Bone marrow mesenchymal stem cell‐derived exosomes reduce insulin resistance and obesity in mice via the PI3K/AKT signaling pathway

Obesity is a common chronic metabolic disease that induces chronic systemic inflammation in the body, eventually leading to related complications such as insulin resistance (IR), type 2 diabetes mellitus, and metabolic syndromes such as cardiovascular disease. Exosomes transfer bioactive substances...

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Main Authors: Hongwei Shi, Xiaojing Hao, Yaqin Sun, Huilin Zhang, Yating Zhao, Bin Wang, Jiayin Lu, Wei Hou, Yi Yan, Xiuju Yu, Linli Xue, Xiaomao Luo, Haidong Wang
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.13615
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author Hongwei Shi
Xiaojing Hao
Yaqin Sun
Huilin Zhang
Yating Zhao
Bin Wang
Jiayin Lu
Wei Hou
Yi Yan
Xiuju Yu
Linli Xue
Xiaomao Luo
Haidong Wang
author_facet Hongwei Shi
Xiaojing Hao
Yaqin Sun
Huilin Zhang
Yating Zhao
Bin Wang
Jiayin Lu
Wei Hou
Yi Yan
Xiuju Yu
Linli Xue
Xiaomao Luo
Haidong Wang
author_sort Hongwei Shi
collection DOAJ
description Obesity is a common chronic metabolic disease that induces chronic systemic inflammation in the body, eventually leading to related complications such as insulin resistance (IR), type 2 diabetes mellitus, and metabolic syndromes such as cardiovascular disease. Exosomes transfer bioactive substances to neighboring or distal cells through autosomal, paracrine, or distant secretion, regulating the gene and protein expression levels of receptor cells. In this study, we investigated the effect of mouse bone marrow mesenchymal stem cell‐derived exosomes (BMSC‐Exos) on high‐fat diet obese mice and mature 3T3‐L1 adipocyte models of IR. BMSC‐Exo treatment of obese mice promoted their metabolic homeostasis, including reduction of obesity, inhibition of M1‐type proinflammatory factor expression, and improvement of insulin sensitivity. In vitro analysis revealed that BMSC‐Exos improved IR and lipid droplet accumulation in mature 3T3‐L1 adipocytes treated with palmitate (PA). Mechanistically, BMSC‐Exos cause increased glucose uptake and improved IR in high‐fat chow‐fed mice and PA‐acting 3T3‐L1 adipocytes by activating the phosphoinositide 3‐kinases/protein kinase B (PI3K/AKT) signaling pathway and upregulating glucose transporter protein 4 (GLUT4) expression. This study offers a new perspective for the development of treatments for IR in obese and diabetic patients.
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spelling doaj.art-c04f3fb0b95d42d6bd854d06fdf1336d2023-06-05T08:21:04ZengWileyFEBS Open Bio2211-54632023-06-011361015102610.1002/2211-5463.13615Bone marrow mesenchymal stem cell‐derived exosomes reduce insulin resistance and obesity in mice via the PI3K/AKT signaling pathwayHongwei Shi0Xiaojing Hao1Yaqin Sun2Huilin Zhang3Yating Zhao4Bin Wang5Jiayin Lu6Wei Hou7Yi Yan8Xiuju Yu9Linli Xue10Xiaomao Luo11Haidong Wang12College of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaCollege of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaCollege of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaCollege of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaCollege of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaCollege of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaCollege of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaCollege of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaCollege of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaCollege of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaCollege of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaCollege of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaCollege of Veterinary Medicine Shanxi Agricultural University Jinzhong ChinaObesity is a common chronic metabolic disease that induces chronic systemic inflammation in the body, eventually leading to related complications such as insulin resistance (IR), type 2 diabetes mellitus, and metabolic syndromes such as cardiovascular disease. Exosomes transfer bioactive substances to neighboring or distal cells through autosomal, paracrine, or distant secretion, regulating the gene and protein expression levels of receptor cells. In this study, we investigated the effect of mouse bone marrow mesenchymal stem cell‐derived exosomes (BMSC‐Exos) on high‐fat diet obese mice and mature 3T3‐L1 adipocyte models of IR. BMSC‐Exo treatment of obese mice promoted their metabolic homeostasis, including reduction of obesity, inhibition of M1‐type proinflammatory factor expression, and improvement of insulin sensitivity. In vitro analysis revealed that BMSC‐Exos improved IR and lipid droplet accumulation in mature 3T3‐L1 adipocytes treated with palmitate (PA). Mechanistically, BMSC‐Exos cause increased glucose uptake and improved IR in high‐fat chow‐fed mice and PA‐acting 3T3‐L1 adipocytes by activating the phosphoinositide 3‐kinases/protein kinase B (PI3K/AKT) signaling pathway and upregulating glucose transporter protein 4 (GLUT4) expression. This study offers a new perspective for the development of treatments for IR in obese and diabetic patients.https://doi.org/10.1002/2211-5463.13615BMSCexosomesinflammationinsulin resistanceobesityPI3K/AKT
spellingShingle Hongwei Shi
Xiaojing Hao
Yaqin Sun
Huilin Zhang
Yating Zhao
Bin Wang
Jiayin Lu
Wei Hou
Yi Yan
Xiuju Yu
Linli Xue
Xiaomao Luo
Haidong Wang
Bone marrow mesenchymal stem cell‐derived exosomes reduce insulin resistance and obesity in mice via the PI3K/AKT signaling pathway
FEBS Open Bio
BMSC
exosomes
inflammation
insulin resistance
obesity
PI3K/AKT
title Bone marrow mesenchymal stem cell‐derived exosomes reduce insulin resistance and obesity in mice via the PI3K/AKT signaling pathway
title_full Bone marrow mesenchymal stem cell‐derived exosomes reduce insulin resistance and obesity in mice via the PI3K/AKT signaling pathway
title_fullStr Bone marrow mesenchymal stem cell‐derived exosomes reduce insulin resistance and obesity in mice via the PI3K/AKT signaling pathway
title_full_unstemmed Bone marrow mesenchymal stem cell‐derived exosomes reduce insulin resistance and obesity in mice via the PI3K/AKT signaling pathway
title_short Bone marrow mesenchymal stem cell‐derived exosomes reduce insulin resistance and obesity in mice via the PI3K/AKT signaling pathway
title_sort bone marrow mesenchymal stem cell derived exosomes reduce insulin resistance and obesity in mice via the pi3k akt signaling pathway
topic BMSC
exosomes
inflammation
insulin resistance
obesity
PI3K/AKT
url https://doi.org/10.1002/2211-5463.13615
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