Brown adipocyte-derived exosomal miR-132-3p suppress hepatic Srebf1 expression and thereby attenuate expression of lipogenic genes

Biochem Biophys Res Commun. 2020 Sep 24;530(3):500-507. doi: 10.1016/j.bbrc.2020.05.090. Epub 2020 Jun 25.

Abstract

Recent evidence has revealed a novel signaling mechanism through which brown adipose tissue (BAT)-derived exosomal microRNAs (miRNAs) influence hepatic gene expression. Here, we uncover neuronal control of these miRNAs and identify exosomal miR-132-3p as a regulator of hepatic lipogenesis under cold stress conditions. Norepinephrine, a sympathetic nervous system neurotransmitter mediating cold-induced BAT activation, altered the composition of brown adipocyte (BAC)-derived exosomal miRNAs; among them, miR-132-3p was significantly induced. The isolated BAC-derived exosomes suppressed expression of hepatic Srebf1, a predicted target of miR-132-3p. In an indirect co-culture system, BACs suppressed expression of hepatic Srebf1 and its target lipogenic genes; this effect was not seen with miR-132-3p-inhibited BACs. Srebf1 was experimentally validated as an miR-132-3p target. Cold stimuli consistently induced miR-132-3p expression in BAT and attenuated Srebf1 expression in the liver. Our results suggest that BAT-derived exosomal miR-132-3p acts as an endocrine factor that regulates hepatic lipogenesis for cold adaptation.

Keywords: Brown adipocytes; Exosome; Hepatocytes; Srebf1; miR-132-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Brown / metabolism*
  • Animals
  • Cells, Cultured
  • Down-Regulation
  • Exosomes / genetics
  • Lipogenesis
  • Liver / metabolism*
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • Norepinephrine / metabolism
  • Sterol Regulatory Element Binding Protein 1 / genetics*
  • Up-Regulation

Substances

  • MIRN132 microRNA, mouse
  • MicroRNAs
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Norepinephrine