RNA-Seq and Mass-Spectrometry-Based Lipidomics Reveal Extensive Changes of Glycerolipid Pathways in Brown Adipose Tissue in Response to Cold

• This study integrates transcriptome/lipidome analysis of BAT in cold-exposed mice
• Cold exposure induces glycerolipid gene programs
• Long-chain and odd-numbered acyl chains in TAGs are increased in response to cold
• Glycerophospholipid species are differentially remodeled in response to cold

SummaryCold exposure greatly alters brown adipose tissue (BAT) gene expression and metabolism to increase thermogenic capacity. Here, we used RNA sequencing and mass-spectrometry-based lipidomics to provide a comprehensive resource describing the molecular signature of cold adaptation at the level of the transcriptome and lipidome. We show that short-term (3-day) cold exposure leads to a robust increase in expression of several brown adipocyte genes related to thermogenesis as well as the gene encoding the hormone irisin. However, pathway analysis shows that the most significantly induced genes are those involved in glycerophospholipid synthesis and fatty acid elongation. This is accompanied by significant changes in the acyl chain composition of triacylglycerols (TAGs) as well as subspecies-selective changes of acyl chains in glycerophospholipids. These results indicate that cold adaptation of BAT is associated with significant and highly species-selective remodeling of both TAGs and glycerophospholipids.

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