An autonomous metabolic role for Spen

PLoS Genet. 2017 Jun 22;13(6):e1006859. doi: 10.1371/journal.pgen.1006859. eCollection 2017 Jun.

Abstract

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.

MeSH terms

  • Adipose Tissue / growth & development
  • Adipose Tissue / metabolism
  • Animals
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster
  • Energy Metabolism / genetics*
  • Gene Expression Regulation
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics*
  • Humans
  • Larva / genetics
  • Larva / growth & development
  • Larva / metabolism
  • Mice
  • Mutation
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics*
  • Signal Transduction / genetics

Substances

  • Drosophila Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Spen protein, Drosophila