De Novo Reconstruction of Transcriptome Identified Long Non-Coding RNA Regulator of Aging-Related Brown Adipose Tissue Whitening in Rabbits

SIMPLE SUMMARY: Brown adipose tissues (BATs) undergo the conversion to white adipose tissues (WATs) with age. Long non-coding RNAs (lncRNAs) were widely involved in adipose biology. Rabbit is an ideal model for studying the dynamics of the transformation from BATs to WATs. However, our knowledge of lncRNAs that mediate the transformation remains unknown in rabbits. By histological analysis and sequencing, we found rabbit interscapular adipose tissues (iATs) from BATs to WATs within two years and identified a total of 631 differentially expressed lncRNAs (DELs) during the transformation process. Several signal pathways were involved in the transformation from BAT to WAT. A novel lncRNA that was highly expressed in iATs of aged rabbits was validated to impair brown adipocyte differentiation in vitro. Our study provided a comprehensive catalog of lncRNAs involved in the transformation from BATs to WATs in rabbits, facilitating a better understanding of adipose biology. ABSTRACT: Brown adipose tissues (BATs) convert to a “white-like” phenotype with age, which is also known as “aging-related BAT whitening (ARBW)”. Emerging evidence suggested that long non-coding RNAs (lncRNAs) were widely involved in adipose biology. Rabbit is an ideal model for studying the dynamics of ARBW. In this study, we performed histological analysis and strand-specific RNA-sequencing (ssRNA-seq) of rabbit interscapular adipose tissues (iATs). Our data indicated that the rabbit iATs underwent the ARBW from 0 days to 2 years and a total of 2281 novel lncRNAs were identified in the iATs. The classical rabbit BATs showed low lncRNA transcriptional complexity compared to white adipose tissues (WATs). A total of 631 differentially expressed lncRNAs (DELs) were identified in four stages. The signal pathways of purine metabolism, Wnt signaling pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway, cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (cGMP-PKG) signaling pathway and lipid and atherosclerosis were significantly enriched by the DELs with unique expression patterns. A novel lncRNA that was highly expressed in the iATs of aged rabbits was validated to impair brown adipocyte differentiation in vitro. Our study provided a comprehensive catalog of lncRNAs involved in ARBW in rabbits, which facilitates a better understanding of adipose biology.