Brown adipose tissue (BAT) plays an important role in maintain body temperature, treating obesity and diabetes. However, the amount and activity of BAT in adults (a-BAT) is very low, while the BAT in infant (i-BAT) is abundant and with strong activation. The a-BAT and i-BAT vary greatly in activation, but the characteristics and differences at the molecular level have not yet been fully revealed. We examined the changes in the mRNA expression of UCP1 and thermogenic genes genes such as PRDM16, PGC1α, CPT1α and CPT1β in a-BAT and i-BAT of mouse. We found that, compared with i-BAT, both UCP1 and thermogenic genes were significantly decreased in a-BAT. Western blot data further confirmed the result. Transmission electron microscope (TEM) and scanning electron microscopy (SEM) also showed a clear distinction in a-BAT and i-BAT. Compared with a-BAT, the lipid droplet is less and mitochondrial density is higher in i-BAT. In addition, the characteristics and differences of a-BAT and i-BAT were comprehensively analyzed by mRNA, microRNA, LncRNA, circRNA, DNA methylation and proteome. Thousands of signifcantly changed lncRNAs and mRNAs as well as proteins were identifed. Compared with i-BAT, we found hyper 383 and hypo 503 DMR related genes in a-BAT by differentially methylated region (DMR) analysis. What’s more, we found 1221 new circRNA in i-BAT and 1991 new circRNA in a-BAT and there were significant higher expression of circRNA in a-BAT compared with i-BAT. Furthermore, we constructed correlated expression networks circRNA-mRNA-lncRNA-methylation with bioinformatics methods. Co-expression analysis showed lnc-NONMMUG024827 and lnc-NONMMUG020075 expression is correlated with Fatty acid metabolism genes, including FASN and ACADA. Taken together, these results provide a better understanding of BAT function and development, and show a novel perspective roles of i-BAT or making a-BAT achieve the better activation and dynamic state just like i-BAT through the epigenetic modification.

Disclosure

C. Zhang: None. R. Yin: None. Y. Sheng: None. C. Yang: None. X. He: None. W. Xu: None. K. Huang: None.

© 2018 by the American Diabetes Association.
2018
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