High fat diet exacerbates intestinal barrier dysfunction and changes gut microbiota in intestinal-specific ACF7 knockout mice
Autor: | Xiao Qu, Hao Li, Linsheng Huang, Huanlong Qin, Zhenliang Sun, Xuebing Yan, Chenzhang Shi, Cheng Kong |
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Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine endocrine system medicine.medical_specialty RM1-950 Gut flora Diet High-Fat Intestinal barrier function Fat pad Mice Random Allocation 03 medical and health sciences 0302 clinical medicine Internal medicine Conditional gene knockout medicine Animals Obesity Barrier function Mice Knockout Pharmacology Intestinal permeability biology Intestinal microbiology High fat diet Microfilament Proteins digestive oral and skin physiology food and beverages General Medicine Metabolism ACF7 medicine.disease biology.organism_classification Gastrointestinal Microbiome 030104 developmental biology Endocrinology Intestinal Absorption 030220 oncology & carcinogenesis Knockout mouse Therapeutics. Pharmacology Dysbiosis |
Zdroj: | Biomedicine & Pharmacotherapy, Vol 110, Iss, Pp 537-545 (2019) |
ISSN: | 0753-3322 |
DOI: | 10.1016/j.biopha.2018.11.100 |
Popis: | Microtubule-actin cross-linking factor-1 (ACF7, or MACF1) regulates cytoskeletal focal adhesion dynamics and migration in various tissues. High fat diet (HFD) induces gut microbiota dysbiosis and metabolic disorders, and increases intestinal permeability and inflammatory response. Here we investigated the synergistic effects of intestinal ACF7 conditional knockout (ACF7 cKO) and HFD on metabolism phenotypes, gut microbiota and intestinal barrier function in mice. ACF7 cKO and control (ACF7fl/fl) mice (8-week-old) were fed with either chow diet or HFD, for 16 weeks. The increase of body weight and fat pad weight were impaired in HFD-fed ACF7 cKO mice, which can be attributed to decreased food intake and absorption. The metabolic status of HFD-fed ACF7 cKO mice was dramatically changed when compared to the other groups. In addition, HFD-fed ACF7 cKO mice had increased epithelial cell apoptosis, intestinal permeability and inflammatory response when compared with the other groups. The ACF7 cKO-induced changes in alimentation, intestinal barrier function, and gut microbiota were independent of dietary treatment. Taken together, our studies for the first time proved HFD and ACF7 cKO have synergistic damaging effects on intestinal homeostasis. ACF7 is a crucial protective molecule in HFD-induced intestinal diseases. |
Databáze: | OpenAIRE |
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