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PFOA/PFOS Facilitated intestinal Fatty Acid Absorption by Activating the PPARαPathway:Insights from organoids Model

Environment & Health 2024年第2期2卷 85-94页

作者： Wen Zhang Yushan Tian Biao Chen Shengmin Xu Lijun Wu Information Materials and Intelligent Sensing Laboratory of Anhui Province Institutes of Physical Science and Information TechnologyAnhui UniversityHefeiAnhui 230601China China National Tobacco Quality Supervision and Test Center ZhengzhouHenan 450001China

Perfluorooctanoic acid(PFOA)and perfluorooctanesulfonate(PFOS)continue to be extensively present in the natural environment and seriously threaten human *** intestinal tract is the primary organ of PFOA/PFOS exposure due to the consumption of contaminated food and drinking ***,it remains unclear how PFOA/PFOS affects intestinal function and overall *** aim of this study was to investigate the influence of PFOA/PFOS on the absorption of fatty acids in the intestine and the underlying mechanisms using three-dimensional(3D)intestinal *** results showed that PFOS,but not PFOA,could significantly enhance the fatty acid uptake capacity without obvious damage to the ***,PFOS markedly reduced the protein levels of ChgA in enteroendocrine cells,but with no observed impact on aldolase B+***,exposure to PFOS induced the activation of the peroxisome proliferator-activated receptor(PPAR)αpathway in intestinal organoids,with enhanced expression of PPARαtarget genes associated with fatty acid metabolism,such as Fabp1 and Cd36(fatty acid transporter genes),Acox1 and Pdk4(fatty acid oxidation genes),and Plin2 and Plin3(lipid droplet synthesis genes).These data suggest that PFOS have the potential to affect the absorption function of the intestinal epithelium through the PPARαpathway,and its effect is much stronger than that of *** findings also highlight that organoids can be used as a valuable model for conducting toxicological research on environmental chemicals.

关键词： PFOA PFOS intestinal organoids fatty acid absorption enteroendocrine cells PPARα

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Current knowledge on the multiform reconstitution of intestinal stem cell niche

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World Journal of Stem Cells 2021年第10期13卷 1564-1579页

作者： Zi-Yan Xu Jin-Jian Huang Ye Liu Yun Zhao Xiu-Wen Wu Jian-An Ren Research Institute of General Surgery Jinling HospitalMedical School of Nanjing UniversityNanjing 210002Jiangsu ProvinceChina Medical School Southeast UniversityNanjing 210009Jiangsu ProvinceChina Department of General Surgery BenQ Medical CenterNanjing 210019Jiangsu ProvinceChina

The development of“mini-guts”organoid originates from the identification of Lgr5+intestinal stem cells(ISCs)and circumambient signalings within their specific niche at the crypt *** in vitro self-renewing“mini-guts”,also named enteroids or colonoids,undergo perpetual proliferation and regulated differentiation,which results in a high-performance,self-assembling and physiological organoid platform in diverse areas of intestinal research and *** triumphant reconstitution of ISC niche in vitro also relies on Matrigel,a heterogeneous sarcoma *** the promising prospect of organoids research,their expanding applications are hampered by the canonical culture pattern,which reveals limitations such as inaccessible lumen,confine scale,batch to batch variation and low *** tumor-origin of Matrigel also raises biosafety concerns in clinical ***,the convergence of breakthroughs in cellular biology and bioengineering contribute to multiform reconstitution of the ISC ***,we review the recent advances in the microfabrication of intestinal organoids on hydrogel systems.

关键词： intestinal organoids Reconstitution Stem cell niche Bioengineering Hydrogel

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Effects of undigested protein-rich ingredients on polarised small intestinal organoid monolayers

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Journal of Animal Science and Biotechnology 2020年第4期11卷 1026-1032页

作者： Soumya K.Kar Bart van der Hee Linda M.P.Loonen Nico Taverne Johanna J.Taverne-Thiele Dirkjan Schokker Mari A.Smits Alfons J.M.Jansman Jerry M.Wells Host Microbe Interactomics Group Wageningen University&ResearchDe Elst 16708 WD WageningenThe Netherlands Laboratory of Microbiology Wageningen University&ResearchStippeneng 46708 WE WageningenThe Netherlands Wageningen Livestock Research Wageningen University&ResearchDe Elst 16708 WD WageningenThe Netherlands

Here, we describe the use of monolayers of intestinal epithelial cells derived from intestinal organoids and transcriptomics to investigate the direct effects of dietary protein sources on epithelial function. Mechanically dissociated 3 D organoids of mouse duodenum were used to generate a polarized epithelium containing all cell types found in the tissue of origin. The organoid-derived cell monolayers were exposed to 4%(w/v) of ‘undigested(non-hydrolysed)-soluble' fraction of protein sources used as feed ingredients [soybean meal(SBM) and casein], or alternative protein sources(spray dried plasma protein, and yellow meal worm), or controls for 6 h prior to RNA isolation and transcriptomics. All protein sources altered expression of unique biological processes in the epithelial cells. Exposure of intestinal organoids to SBM downregulated expression of retinol and retinoid metabolic processes as well as cholesterol and lipid biosynthetic pathways, consistent with the reported hypotriglyceridaemic effect of soy protein in vivo. These findings support the use of intestinal organoids as models to evaluate complex interactions between dietary ingredients and the intestinal epithelium and highlights some unique host effects of alternative protein sources in animal feed and potentially human food.

关键词： Alternative protein sources Casein intestinal organoids organoids Soybean meal Spray dried plasma protein Transcriptomics Yellow meal worm

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