Clec7a drives gut fungus-mediated host lipid deposition

BackgroundCompared to that of bacteria, the role of gut fungi in obesity development remains unknown.ResultsHere, alterations in gut fungal biodiversity and composition were confirmed in obese pig models and high-fat diet (HFD)-fed mice. Antifungal drugs improved diet-induced obesity, while fungal r...

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Published in:Microbiome 2023-11, Vol.11 (1), p.1-264, Article 264
Main Authors: Ma, Jie, Zhou, Miao, Song, Zehe, Deng, Yuankun, Xia, Siting, Li, Yunxia, Huang, Xingguo, Xiao, Dingfu, Yin, Yulong, Yin, Jie
Format: Article
Language:English
Subjects:
Adipocytes
Animal models
Antifungal agents
Bacteria
Biodiversity
Body fat
Clec7a
Diet
Dietary supplements
Fecal microflora
Feces
Fungi
Glucose
Gut fungi
High fat diet
Hogs
Immunosuppressive agents
Insulin
Lipid metabolism
Lipids
Metabolism
Microbiota
Obesity
Oxidation
Phenotypes
Transplantation
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Summary:BackgroundCompared to that of bacteria, the role of gut fungi in obesity development remains unknown.ResultsHere, alterations in gut fungal biodiversity and composition were confirmed in obese pig models and high-fat diet (HFD)-fed mice. Antifungal drugs improved diet-induced obesity, while fungal reconstruction by cohousing or fecal microbiota transplantation maintained the obese phenotype in HFD-fed mice. Fungal profiling identified 5 fungal species associated with obesity. Specifically, Ascomycota_sp. and Microascaceae_sp. were reduced in obese mice and negatively correlated with fat content. Oral supplementation with fungi was sufficient to prevent and treat diet-induced obesity. Clec7a, which is involved in fungal recognition, was highly expressed in HFD-fed mice. The Clec7a agonist accelerated diet-induced obesity, while Clec7a deficieny in mice resulted in resistance to diet-induced obesity and blocked the anti-obese effect of antifungal drugs and fungi.ConclusionsTaken together, these results indicate that gut fungi/Clec7a signaling is involved in diet-induced obesity and may have therapeutic implications as a biomarker for metabolic dysregulation in humans.Video Abstract
ISSN:2049-2618
2049-2618
DOI:10.1186/s40168-023-01698-5