Nat Commun: Scientists Find Obesity Induces Islet Inflammation!

As a marker of obesity, low-grade tissue inflammation is manifested in various organs such as adipose tissue, liver, muscle, and pancreatic islets
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Chronic islet inflammation exists in both obese mouse models of type 2 diabetes (T2DM) and obese/T2DM patients
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This obesity-induced islet inflammation can lead to the β-cell abnormalities characteristic of T2DM
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Leakage of various microbial products from the gut has been shown to exacerbate tissue inflammation and metabolic disturbances in obese patients
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Vsig4+ macrophages are key to preventing the infiltration of bacteria and their products into host tissues
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However, the regulatory role of islet Vsig4+ macrophages between the microbiota and β cells in the pathogenesis of obesity-related islet abnormalities remains unclear
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A research paper titled "Accumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice" published on Nat Commun specifically elucidates this mechanism
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The researchers first used 16s rRNA probes to detect the abundance of bacterial DNA in the pancreas of healthy individuals or obese/T2DM patients and found that bacterial DNA was enriched in pancreatic beta cells of obese hosts; in addition, in the case of obesity, microbial DNA was contained The extracellular vesicles (mEVs) can reach the host pancreas through the intestinal barrier
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The researchers analyzed the important role of Vsig4+ macrophages in preventing islet mEV infiltration and found that Vsig4+ macrophages prevented islet infiltration of intestinal mEVs
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Since microbial-derived products can exacerbate tissue inflammation and metabolic disturbances in obese patients, we assessed whether accumulation of bacterial DNA triggers islet inflammation and beta-cell dysfunction, and investigated the effect of obese mEVs on triggering islet inflammation and beta-cell abnormalities.
We found that microbial-derived EVs contribute to obesity-related islet inflammation and β-cell abnormalities, and that obese mEVs can trigger islet inflammation and β-cell dysfunction in the absence of Vsig4+ macrophages
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In addition, they assessed whether islet Vsig4+ macrophages can effectively protect islets from the pathogenic effects of intestinal mEV in the absence of liver Vsig4+ macrophages, and the results show that islet Vsig4+ macrophages are sufficient to block intestinal mEV pathogenic effect
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In addition, the researchers also found that microbial DNA is a key pathogenic vector for islet dysfunction in intestinal EVs in obese patients
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Microbial DNA promotes activation of the cGAS/STING pathway and triggers islet inflammation; Vsig4+ macrophages prevent mEV infiltration into β cells through c3-dependent opsonization, while Vsig4 deletion results in enrichment of microbial DNA in β cells after mEV treatment
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Figure Obesity mEVs contribute to obesity-related islet inflammation and β-cell abnormalities

 

This study specifically elucidates the mechanism of action of islet Vsig4+ macrophages in preventing obesity-related islet inflammation and abnormal development of beta cells
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Reference: Gao, H.
, Luo, Z.
, Ji, Y.
et al.
Accumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice.
Nat Commun 13, 565 (2022).