the metabolic defects that arise from spen dysfunction. © 2017 hazegh et al.