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Accumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice
- Source :
- Nature Communications, Nature Communications, Vol 13, Iss 1, Pp 1-12 (2022), Nature communications, vol 13, iss 1
- Publication Year :
- 2021
-
Abstract
- Various microbial products leaked from gut lumen exacerbate tissue inflammation and metabolic disorders in obesity. Vsig4+ macrophages are key players preventing infiltration of bacteria and their products into host tissues. However, roles of islet Vsig4+ macrophages in the communication between microbiota and β cells in pathogenesis of obesity-associated islet abnormalities are unknown. Here, we find that bacterial DNAs are enriched in β cells of individuals with obesity. Intestinal microbial DNA-containing extracellular vesicles (mEVs) readily pass through obese gut barrier and deliver microbial DNAs into β cells, resulting in elevated inflammation and impaired insulin secretion by triggering cGAS/STING activation. Vsig4+ macrophages prevent mEV infiltration into β cells through a C3-dependent opsonization, whereas loss of Vsig4 leads to microbial DNA enrichment in β cells after mEV treatment. Removal of microbial DNAs blunts mEV effects. Loss of Vsig4+ macrophages leads to microbial DNA accumulation in β cells and subsequently obesity-associated islet abnormalities.<br />Obesity is associated with increased gut permeability, and microbial products that are leaked from the gut may contribute towards obesity-associated inflammation. Here the authors show that the leakage of gut extracellular vesicles containing microbial DNA leads to bacterial DNA accumulation in pancreatic β-cells, promoting obesity-associated islet inflammation.
- Subjects :
- DNA, Bacterial
Knockout
Science
Complement
General Physics and Astronomy
Mice, Transgenic
Inbred C57BL
Diet, High-Fat
digestive system
General Biochemistry, Genetics and Molecular Biology
Transgenic
Oral and gastrointestinal
Article
Vaccine Related
Mice
Extracellular Vesicles
Islets of Langerhans
Insulin-Secreting Cells
Receptors
Insulin Secretion
2.1 Biological and endogenous factors
Animals
Humans
Obesity
Aetiology
Metabolic and endocrine
Monocytes and macrophages
Nutrition
Cancer
Inflammation
Mice, Knockout
Multidisciplinary
Prevention
Macrophages
digestive, oral, and skin physiology
Diabetes
Bacterial
Membrane Proteins
Metabolic diseases
General Chemistry
DNA
Nucleotidyltransferases
Diet
Gastrointestinal Microbiome
Receptors, Complement
Mice, Inbred C57BL
High-Fat
Signal Transduction
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 13
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....9d80dc22f010806bd729e0903bd7df75