Cold-induced lipid dynamics and transcriptional programs in white adipose tissue

In mammals, cold exposure induces browning of white adipose tissue (WAT) and alters WAT gene expression and lipid metabolism to boost adaptive thermogenesis and maintain body temperature. Understanding the lipidomic and transcriptomic profiles of WAT upon cold exposure provides insights into the adaptive changes associated with this process. Here, we applied mass spectrometry and RNA sequencing (RNA-seq) to provide a comprehensive resource for describing the lipidomic or transcriptome profiles in cold-induced inguinal WAT (iWAT). We showed that short-term (3-day) cold exposure induces browning of iWAT, increases energy expenditure, and results in loss of body weight and fat mass. Lipidomic analysis shows that short-term cold exposure leads to dramatic changes of the overall composition of lipid classes WAT. Notably, cold exposure induces significant changes in the acyl-chain composition of triacylglycerols (TAGs), as well as the levels of glycerophospholipids and sphingolipids in iWAT. RNA-seq and qPCR analysis suggests that short-term cold exposure alters the expression of genes and pathways involved in fatty acid elongation, and the synthesis of TAGs, sphingolipids, and glycerophospholipids. Furthermore, the cold-induced lipid dynamics and gene expression pathways in iWAT are contrary to those previously observed in metabolic syndrome, neurodegenerative disorders, and aging, suggesting beneficial effects of cold-induced WAT browning on health and lifespan. We described the significant alterations in the composition of glyphospholipids, glycerolipids, and sphingolipids and expression of genes involved in thermogenesis, fatty acid elongation, and fatty acid metabolism during the response of iWAT to short-term cold exposure. We also found that some changes in the levels of specific lipid species happening after cold treatment of iWAT are negatively correlated to metabolic diseases, including obesity and T2D.