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

Abstract

Background 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. Results 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. Conclusion 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.

Single‐cell RNA sequencing and lipidomics reveal cell and lipid dynamics of fat infiltration in skeletal muscle

“…However, the overall concentrations of lipid classes in GLY‐injected muscle were only affected marginally by cold exposure. The alteration patterns of fatty acyl chains associated with TAGs in GLY‐injected muscles resembled BAT more than white adipose tissue 20,21 . Marcher et al .…”

“…We hypothesized that by experimentally induced cold exposure, a shifting of intramuscular adipocytes towards a brown phenotype may be functionally related to some improvements in systemic metabolism. Cold exposure has been reported to be an efficient method to induce energy expenditure by activating UCP1 and influencing the dynamics of lipid metabolism and transcriptional processes in brown and white adipose tissue 20,21 . However, lipidomic alteration and its regulatory mechanism in the adipocyte‐infiltrated skeletal muscle remain unclear.…”

Integrated Pathways of COX-2 and mTOR: Roles in Cell Sensing and Alzheimer’s Disease

“…Nevertheless, there have been a few studies which have shown that inactivation of mTORC1 also compromises thermogenesis (D. Liu et al, 2016;Tran et al, 2016). While exposure to cold is also known to induce browning effect in mammals, it has been found to modify pathways involved in AD in a study carried out in mice models (Xu et al, 2019). Since mTOR and COX-2 have been found to operate together directly or indirectly in various other disorders or conditions, it can also be speculated that they may affect each other in this particular case.…”

“…Epidemiological studies have linked diabetes and obesity with dementia ( Ferreira et al, 2018 ). In fact, a lot of recent studies have highlighted the common cellular pathways underlying both diabetes and AD, thereby coining the term “type-3-diabetes” or “brain diabetes” to refer to AD ( Xu et al, 2019 ). Anti-diabetic drugs are being explored as potential candidates of anti-AD therapy ( De Felice, 2013 ).…”

SCD1 promotes lipid mobilization in subcutaneous white adipose tissue

“…Cold exposure induces beige fat biogenesis in subcutaneous white adipose tissue (scWAT) depots, promotes energy expenditure, and decreases mice body weight and fat mass (5). During cold exposure, β3-adrenergic receptor (β3AR) is activated by catecholamines released from sympathetic nerve.…”