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Integrated Analysis of lncRNA and mRNA Expression Profiles in brown adipose tissue of obesity-prone and obesity-resistant mice

ABSTRACT: Integrated Analysis of lncRNA and mRNA Expression Profiles in brown adipose tissue of obesity-prone and obesity-resistant mice

PROVIDER: PRJNA853392 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19879201.fastq.gz	Fastqsanger.gz
	SRR19879202.fastq.gz	Fastqsanger.gz
	SRR19879203.fastq.gz	Fastqsanger.gz
	SRR19879204.fastq.gz	Fastqsanger.gz
	SRR19879205.fastq.gz	Fastqsanger.gz

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LncRNA and mRNA expression profiles in brown adipose tissue of obesity-prone and obesity-resistant mice.

Project description:Obesity-prone or obesity-resistant phenotypes can exist in individuals who consume the same diet type. Brown adipose tissue functions to dissipate energy in response to cold exposure or overfeeding. Long noncoding RNAs play important roles in a wide range of biological processes. However, systematic examination of lncRNAs in phenotypically divergent mice has not yet been reported. Here, the lncRNA expression profiles in BAT of HFD-induced C57BL/6J mice were investigated by high-throughput RNA sequencing. Genes that play roles in thermogenesis and related pathways were identified. We found lncRNA (Gm44502) may play a thermogenic role in obesity resistance by interacting with six mRNAs. Our results also indicated that seven differentially expressed lncRNAs (4930528G23Rik, Gm39490, Gm5627, Gm15551, Gm16083, Gm36860, Gm42002) may play roles in reducing heat production in obesity susceptibility by interacting with seven differentially expressed mRNAs. The screened lncRNAs may participate in the pathogenesis of weight regulation and provide insight into obesity therapy.

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Project description:The expression profiles of lncRNAs in BAT were investigated by high-throughput RNA sequencing using HFD-induced C57BL/6J mice. Genes that play roles in thermogenesis and related pathways were identified.

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Project description:Brown adipose tissue (BAT) is considered as a main site of adaptive thermogenesis and the thermogenic activities of brown and beige adipocytes are also linked to generating heat and counteracting obesity. Recent studies revealed that BAT could secrete certain batokines-like factors especially small extracellular vesicles (sEV), which contributed to the systemic consequences of BAT activities. As a newly emerging class of mediators, some long non-coding RNAs (lncRNAs) have exhibited metabolic regulatory effects in adipocyte development. However, besides the well-studied lncRNAs, the lncRNAs carried by sEV derived from brown adipose tissue (sEV-BAT) have not been characterized yet. In this study, we conducted a lncRNA microarray assay on sEV-WAT and sEV-BAT. A total of 563 types of known lncRNAs were identified to be differentially expressed, among which 232 lncRNAs were upregulated and 331 lncRNAs were downregulated in sEV-BAT. Three novel candidates (AK029592, humanlincRNA1030 and ENSMUST00000152284) were selected for further validation. LncRNA–mRNA network analysis revealed candidate lncRNAs were largely embedded in cellular metabolic pathways. During adipogenic and thermogenic phenotype differentiation in ASCs and 3T3-L1 cells, only the expressions of AK029592 were upregulated. The three lncRNAs were all relatively enriched in brown adipose tissues and brown adipocytes. In different adipocytes, sEV and adipose tissue, the expression of AK029592 and ENSMUST00000152284 were significantly decreased in obese mice compared to lean controls, while obesity could not alter the expression of humanlincRNA1030.

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Project description:Multi-omics Reveals Different Signatures of Obesity-Prone and Obesity-Resistant Mice

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Paternal cold exposure enhances brown adipose tissue sensitivity in offspring and ameliorates diet induced obesity

Project description:Research in recent years has focused on environmental effects that control tissue functionality and systemic metabolism. We show here in a retrospective analysis that presence of brown adipocytes and date of birth are correlated and linked to BMI. In a mouse model system, we demonstrate that pre-conception cold exposure leads to improved systemic metabolism and protects from diet induced obesity, through the sperm via the paternal lineage. Using a brown fat ablation model, we show that this effect is mediated by brown adipose tissue. Furthermore, through RNAseq and DNA methylation analysis we identify Adrb3 as a putative signaling mechanism which could mediate the effects of pre-conception cold exposure and could account for the heterogeneity of brown adipose tissue responsiveness. Taken together, our results identify paternal cold exposure as a stimulus which induces a hyper-active state in brown adipose tissue leading to improved adaptation to overnutrition and hypothermia in the offspring.

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