Local acetate inhibits brown adipose tissue function

Proc Natl Acad Sci U S A. 2021 Dec 7;118(49):e2116125118. doi: 10.1073/pnas.2116125118.

Abstract

Brown adipose tissue has been extensively studied in the last decade for its potential to counteract the obesity pandemic. However, the paracrine regulation within brown tissue is largely unknown. Here, we show that local acetate directly inhibits brown fat thermogenesis, without changing acetate levels in the circulation. We demonstrate that modulating acetate within brown tissue at physiological levels blunts its function and systemically decreases energy expenditure. Using a series of transcriptomic analyses, we identified genes related to the tricarboxylic acid cycle and brown adipocyte formation, which are down-regulated upon local acetate administration. Overall, these findings demonstrate that local acetate inhibits brown fat function.

Keywords: RNA-seq; acetate; brown adipose tissue; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / metabolism*
  • Acetates / pharmacology
  • Adipocytes, Brown / metabolism
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, Brown / physiology*
  • Adipose Tissue, White / metabolism
  • Animals
  • Citric Acid Cycle / genetics
  • Diet, High-Fat
  • Eating
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Gene Expression / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / metabolism
  • Thermogenesis / drug effects
  • Thermogenesis / physiology*
  • Transcriptome / genetics

Substances

  • Acetates