Comparative Transcriptome and Lipidome Analyses Suggest a Lipid Droplet-Specific Response to Heat Exposure of Brown Adipose Tissue in Normal and Obese Mice

Abstract

AimsIn 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, 4h) 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.

Note:
Funding Information: This work was supported by the National Key Research and Development Program of China (No. 2021YFF1000601), the National Natural Science Foundation of China (32172700) and the Joint Funds of the National Natural Science Foundation of China (U20A2052).

Declaration of Interests: The authors declare that they have no conflict of interest.

Ethics Approval Statement: Animal’s care and sample collection in this study were carried out in accordance with the pre-approved guidelines from Regulation Proclamation No.5 of the Standing Committee of Hubei People’s Congress, and all experimental procedures were approved by the Institutional Animal Care and Use Committee of Huazhong Agricultural University, Wuhan, China (HZAUSW-2016-015).

Keywords: heat exposure, iBAT, obesity, lipid droplets, RNA sequencing, lipidomics