Endothelial Angpt2 Promotes Adipocyte Progenitor Cells Maturation to Increase Visceral Adipose Tissue Accumulation

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes/Metabolism Research and Reviews Pub Date : 2024-12-03 DOI:10.1002/dmrr.70012

Xianhao Yi, Jiapu Ling, Yan Tang, Jingjing Cai, Shaihong Zhu, Liyong Zhu

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引用次数: 0

Abstract

Aims

Visceral adipose tissue (VAT) accumulation is essential for the occurrence and development of obesity and related metabolic diseases. Currently, the specific mechanism of VAT accumulation is still unclear.

Materials and Methods

We searched the Gene Expression Omnibus database to obtain single-cell RNA sequencing (scRNAseq) data for VAT in patients with a normal body mass index (BMI), obesity, or morbid obesity. By using PCR, WB, immunofluorescence staining, and flow cytometry analysis, we validated the interactions between macrophages, endothelial cells (ECs), and adipocyte progenitor cells (APCs), as well as the underlying mechanism, in VAT. Finally, we tested the findings in obese mice using recombinant proteins and adeno-associated virus infection.

Results

One study with human scRNAseq data was included. This study collected 13-VAT from 5 individuals with obesity and diabetes, 9 individuals with obesity, and 1 individual with a normal BMI. The proportion of inflammatory macrophages is substantially increased in obese and diabetic patients. ECs have the most active interactions with other cells. Notably, the activation of JAK1/STAT3 is one of the reasons for the increase in inflammatory endothelial cells and can promote the secretion of angiopoietin-2 (Angpt2) and induce APCs to transition from mesothelin (MSLN) to complement factor D (CFD) expression via integrin-α5β1 signalling. This phenotypic transition promotes APC differentiation into mature adipocytes and accelerates VAT accumulation. These observations were further validated in an in vitro model and an in vivo study using Angpt2 recombinant proteins and blocking the expression of Angpt2 by adeno-associated virus infection.

Conclusions

ECs are essential for promoting VAT accumulation by facilitating APC differentiation from MSLN to CFD phenotype. This process is driven by Angpt2 from ECs upon JAK1/STAT3 signalling activation under metabolic stress.

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来源期刊

Diabetes/Metabolism Research and Reviews 医学-内分泌学与代谢

CiteScore

17.20

自引率

2.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Diabetes/Metabolism Research and Reviews is a premier endocrinology and metabolism journal esteemed by clinicians and researchers alike. Encompassing a wide spectrum of topics including diabetes, endocrinology, metabolism, and obesity, the journal eagerly accepts submissions ranging from clinical studies to basic and translational research, as well as reviews exploring historical progress, controversial issues, and prominent opinions in the field. Join us in advancing knowledge and understanding in the realm of diabetes and metabolism.