Comparative transcriptome and Lipidome analyses suggest a lipid droplet-specific response to heat exposure of brown adipose tissue in normal and obese mice

Life Sci. 2022 Jun 15:299:120540. doi: 10.1016/j.lfs.2022.120540. Epub 2022 Apr 8.

Abstract

Aims: In mammals, heat stress (HS) from high-temperature environments has multiple adverse effects on the well-being of the organism. Brown adipose tissue (BAT) is a thermogenesis tissue that protects against obesity, and as an endocrine organ that regulates the systemic metabolism, but it is unclear how heat stress affects BAT in normal and obese subjects. Understanding the transcriptomic profiles and lipidomics of BAT upon heat exposure provides insights into the adaptive changes associated with this process.

Materials and methods: We constructed heat treatment (40 °C, 4 h) models for normal and obese mice, observed the effect of heat treatment on interscapular BAT (iBAT) and performed an assay for iBAT with RNA-seq and lipidomics to compare transcriptional programs and lipid dynamics.

Key findings: In normal mice, heat treatment caused an iBAT damage by decreasing the expression of genes involved in thermogenesis, adipogenesis and lipid metabolism. Furthermore, HS disturbed the acyl-chain composition of triacylglycerols (TAGs) and glycerophospholipids (PEs, PCs and CLs), accelerated the production of cholesterol esters, and caused the formation of giant lipid droplets rich in cholesterol esters in iBAT. Unexpectedly, in obese mice, heat treatment had a smaller effect on iBAT by improving the composition of the saturated glycerolipids, PEs and PCs and increasing the proportion of oxidized lipid in lipid droplets.

Significance: Our findings proved lipid droplets participated in the regulation of lipid components of iBAT in normal and obese mice after heat treatment, which provided a new view for the understanding of the adaptation of iBAT to high-temperature environments.

Keywords: Heat exposure; Hyperthermia adaptation; Lipid droplets; Obesity; iBAT damage.

MeSH terms

  • Adipose Tissue, Brown* / metabolism
  • Animals
  • Cholesterol Esters / metabolism
  • Humans
  • Lipid Droplets
  • Lipidomics
  • Mammals
  • Mice
  • Mice, Obese
  • Obesity / metabolism
  • Thermogenesis
  • Transcriptome*

Substances

  • Cholesterol Esters