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Protocols for Analyzing the Role of Paneth Cells in Regenerating the Murine Intestine using Conditional Cre-lox Mouse Models
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FABP4 in Paneth cells regulates antimicrobial protein expression to reprogram gut microbiota
Xiaomin Su1, Mengli Jin1,2,3, Chen Xu4
1Department of Immunology, Nankai University School of Medicine; Nankai University, Tianjin, China.
Gut Microbes
|December 15, 2022
Summary
Fatty acid binding protein 4 (FABP4) in gut Paneth cells downregulates defensins, enhancing pathogen resistance. High-fat diets increase FABP4, reducing defensins and altering gut microbiota composition.
Area of Science:
- Gut microbiota and immunology
- Host-pathogen interactions
- Metabolic disease research
Background:
- Antimicrobial proteins, like defensins, are crucial for gut microbiota homeostasis and disease prevention.
- Regulation of defensin expression in gut Paneth cells is not fully understood.
- Gut microbiota dysbiosis is linked to metabolic syndrome and other diseases.
Purpose of the Study:
- To investigate the role of Fatty acid binding protein 4 (FABP4) in regulating defensin expression in gut Paneth cells.
- To elucidate the mechanism by which FABP4 affects defensin levels and its impact on gut immunity.
- To explore the influence of high-fat diet (HFD) on FABP4 expression and defensin regulation in the gut.
Main Methods:
- Utilized FABP4 conditional knockout mice (FABP4fl/flpvillinCreT) to study its function in Paneth cells.
- Assessed resistance to *Salmonella* Typhimurium (S.T) infection and pathogen bactericidal ability.
- Investigated the molecular mechanism involving PPARγ degradation and ubiquitination.
- Analyzed gut microbiota composition using the Firmicutes/Bacteroidetes (F/B) ratio.
Main Results:
- FABP4 in Paneth cells downregulates defensin expression by degrading PPARγ.
- FABP4fl/flpvillinCreT mice exhibit increased resistance to S.T infection and enhanced pathogen killing.
- High-fat diet (HFD) induces FABP4 in Paneth cells, leading to decreased defensin levels.
- FABP4 modulates the gut microbiota composition, indicated by altered F/B ratio, and this effect is conserved in humans.
Conclusions:
- FABP4 acts as a key regulator of defensin expression in gut Paneth cells, impacting host defense and microbiota.
- HFD-induced FABP4 in Paneth cells contributes to defensin downregulation and potential gut dysbiosis.
- Understanding FABP4-mediated defensin regulation offers insights into diseases linked to gut health and diet.
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