'Western Diet'-Induced Adipose Inflammation Requires a Complex Gut Microbiota
| Autor: | Andrew T. Gewirtz, Jun Zou, Benoit Chassaing, Aneseh Adeshirlarijaney, Matam Vijay-Kumar, Timothy L. Denning, Hao Q. Tran, Alexis Bretin, Beng San Yeoh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adipose tissue AST aspartate aminotransferase Gut flora Germ-Free 0302 clinical medicine WSD Western-style diet Antibiotics DC dendritic cells CXCL1 chemokine (C-X-C motif) ligand 1 TNF-α tumor necrosis factor α Original Research Adiposity 2. Zero hunger Metabolic Syndrome Microbiota Gastroenterology High-Fat Diet M2 Macrophage MyD88 myeloid differentiation primary response 88 3. Good health LPS lipopolysaccharide 030211 gastroenterology & hepatology medicine.symptom TLR Toll-like receptor ASF altered Schaedler flora Inflammation Biology Proinflammatory cytokine 03 medical and health sciences FBS fetal bovine serum ALT alanine aminotransferase SVC stromal vascular cells medicine Humans Obesity lcsh:RC799-869 Innate immune system KO knockout Hepatology Altered Schaedler Flora HBSS Hank’s balanced salt solution Dendritic cell biology.organism_classification MyD88 Altered Schaedler flora IL interleukin Gastrointestinal Microbiome GF germ-free PP Peyer’s patches 030104 developmental biology Diet Western Immunology lcsh:Diseases of the digestive system. Gastroenterology |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology Cellular and Molecular Gastroenterology and Hepatology, Vol 9, Iss 2, Pp 313-333 (2020) |
| ISSN: | 2352-345X |
| Popis: | Background & Aims Consumption of a low-fiber, high-fat, Western-style diet (WSD) induces adiposity and adipose inflammation characterized by increases in the M1:M2 macrophage ratio and proinflammatory cytokine expression, both of which contribute to WSD-induced metabolic syndrome. WSD-induced adipose inflammation might result from endoplasmic reticulum stress in lipid-overloaded adipocytes and/or dissemination of gut bacterial products, resulting in activation of innate immune signaling. Hence, we aimed to investigate the role of the gut microbiota, and its detection by innate immune signaling pathways, in WSD-induced adipose inflammation. Methods Mice were fed grain-based chow or a WSD for 8 weeks, assessed metabolically, and intestinal and adipose tissue were analyzed by flow cytometry and quantitative reverse transcription polymerase chain reaction. Microbiota was ablated via antibiotics and use of gnotobiotic mice that completely lacked microbiota (germ-free mice) or had a low-complexity microbiota (altered Schaedler flora). Innate immune signaling was ablated by genetic deletion of Toll-like receptor signaling adaptor myeloid differentiation primary response 88. Results Ablation of microbiota via antibiotic, germ-free, or altered Schaedler flora approaches did not significantly impact WSD-induced adiposity, yet dramatically reduced WSD-induced adipose inflammation as assessed by macrophage populations and cytokine expression. Microbiota ablation also prevented colonic neutrophil and CD103- dendritic cell infiltration. Such reduced indices of inflammation correlated with protection against WSD-induced dysglycemia, hypercholesterolemia, and liver dysfunction. Genetic deletion of myeloid differentiation primary response 88 also prevented WSD-induced adipose inflammation. Conclusions These results indicate that adipose inflammation, and some aspects of metabolic syndrome, are not purely a consequence of diet-induced adiposity per se but, rather, may require disturbance of intestine-microbiota interactions and subsequent activation of innate immunity. Graphical abstract |
| Databáze: | OpenAIRE |
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