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Single-cell transcriptome of stromal vascular fraction isolated from adipose tissue of lean and obese mice

ABSTRACT: Visceral white adipose tissue (VAT) is susceptible to inflammation as a result of obesity, and this inflammation contributes to the development of obesity-related diseases. During the development of obesity, inflammatory immunocytes, including CD8+ T cells, Th1 cells, M1-like macrophages, neutrophils, and mast cells, accumulate in VAT. While these profound changes in the immunocyte composition of VAT lead to local inflammation, the triggers of VAT inflammation remain poorly understood. Therefore, a better understanding of the mechanisms underlying an early event of obesity-associated VAT inflammation will contribute to the development of novel therapies for obesity-related diseases. We utilized CellChat, which employs the expression of ligand-receptor pairs as indicators of intercellular communications, to examine the potential impact of these identified cell types within SVF on T cells. Our analysis revealed that ASCs exert the greatest influence on T cells in both lean and obese conditions. Finally, we demonstrated that ASCs promote Tcell infiltration into WAT during the early stages of obesity.

ORGANISM(S): Mus musculus

PROVIDER: GSE237143 | GEO | 2023/10/01

REPOSITORIES: GEO

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Project description:Abstract: Background: The severity of visceral adipose tissue (VAT) inflammation in individuals with obesity is thought to signify obesity sub-phenotype(s) associated with higher cardiometabolic risk. Yet, this tissue is not accessible for direct sampling in the non-surgical patient. We hypothesized that circulating miRNAs (circ-miRs) could serve as biomarkers to distinguish human obesity subgroups with high or low extent of VAT-inflammation. Methods: Discovery and validation cohorts of patients living with obesity undergoing bariatric surgery (n=35 and 51, respectively) were included. VAT inflammation was classified into low/high based on an expression score derived from the mRNA levels of TNFA, IL6 and CCL2 (determined by rtPCR). Differentially-expressed circ-miRs were identified, and their discriminative power to detect low/high VAT inflammation was assessed by ROC-AUC analysis. Results: Fifty three out of 263 circ-miRs (20%) were associated with high VAT inflammation according to Mann-Whitney analysis in the discovery cohort. Of those, 12 (12/53=23%) were differentially expressed according to Deseq2, and 6 significantly discriminated between high and low VAT inflammation with ROC-AUC>0.8. Of the resulting 5 circ-miRs that were differentially abundant in all three statistical approaches, 3 were unaffected by hemolysis and validated in an independent cohort. Circ-miRs 181b-5p, 1306-3p, and 3138 combined with HOMA-IR exhibited ROC-AUC of 0.951 (95%CI:0.865-1) and 0.808 (95%CI:0.654-0.963) in the discovery and validation cohorts, respectively, providing strong discriminative power between participants with low versus high VAT inflammation. Predicted target genes of these miRNAs are enriched in pathways of insulin and inflammatory signaling, circadian entrainment, and cellular senescence. Conclusions: Circ-miRs that identify patients with low versus high VAT inflammation constitute a putative tool to improve personalized care of patients with obesity.

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Single-cell transcriptome of stromal vascular fraction isolated from adipose tissue of lean and obese mice

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