Adipose Tissue Macrophages Modulate Obesity-Associated β Cell Adaptations through Secreted miRNA-Containing Extracellular Vesicles
Obesity induces an adaptive expansion of β cell mass and insulin secretion abnormality. Expansion of adipose tissue macrophages (ATMs) is a hallmark of obesity. Here, we assessed a novel role of ATMs in mediating obesity-induced β cell adaptation through the release of miRNA-containing extracellular...
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MDPI AG
2021-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/9/2451 |
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| author | Hong Gao Zhenlong Luo Zhongmou Jin Yudong Ji Wei Ying |
| author_facet | Hong Gao Zhenlong Luo Zhongmou Jin Yudong Ji Wei Ying |
| author_sort | Hong Gao |
| collection | DOAJ |
| description | Obesity induces an adaptive expansion of β cell mass and insulin secretion abnormality. Expansion of adipose tissue macrophages (ATMs) is a hallmark of obesity. Here, we assessed a novel role of ATMs in mediating obesity-induced β cell adaptation through the release of miRNA-containing extracellular vesicles (EVs). In both in vivo and in vitro experiments, we show that ATM EVs derived from obese mice notably suppress insulin secretion and enhance β cell proliferation. We also observed similar phenotypes from human islets after obese ATM EV treatment. Importantly, depletion of miRNAs blunts the effects of obese ATM EVs, as evidenced by minimal effects of obese DicerKO ATM EVs on β cell responses. miR-155 is a highly enriched miRNA within obese ATM EVs and miR-155 overexpressed in β cells impairs insulin secretion and enhances β cell proliferation. In contrast, knockout of miR-155 attenuates the regulation of obese ATM EVs on β cell responses. We further demonstrate that the miR-155-<i>Mafb</i> axis plays a critical role in controlling β cell responses. These studies show a novel mechanism by which ATM-derived EVs act as endocrine vehicles delivering miRNAs and subsequently mediating obesity-associated β cell adaptation and dysfunction. |
| first_indexed | 2024-03-10T07:48:22Z |
| format | Article |
| id | doaj.art-6a7d3c37068f44f4b856e4b3a2916e85 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T07:48:22Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-6a7d3c37068f44f4b856e4b3a2916e852023-11-22T12:26:25ZengMDPI AGCells2073-44092021-09-01109245110.3390/cells10092451Adipose Tissue Macrophages Modulate Obesity-Associated β Cell Adaptations through Secreted miRNA-Containing Extracellular VesiclesHong Gao0Zhenlong Luo1Zhongmou Jin2Yudong Ji3Wei Ying4Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA 92093, USADivision of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA 92093, USADivision of Biological Sciences, University of California, San Diego, CA 92093, USADivision of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA 92093, USADivision of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA 92093, USAObesity induces an adaptive expansion of β cell mass and insulin secretion abnormality. Expansion of adipose tissue macrophages (ATMs) is a hallmark of obesity. Here, we assessed a novel role of ATMs in mediating obesity-induced β cell adaptation through the release of miRNA-containing extracellular vesicles (EVs). In both in vivo and in vitro experiments, we show that ATM EVs derived from obese mice notably suppress insulin secretion and enhance β cell proliferation. We also observed similar phenotypes from human islets after obese ATM EV treatment. Importantly, depletion of miRNAs blunts the effects of obese ATM EVs, as evidenced by minimal effects of obese DicerKO ATM EVs on β cell responses. miR-155 is a highly enriched miRNA within obese ATM EVs and miR-155 overexpressed in β cells impairs insulin secretion and enhances β cell proliferation. In contrast, knockout of miR-155 attenuates the regulation of obese ATM EVs on β cell responses. We further demonstrate that the miR-155-<i>Mafb</i> axis plays a critical role in controlling β cell responses. These studies show a novel mechanism by which ATM-derived EVs act as endocrine vehicles delivering miRNAs and subsequently mediating obesity-associated β cell adaptation and dysfunction.https://www.mdpi.com/2073-4409/10/9/2451adipose tissue macrophageextracellular vesiclemiRNAβ cell replicationinsulin secretionobesity |
| spellingShingle | Hong Gao Zhenlong Luo Zhongmou Jin Yudong Ji Wei Ying Adipose Tissue Macrophages Modulate Obesity-Associated β Cell Adaptations through Secreted miRNA-Containing Extracellular Vesicles Cells adipose tissue macrophage extracellular vesicle miRNA β cell replication insulin secretion obesity |
| title | Adipose Tissue Macrophages Modulate Obesity-Associated β Cell Adaptations through Secreted miRNA-Containing Extracellular Vesicles |
| title_full | Adipose Tissue Macrophages Modulate Obesity-Associated β Cell Adaptations through Secreted miRNA-Containing Extracellular Vesicles |
| title_fullStr | Adipose Tissue Macrophages Modulate Obesity-Associated β Cell Adaptations through Secreted miRNA-Containing Extracellular Vesicles |
| title_full_unstemmed | Adipose Tissue Macrophages Modulate Obesity-Associated β Cell Adaptations through Secreted miRNA-Containing Extracellular Vesicles |
| title_short | Adipose Tissue Macrophages Modulate Obesity-Associated β Cell Adaptations through Secreted miRNA-Containing Extracellular Vesicles |
| title_sort | adipose tissue macrophages modulate obesity associated β cell adaptations through secreted mirna containing extracellular vesicles |
| topic | adipose tissue macrophage extracellular vesicle miRNA β cell replication insulin secretion obesity |
| url | https://www.mdpi.com/2073-4409/10/9/2451 |
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