Inhibition of high-fat diet-induced inflammatory responses in adipose tissue by SF1-expressing neurons of the ventromedial hypothalamus

Cell Rep. 2023 Jun 27;42(6):112627. doi: 10.1016/j.celrep.2023.112627. Epub 2023 Jun 19.

Abstract

Inflammation and thermogenesis in white adipose tissue (WAT) at different sites influence the overall effects of obesity on metabolic health. In mice fed a high-fat diet (HFD), inflammatory responses are less pronounced in inguinal WAT (ingWAT) than in epididymal WAT (epiWAT). Here we show that ablation and activation of steroidogenic factor 1 (SF1)-expressing neurons in the ventromedial hypothalamus (VMH) oppositely affect the expression of inflammation-related genes and the formation of crown-like structures by infiltrating macrophages in ingWAT, but not in epiWAT, of HFD-fed mice, with these effects being mediated by sympathetic nerves innervating ingWAT. In contrast, SF1 neurons of the VMH preferentially regulated the expression of thermogenesis-related genes in interscapular brown adipose tissue (BAT) of HFD-fed mice. These results suggest that SF1 neurons of the VMH differentially regulate inflammatory responses and thermogenesis among various adipose tissue depots and restrain inflammation associated with diet-induced obesity specifically in ingWAT.

Keywords: CP: Metabolism; CP: Neuroscience; adipose tissue; diet-induced obesity; inflammation; macrophage; steroidogenic factor 1; sympathetic nerve; ventromedial hypothalamus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / metabolism
  • Animals
  • Diet, High-Fat* / adverse effects
  • Energy Metabolism / physiology
  • Hypothalamus / metabolism
  • Inflammation / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism
  • Obesity* / metabolism
  • Steroidogenic Factor 1* / genetics
  • Steroidogenic Factor 1* / metabolism
  • Steroidogenic Factor 1* / pharmacology
  • Thermogenesis

Substances

  • Steroidogenic Factor 1