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Beige adipose tissue has been considered to have potential applications in combating obesity and its related metabolic diseases. However, the mechanisms of acute cold-stimulated beige formation still remain largely unknown. Here, transcriptional analysis of acute cold-stimulated (4 °C for 4 h) subcutaneous white adipose tissue (sWAT) was conducted to determine the molecular signatures that might be involved in beige formation. Histological analysis confirmed the appearance of beige adipocytes in acute cold-treated sWAT. The RNA-sequencing data revealed that 714 genes were differentially expressed (p-value < 0.05 and fold change > 2), in which 221 genes were upregulated and 493 genes were downregulated. Gene Ontology (GO) analyses showed that the upregulated genes were enriched in the GO terms related to lipid metabolic process, fatty acid metabolic process, lipid oxidation, fatty acid oxidation, etc. In contrast, downregulated genes were assigned the GO terms of regulation of immune response, regulation of response to stimulus, defense response, etc. The expressions of some browning candidate genes were validated in cold-treated sWAT and 3T3-L1 cell browning differentiation. In summary, our results illustrated the transcriptional response of sWAT to acute cold exposure and identified the genes, including Acad11, Cyp2e1, Plin5, and Pdk2, involved in beige adipocyte formation in mice. [ABSTRACT FROM AUTHOR]

Uncoupling protein 1 (UCP1) plays a key role in nonshivering thermogenesis and is involved in the pathogenesis of obesity. In a previous study, we generated adipocyte-specific UCP1 knock-in (UCP1 -KI) pigs, which exhibited improved thermoregulatory ability and decreased fat deposition. To investigate whether UCP1 knock-in alters the lipid composition of adipose tissues, lipidomics of inguinal subcutaneous white adipose tissue (iWAT) and backfat from 6-month-old cold-treated UCP1 -KI pigs and wild-type (WT) pigs were profiled. In addition, genome-wide RNA-sequencing of iWAT was performed to further study the genetic basis for lipid alterations. The results showed that iWAT and backfat from UCP1- KI pigs exhibited distinct lipidomic profiles, as the mild lipid alteration was observed in backfat of UCP1 knock-in pigs. Inguinal WAT from UCP1 -KI pigs contained significantly decreased total triacylglycerol (p < 0.05), together with the downregulation of genes involved in fatty acid metabolism, suggesting the decreased lipogenesis in iWAT of UCP1 -KI pigs. Significantly increased levels of total sphingolipids (p <0.05) were also observed in iWAT from UCP1 -KI pigs. Notably, two mitochondrial-specific lipid species, cardiolipin CL72:8 (18:2) and CL74:9 (18:2), were found to be dramatically increased in iWAT from UCP1 -KI pigs, suggesting enhanced mitochondrial function. This observation was further supported by the significant upregulation of numerous mitochondrial-related genes and significantly increased number of large mitochondria and mitochondrial cristae in iWAT of UCP1 -KI pigs. Taken together, these data illustrate the specific role of UCP1 in lipid metabolism of fat tissues in pigs and provide new data for characterization of fat traits in UCP1 -KI pigs. • Inguinal subcutaneous white adipose tissue (iWAT) and backfat from UCP1- KI pigs exhibited distinct lipidomic profiles. • Significant reductions of total TAG in iWAT from UCP1 -KI pigs, together with the significantly downregulated fatty acid metabolism related genes, indicate the decreased lipid synthesis in iWAT of UCP1 -KI pigs. • Mitochondrial function was enhanced in iWAT of UCP1 -KI pigs, as evidenced by the significantly increased cardiolipin levels, upregulated numerous mitochondrial genes, increased number of large mitochondria and mitochondrial cristae density. [ABSTRACT FROM AUTHOR]