miR-26 suppresses adipocyte progenitor differentiation and fat production by targeting Fbxl19

Genes Dev. 2019 Oct 1;33(19-20):1367-1380. doi: 10.1101/gad.328955.119. Epub 2019 Sep 5.

Abstract

Fat storage in adult mammals is a highly regulated process that involves the mobilization of adipocyte progenitor cells (APCs) that differentiate to produce new adipocytes. Here we report a role for the broadly conserved miR-26 family of microRNAs (miR-26a-1, miR-26a-2, and miR-26b) as major regulators of APC differentiation and adipose tissue mass. Deletion of all miR-26-encoding loci in mice resulted in a dramatic expansion of adipose tissue in adult animals fed normal chow. Conversely, transgenic overexpression of miR-26a protected mice from high-fat diet-induced obesity. These effects were attributable to a cell-autonomous function of miR-26 as a potent inhibitor of APC differentiation. miR-26 blocks adipogenesis, at least in part, by repressing expression of Fbxl19, a conserved miR-26 target without a previously known role in adipocyte biology that encodes a component of SCF-type E3 ubiquitin ligase complexes. These findings have therefore revealed a novel pathway that plays a critical role in regulating adipose tissue formation in vivo and suggest new potential therapeutic targets for obesity and related disorders.

Keywords: Fbxl19; adipocyte progenitor cell; adipogenesis; miR-26; microRNA; obesity; white adipose tissue.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / genetics*
  • Animals
  • Cell Differentiation / genetics*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Diet, High-Fat
  • F-Box Proteins / genetics*
  • F-Box Proteins / metabolism*
  • Gene Expression
  • Gene Knockdown Techniques
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Obesity / genetics*
  • Stem Cells / cytology*

Substances

  • DNA-Binding Proteins
  • F-Box Proteins
  • FBXL19 protein, mouse
  • MicroRNAs
  • Mirn26 microRNA, mouse