Dataset Information

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

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.

SUBMITTER: Du K

PROVIDER: S-EPMC8614855 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Du Kun K Bai Xue X Yang Li L Shi Yu Y Chen Li L Wang Haoding H Cai Mingchen M Wang Jie J Chen Shiyi S Jia Xianbo X Lai Songjia S

Biology 20211113 11

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 ...[more]

PMID: 34827171

Similar Datasets

Project description:BackgroundThe brown adipose tissue (BAT) is a target for treating obesity. BAT losses thermogenic capacity and gains a "white adipose tissue-like" phenotype ("BAT whitening") under thermoneutral environments, which is a potential factor causing a low curative effect in BAT-related obesity treatments. Circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNA) to mRNAs and function in various processes by sponging shared microRNAs (miRNAs). However, the roles of circRNA- and lncRNA-related ceRNA networks in regulating BAT whitening remain litter known.ResultsIn this study, BATs were collected from rabbits at day0 (D0), D15, D85, and 2 years (Y2). MiRNA-seq was performed to investigate miRNA changes during BAT whitening. Then, a combined analysis of circRNA-seq and whole-transcriptome sequencing was used for circRNA assembly and quantification during BAT whitening. Our data showed that 1187 miRNAs and 6204 circRNAs were expressed in the samples, and many of which were identified as significantly changed during BAT whitening. Target prediction showed that D0-selective miRNAs were significantly enriched in the Ras, MAPK, and PI3K-Akt signaling pathways, and Y2-selective miRNAs were predicted to be involved in cell proliferation. The cyclization of several circRNAs could form novel response elements of key thermogenesis miRNAs at the back-splicing junction (BSJ) sites, and in combination with a dual-luciferase reporter assay confirmed the binding between the BSJ site of novel_circ_0013792 and ocu-miR-378-5p. CircRNAs and lncRNAs have high cooperativity in sponging miRNAs during BAT whitening. Both circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA triple networks were significantly involved in immune response-associated biological processes. The D15-selective circRNA might promote BAT whitening by increasing the expression of IDH2. The Y2-selective circRNA-related ceRNA network and lncRNA-related ceRNA network might regulate the formation of the WAT-like phenotype of BAT via MAPK and Ras signaling pathways, respectively.ConclusionsOur work systematically revealed ceRNA networks during BAT whitening in rabbits and might provide new insight into BAT-based obesity treatments.

Project description:Brown adipose tissue (BAT) represents a valuable target for treating obesity in humans. BAT losses of thermogenic capacity and gains a "white adipose tissue-like (WAT-like)" phenotype (BAT whitening) under thermoneutral environments, which could lead to potential low therapy responsiveness in BAT-based obesity treatments. However, the epigenetic mechanisms of BAT whitening remain largely unknown. In this study, BATs were collected from rabbits at day0 (D0), D15, D85, and 2 years (Y2). RNA-sequencing (RNA-seq) and the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were performed to investigate transcriptome and chromatin accessibility of BATs at the four whitening stages, respectively. Our data showed that many genes and chromatin accessible regions (refer to as "peaks") were identified as significantly changed during BAT whitening in rabbits. The BAT-selective genes downregulated while WAT-selective genes upregulated from D0 to Y2, and the de novo lipogenesis-related genes reached the highest expression levels at D85. Both the highly expressed genes and accessible regions in Y2 were significantly enriched in immune response-related signal pathways. Analysis of different relationships between peaks and their nearby genes found an increased proportion of the synchronous changes between chromatin accessibility and gene expression during BAT whitening. The synergistic changes between the chromatin accessibility of promoter and the gene expression were found in the key adipose genes. The upregulated genes which contained increased peaks were significantly enriched in the PI3K-Akt signaling pathway, steroid biosynthesis, TGF-beta signaling pathway, osteoclast differentiation, and dilated cardiomyopathy. Moreover, the footprinting analysis suggested that sequential regulation of potential transcription factors (TFs) mediated the loss of thermogenic phenotype and the gain of a WAT-like phenotype of BAT. In conclusion, our study provided the transcriptional and epigenetic frameworks for understanding BAT whitening in rabbits for the first time and might facilitate potential insights into BAT-based obesity treatments.

Project description:ObjectiveBrown adipose tissue (BAT) thermogenesis offers the potential to improve metabolic health in mice and humans. However, humans predominantly live under thermoneutral conditions, leading to BAT whitening, a reduction in BAT mitochondrial content and metabolic activity. Recent studies have established mitophagy as a major driver of mitochondrial degradation in the whitening of thermogenic brite/beige adipocytes, yet the pathways mediating mitochondrial breakdown in whitening of classical BAT remain largely elusive. The transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy belonging to the MiT family of transcription factors, is the only member of this family that is upregulated during whitening, pointing toward a role of TFEB in whitening-associated mitochondrial breakdown.MethodsWe generated brown adipocyte-specific TFEB knockout mice, and induced BAT whitening by thermoneutral housing. We characterized gene and protein expression patterns, BAT metabolic activity, systemic metabolism, and mitochondrial localization using in vivo and in vitro approaches.ResultsUnder low thermogenic activation conditions, deletion of TFEB preserves mitochondrial mass independently of mitochondriogenesis in BAT and primary brown adipocytes. However, this does not translate into elevated thermogenic capacity or protection from diet-induced obesity. Autophagosomal/lysosomal marker levels are altered in TFEB-deficient BAT and primary adipocytes, and lysosomal markers co-localize and co-purify with mitochondria in TFEB-deficient BAT, indicating trapping of mitochondria in late stages of mitophagy.ConclusionWe identify TFEB as a driver of BAT whitening, mediating mitochondrial degradation via the autophagosomal and lysosomal machinery. This study provides proof of concept that interfering with the mitochondrial degradation machinery can increase mitochondrial mass in classical BAT under human-relevant conditions. However, it must be considered that interfering with autophagy may result in accumulation of non-functional mitochondria. Future studies targeting earlier steps of mitophagy or target recognition are therefore warranted.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets