Year: 2017
Type: article
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.
Source: PLoS Genetics
Institution: University of Colorado Anschutz
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: Boettcher Foundation, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Mechanisms of fat regulation by conserved anti-obesity genes, G1625418467, G1906577294, G215709867, Postnatal Actions of Maternal Obesity on Neonatal Metabolic Health, G3733990746, Neuronal Inputs of Body Fat Regulation, G812494088, Predoctoral Training Program in Molecular Biology, G9000016497, G9000247170
OpenAlex ID: W2642851864