Intestinal Epithelial Cell-specific Deletion Of Hif1a Affects The Intestinal Barrier Function In High-fat Diet-fed Mice

Background: The damage to intestinal barrier function plays an important role in the development of obesity and associated diseases. Soy isoflavones are effective natural active components for controlling obesity and reducing the level of blood lipid. Here, we explored whether these effects of soy isoflavones were associated with the intestinal barrier function. Methods and Results: The obese rat models were established by high fat diet feeding. Then, those obese rats were supplemented with soy isoflavones at different doses for 4 weeks. Our results showed that obesity induced the expressions of pro-inflammatory cytokines, decreased the anti-inflammatory cytokine (IL-10) expression, elevated intestinal permeability, altered gut microbiota and exacerbated oxidative damages in colon. The administration of soy isoflavones reversed these changes in obese rats, presenting as the improvement of intestinal immune function and permeability, attenuation of oxidative damage, increase in the fraction of beneficial bacteria producing short-chain fatty acids and short-chain fatty acid production, and reduction in harmful bacteria. Furthermore, soy isoflavones blocked the expressions of TLR4 and NF-κB in the colons of the obese rats. Conclusions: Soy isoflavones could improve obesity through the attenuation of intestinal oxidative stress, recovery of immune and mucosal barrier, as well as re-balance of intestinal gut microbiota.

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Intestinal epithelial cell-specific Raptor is essential for high fat diet-induced weight gain in mice

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.10.040 ◽

2018 ◽

Vol 505 (4) ◽

pp. 1174-1179

Author(s):

Emily J. Onufer ◽

Shirli Tay ◽

Lauren K. Barron ◽

Cathleen M. Courtney ◽

Brad W. Warner ◽

...

Keyword(s):

Weight Gain ◽

Epithelial Cell ◽

High Fat Diet ◽

Intestinal Epithelial Cell ◽

Intestinal Epithelial ◽

High Fat

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Fermented blueberry pomace ameliorates intestinal barrier function through the NF-κB-MLCK signaling pathway in high-fat diet mice

Food & Function ◽

10.1039/c9fo02517k ◽

2020 ◽

Vol 11 (4) ◽

pp. 3167-3179 ◽

Cited By ~ 4

Author(s):

Yuxin Cheng ◽

Ting Wu ◽

Shuxin Tang ◽

Fuqiang Liang ◽

Yajing Fang ◽

...

Keyword(s):

Signaling Pathway ◽

Barrier Function ◽

High Fat Diet ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Potential Mechanism ◽

High Fat

The barrier-improving functions of fermented blueberry pomace (FBP) and its potential mechanism were investigated in this study.

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Purified Phlorizin from DocynIa Indica (Wall.) Decne by HSCCC, Compared with Whole Extract, Phlorizin and Non-Phlorizin Fragment Ameliorate Obesity, Insulin Resistance, and Improves Intestinal Barrier Function in High-Fat-Diet-Fed Mice

Molecules ◽

10.3390/molecules23102701 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2701 ◽

Cited By ~ 6

Author(s):

Xiao-yu Zhang ◽

Kang Yi ◽

Jiang Chen ◽

Rui-ping Li ◽

Jie Xie ◽

...

Keyword(s):

Insulin Resistance ◽

Barrier Function ◽

High Fat Diet ◽

High Speed ◽

Intestinal Barrier ◽

Raw Material ◽

Intestinal Barrier Function ◽

Good Effect ◽

High Fat ◽

The Metabolic Syndrome

Natural products generally contain complex and multiple bioactive compounds that are responsible for the effects on health through complicated synergistic and/or suppressive actions. As an important raw material of local ethnic minority tea, ethnomedicines and food supplements in southwestern areas of China, Docynia indica (Wall.) Decne (DID) mainly consists of phlorizin (PHZ), which is the main active component. In this study, the holistic activities and the interactions of components of PHZ, non-phlorizin (NP) in the DID extract (DIDE) were evaluated. A rapid and effective high-speed counter-current chromatography (HSCCC) was performed to knock out PHZ from DIDE and the purity of PHZ was 96.01% determined by HPLC, with a recovery rate of 96.76%. After 13 weeks of treatment course in a high-fat diet (HFD)-induced obese mice model, the results revealed that the DIDE and PHZ significantly decreased weight gain, blood lipid levels, hyperplasia of adipocytes and alleviated inflammation (p < 0.05). Both DIDE and PHZ improves insulin resistance (p < 0.001). Meanwhile, the intestinal barrier function was improved compared to HFD group, through the determination of serum lipopolysaccharides (LPS), glucagon-likepeptide-2 (GLP-2) and hematoxylin-eosin staining of jejunum. Interestingly, after NP treatment, the metabolic syndrome of the HFD-induced obesity appeared to have a similar improvement. All the experiments showed that there is a synergistic weakening phenomenon when PHZ and NP interact with each other in the mixed state. In conclusion, for the PHZ and NP showing a good effect on anti-obesity, anti-inflammation, and intestinal barrier function, DIDE could be a good source of functional food to prevent obesity.

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The combination of Ilexhainanoside D and ilexsaponin A1 reduces liver inflammation and improves intestinal barrier function in mice with high-fat diet-induced non-alcoholic fatty liver disease

Phytomedicine ◽

10.1016/j.phymed.2019.153039 ◽

2019 ◽

Vol 63 ◽

pp. 153039 ◽

Cited By ~ 4

Author(s):

Wenwen Zhao ◽

Meng Xiao ◽

Jie Yang ◽

Li Zhang ◽

Yinying Ba ◽

...

Keyword(s):

Liver Disease ◽

Barrier Function ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Liver Inflammation ◽

High Fat ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

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Curcumin prevents high-fat diet-induced hepatic steatosis in ApoE−/− mice by improving intestinal barrier function and reducing endotoxin and liver TLR4/NF-κB inflammation

Nutrition & Metabolism ◽

10.1186/s12986-019-0410-3 ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 6

Author(s):

Dan Feng ◽

Jun Zou ◽

Dongfang Su ◽

Haiyan Mai ◽

Shanshan Zhang ◽

...

Keyword(s):

Liver Disease ◽

Hepatic Steatosis ◽

Barrier Function ◽

High Fat Diet ◽

Intestinal Barrier ◽

Liver Weight ◽

Health Concern ◽

Intestinal Barrier Function ◽

High Fat ◽

Tnf Α

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and has become a public health concern worldwide. The hallmark of NAFLD is hepatic steatosis. Therefore, there is an urgent need to develop new therapeutic strategies that are efficacious and have minimal side effects in hepatic steatosis and NAFLD treatment. The present study aimed to investigate the effect of dietary supplement of curcumin on high-fat diet (HFD)-induced hepatic steatosis and the underlying mechanism. Methods ApoE−/− mice were fed a normal diet, high-fat diet (HFD) or HFD supplemented with curcumin (0.1% w/w) for 16 weeks. Body and liver weight, blood biochemical. parameters, and liver lipids were measured. Intestinal permeability, hepatic steatosis and mRNA and protein expressions of TLR4-related inflammatory signaling molecule were analyzed. Results The administration of curcumin significantly prevented HFD-induced body weight gain and reduced liver weight. Curcumin attenuated hepatic steatosis along with improved serum lipid profile. Moreover, curcumin up-regulated the expression of intestinal tight junction protein zonula occluden-1 and occludin, which further improved gut barrier dysfunction and reduced circulating lipopolysaccharide levels. Curcumin also markedly down-regulated the protein expression of hepatic TLR4 and myeloid differentiation factor 88 (MyD88), inhibited p65 nuclear translocation and DNA binding activity of nuclear factor-κB (NF-κB) in the liver. In addition, the mRNA expression of hepatic tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) as well as the plasma levels of TNF-α and IL-1β were also lowered by curcumin treatment. Conclusion These results indicated that curcumin protects against HFD-induced hepatic steatosis by improving intestinal barrier function and reducing endotoxin and liver TLR4/NF-κB inflammation. The ability of curcumin to inhibit hepatic steatosis portrayed its potential as effective dietry intervention for NAFLD prevention.

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Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00256.2015 ◽

2015 ◽

Vol 309 (12) ◽

pp. G988-G997 ◽

Cited By ~ 48

Author(s):

Prashant Nighot ◽

Rana Al-Sadi ◽

Manmeet Rawat ◽

Shuhong Guo ◽

D. Martin Watterson ◽

...

Keyword(s):

Epithelial Cell ◽

Protein Expression ◽

Barrier Function ◽

Intestinal Inflammation ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Intestinal Epithelial ◽

Dss Colitis

Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9−/−mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9−/−mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9−/−mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK−/−mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9−/−mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK.

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STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis

Biomedicines ◽

10.3390/biomedicines9020187 ◽

2021 ◽

Vol 9 (2) ◽

pp. 187

Author(s):

Lokman Pang ◽

Jennifer Huynh ◽

Mariah G. Alorro ◽

Xia Li ◽

Matthias Ernst ◽

...

Keyword(s):

Barrier Function ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Intestinal Epithelial ◽

Barrier Dysfunction ◽

Epithelial Integrity ◽

Barrier Integrity ◽

Gp130 Receptor ◽

Stat3 Signalling

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.

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