snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesis

Nature. 2020 Nov;587(7832):98-102. doi: 10.1038/s41586-020-2856-x. Epub 2020 Oct 28.

Abstract

Adipose tissue is usually classified on the basis of its function as white, brown or beige (brite)1. It is an important regulator of systemic metabolism, as shown by the fact that dysfunctional adipose tissue in obesity leads to a variety of secondary metabolic complications2,3. In addition, adipose tissue functions as a signalling hub that regulates systemic metabolism through paracrine and endocrine signals4. Here we use single-nucleus RNA-sequencing (snRNA-seq) analysis in mice and humans to characterize adipocyte heterogeneity. We identify a rare subpopulation of adipocytes in mice that increases in abundance at higher temperatures, and we show that this subpopulation regulates the activity of neighbouring adipocytes through acetate-mediated modulation of their thermogenic capacity. Human adipose tissue contains higher numbers of cells of this subpopulation, which could explain the lower thermogenic activity of human compared to mouse adipose tissue and suggests that targeting this pathway could be used to restore thermogenic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / metabolism
  • Adipocytes / metabolism*
  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / metabolism
  • Adult
  • Aged
  • Aldehyde Dehydrogenase 1 Family / genetics
  • Aldehyde Dehydrogenase 1 Family / metabolism
  • Animals
  • Cell Nucleus / genetics*
  • Cell Separation
  • Cytochrome P-450 CYP2E1 / genetics
  • Cytochrome P-450 CYP2E1 / metabolism
  • Energy Metabolism
  • Female
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Paracrine Communication
  • RNA-Seq*
  • Retinal Dehydrogenase / genetics
  • Retinal Dehydrogenase / metabolism
  • Single-Cell Analysis*
  • Thermogenesis / genetics*
  • Young Adult

Substances

  • Acetates
  • Cytochrome P-450 CYP2E1
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • ALDH1A1 protein, mouse
  • Retinal Dehydrogenase