A non-cell autonomous mechanism of beige adipocyte renaissance in subcutaneous adipose tissue

Two types of UCP1 positive cells-brown and beige adipocytes exist in mammals. Beige adipocytes are very plastic, and can be dynamically regulated by environment.Beige adipocytes formed postnatally in subcutaneous inguinal white adipose tissue (iWAT) lost thermogenic gene expression and multilocular morphology at adult stage, but cold could restore their “beigeing” characteristics, a phenomenon termed as beige adipocyte renaissance. Our results showed that beige cell maintenance and renaissance in adult mice were regulated by cAMP and HDAC4 signaling in white adipocytes non-cell autonomously. Genetic modulations of various components of this cAMP-HDAC4 cascade (e.g. LKB1) led to persistent browning and reduced adiposity independent of thermogenesis. To further study the mechanisms of beige adipocytes maintenance, we performed RNA-seq with samples from inguinal white adipose tissues of WT, AdipoqCre LKB1 F/F, and AdipoqCre LKB1 F/F; HDAC4 F/F mice.Our studies will move the beige adipocyte field forward and attract clinical applications to target beige adipocyte renaissance. Overall design: Samples were divided into 3 groups: inguinal white adipose tissues from WT, AdipoqCre LKB1 F/F, and AdipoqCre LKB1 F/F; HDAC4 F/F mice. 5 mice/group. cDNA libraries were prepared using Ovation RNA-seq Systems V2 and Ovation Ultralow Library Systems V2 (Nugen) and subjected to sequencing using HiSeq 2500 System (Illumina).

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Wang Y, Paulo E, Wu D, Wu Y, Huang W, Chawla A, Wang B