Abstract
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.
Highlights
Obesity, a condition of excess fat accumulates in the body, and its related metabolic diseases, such as cardiovascular disease and diabetes, have become global health issues [1,2]
brown adipose tissue (BAT) plays a critical role in adaptive thermogenesis and influences glucose and lipid metabolism due to its high mitochondrial content and high expression of uncoupling protein 1 (UCP1) [3]
A new kind of adipocyte was identified in white adipose tissue (WAT) upon various environmental cues, such as chronic cold stimulation, exercise, and treatment with rosiglitazone, the agonist of the major regulator of adipogenesis, peroxisome proliferator-activated receptor-γ (PPARγ) [3,4]
Summary
A condition of excess fat accumulates in the body, and its related metabolic diseases, such as cardiovascular disease and diabetes, have become global health issues [1,2]. The expression of genes involved in the regulation of immune response (Tnfrsf13c, Cd48, Ighd, etc.), regulation of response to stimulus (Npas, Bank, Gpr183, etc.), cell adhesion (Ncan, Sell, Egr, etc.), and defense response (Hck, Blk, Ccr, etc.) was significantly downregulated in sWAT from cold-treated mice (Supplementary Figure S1A). Our data revealed 221 significantly upregulated genes that were enriched in the GO annotations of lipid metabolic process, fatty acid metabolic process, lipid oxidation, fatty acid oxidation, and the PPAR signaling pathway These enriched GO terms were quite similar to the terms identified for DEGs in the inguinal WAT of chronic cold-treated (6 ◦C for 10 days) 129Sv mice [15]. Further investigation of the roles of these genes in beige adipocyte formation will explore the possibility of therapeutic targets for obesity and its related metabolic diseases
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