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Paula Mosińska, Adrian Szczepaniak, Jakub Fichna
Functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome (IBS) and chronic constipation (CC), are commonly diagnosed conditions in clinical practice which create a substantial global burden. Since the farnesoid X receptor (FXR) and bile acids (BAs) are responsible for maintaining homeostasis in the GI tract, any disturbances in the expression of FXR or the composition of BAs may contribute to the development of the GI symptoms. Alterations in the mechanism of action of FXR directly affect the BAs pool and account for increased intestinal permeability and changes in abundance and diversity of gut microbiota leading to intestinal dysmotility...
May 30, 2018: Digestive and Liver Disease
Yujie Liu, An Song, Xi Yang, Yunfeng Zhen, Weiwei Chen, Linquan Yang, Chao Wang, Huijuan Ma
The development of type‑2 diabetes and its complications is associated with lipid metabolism disorder. Farnesoid X receptor (FXR) has an important role in regulating lipid and glucose metabolism. However, the underlying mechanism of this remains unclear. The present study investigated the role of fexaramine (Fex), an FXR agonist, on lipid metabolism. For this purpose, 6‑week‑old db/db mice were treated with Fex for 8 weeks via oral gavage and db/db mice treated with corn oil were used as controls. Body weight and food intake were monitored daily and bi‑weekly, respectively...
June 5, 2018: International Journal of Molecular Medicine
Prasant Kumar Jena, Lili Sheng, Nidhi Nagar, Chao Wu, Daniela Barile, David A Mills, Yui-Jui Yvonne Wan
Probiotic Bifidobacterium longum subspecies infantis ( Bifidobacterium infantis ) consumes human milk oligosaccharides (MO) and protects intestinal permeability thereby having anti-inflammatory effects (Underwood et al., 2015; Bode, 2006; Asakuma et al., 2011) [1-3]. Via the gut-liver axis, gut barrier disruption and dysbiosis lead to hepatic inflammation (Sheng et al., 2017; Jena et al., 2017) [4,5,6]. Our published data revealed that butyrate, as well as synbiotics of B. infantis in combination with MO, had protective effects against cancer-prone non-alcoholic steatohepatitis (NASH) mouse models, i...
August 2018: Data in Brief
Lile Dong, Xu Han, Xufeng Tao, Lina Xu, Youwei Xu, Linlin Fang, Lianhong Yin, Yan Qi, Hua Li, Jinyong Peng
We previously reported the effects of the total flavonoids (TFs) from Rosa laevigata Michx fruit against carbon tetrachloride-induced liver damage, non-alcoholic fatty liver disease, and liver ischemia-reperfusion injury. However, there have been no papers reporting the role of R. laevigata TFs against lipopolysaccharide (LPS)-induced liver injury. In this paper, liver injury in mice was induced by LPS, and R. Laevigata extract was intragastrically administered to the mice for 7 days. Biochemical parameters in serum and liver tissue were examined, and pathological changes were observed by transmission electron microscopy, hematoxylin and eosin (H&E) and Oil Red O staining...
June 8, 2018: Foods (Basel, Switzerland)
Shuqi Pu, Xiaojie Wu, Xiaoying Yang, Yunzhan Zhang, Yunkai Dai, Yueling Zhang, Xiaoting Wu, Yan Liu, Xiaona Cui, Haiyong Jin, Jianhong Cao, Ruliu Li, Jiazhong Cai, Qizhi Cao, Ling Hu, Yong Gao
Xenobiotic nuclear receptors (XNRs) are nuclear receptors that characterized by coordinately regulating the expression of genes encoding drug-metabolizing enzymes and transporters to essentially eliminate and detoxify xenobiotics and endobiotics from the body, including the peroxisome proliferator-activated receptor (PPAR), the farnesoid X receptor (FXR), the liver X receptor (LXR), the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). Heretofore, increasing evidences have suggested that these five XNRs are not only involved in the regulation of xeno-/endo-biotics detoxication but also the development of human diseases, such as cancer, obesity and diabetes...
June 10, 2018: Current Drug Metabolism
Faten A Al-Aqil, Maria J Monte, Ana Peleteiro-Vigil, Oscar Briz, Ruben Rosales, Raquel Gonzalez, Carlos J Aranda, Borja Ocon, Iker Uriarte, Fermin Sanchez de Medina, Olga Martinez-Augustin, Matias A Avila, Jose J G Marin, Marta R Romero
At high doses, glucocorticoids (GC) have been associated with enhanced serum bile acids and liver injury. We have evaluated the effect of GC, in the absence of hepatotoxicity, on FXR/Fgf15/Fgf21-mediated ileum-liver crosstalk. Rats and mice (wild type and Fxr-/- , Fgf15-/- and int-Gr-/- strains; the latter with GC receptor (Gr) knockout selective for intestinal epithelial cells), were treated (i.p.) with dexamethasone, prednisolone or budesonide. In both species, high doses of GC caused hepatotoxicity. At a non-hepatotoxic dose, GC induced ileal Fgf15 down-regulation and liver Fgf21 up-regulation, without affecting Fxr expression...
June 5, 2018: Biochimica et Biophysica Acta
Lili Sheng, Prasant Kumar Jena, Hui-Xin Liu, Ying Hu, Nidhi Nagar, Denise N Bronner, Matthew L Settles, Andreas J Bäumler, Yu-Jui Yvonne Wan
Dysregulated bile acid (BA) synthesis is accompanied by dysbiosis, leading to compromised metabolism. This study analyzes the effect of epigallocatechin-3-gallate (EGCG) on diet-induced obesity through regulation of BA signaling and gut microbiota. The data revealed that EGCG effectively reduced diet-increased obesity, visceral fat, and insulin resistance. Gene profiling data showed that EGCG had a significant impact on regulating genes implicated in fatty acid uptake, adipogenesis, and metabolism in the adipose tissue...
June 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Yifeng Wang, David Matye, Nga Nguyen, Yuxia Zhang, Tiangang Li
BACKGROUND: cysteine dioxygenase 1 (CDO1) converts cysteine to cysteine sulfinic acid, which can be further converted by cysteine sulfinic acid decarboxylase (CSAD) to hypotaurine for taurine production. This cysteine catabolic pathway plays a major role in regulating hepatic cysteine homeostasis. Furthermore, taurine is used for bile acid conjugation, which enhances bile acid solubility and physiological function in the gut. Recent studies show that this cysteine catabolic pathway is repressed by bile acid signaling, but the molecular mechanisms have not been fully elucidated...
June 5, 2018: Gene Expression
Dana Friedrich, Hanns-Ulrich Marschall, Frank Lammert
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is common both in obese and overweight patients. Fibroblast growth factor 19 (FGF19), an intestinal hormone, could play a role in the complex pathogenesis of NAFLD. The aim of our study was to investigate responses of FGF19 and bile acid (BA) synthesis after a body weight-adjusted oral fat tolerance test (OFTT) in overweight and obese NAFLD patients. METHODS: For this study, we recruited 26 NAFLD patients; 14 overweight (median BMI 28...
June 4, 2018: BMC Gastroenterology
Lisa Rizzetto, Francesca Fava, Kieran M Tuohy, Carlo Selmi
Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically...
May 31, 2018: Journal of Autoimmunity
Caixia Yan, Yirui Zhang, Xiaoxu Zhang, Jiye Aa, Guangji Wang, Yuan Xie
BACKGROUND: Curcumin is a natural polyphenol with beneficial effects on NAFLD patients and NAFLD is accompanied by metabolism decompensation. METHODS: This study was focused on the effect of curcumin on the relationship between endogenous bile acids metabolism pathway and exogenous xenobiotics metabolism pathway in C57BL/6 mice of non-alcoholic fatty liver disease induced by high-fat and high-fructose diet (HFHFr) and in cultured mice hepatocytes. RESULTS: Our results showed curcumin treatment apparently attenuated the hepatic steatosis and reversed the abnormalities of serum biochemical parameters in HFHFr-fed mice...
May 31, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Haining Zhou, Zhen Ni, Ting Li, Linna Su, Lianfeng Zhang, Na Liu, Yongquan Shi
Gastric intestinal metaplasia (IM) induced by bile acid is a precancerous lesion of gastric adenocarcinoma and is associated with the expression of caudal-related homeobox 2 (CDX2). In the present study, the role of farnesoid X receptor (FXR) on the regulation of CDX2 in gastric cells was investigated and the underlying molecular mechanisms were examined. Human gastric cell lines were treated with chenodeoxycholic acid (CDCA) or FXR agonist GW4064. Cells were treated with CDCA in the presence or absence of the FXR antagonist or FXR siRNA transfection...
May 2018: Oncology Letters
Chen Chen, Paulus Jochems, Lucia Salz, Kerstin Schneeberger, Louis C Penning, Stan F J van de Graaf, Ulrich Beuers, Hans Clevers, Niels Geijsen, Rosalinde Masereeuw, Bart Spee
Investigation of diseases of the bile duct system and identification of potential therapeutic targets are hampered by the lack of tractable in vitro systems to model cholangiocyte biology. Here, we show a step-wise method for the differentiation of murine Lgr5+ liver stem cells (organoids) into cholangiocyte-like cells (CLCs) using a combination of growth factors and extracellular matrix components. Organoid-derived CLCs display key properties of primary cholangiocytes, such as expressing cholangiocyte markers, forming primary cilia, transporting small molecules and responding to farnesoid X receptor (FXR) agonist...
May 31, 2018: Biofabrication
Jian Xu, Yong Wang, Jiajun Yin, Min Yin, Mofei Wang, Jingang Liu
Farnesoid X receptor (FXR) and related pathways are involved in the therapeutic effect of sleeve gastrectomy for overweight or obese patients with diabetes mellitus. This study aimed to investigate the mechanism of FXR expression regulation during the surgical treatment of obese diabetes mellitus by sleeve gastrectomy. Diabetic rats were established by combined streptozotocin and high-fat diet induction. Data collection included body weight, chemical indexes of glucose and lipid metabolism, liver function, and the expression levels of musculoaponeurotic fibrosarcoma oncogene family B (MAFB), FXR, and related genes induced by sleeve gastrectomy...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Toshihiro Goto, Michiko Itoh, Takayoshi Suganami, Sayaka Kanai, Ibuki Shirakawa, Takeru Sakai, Masahiro Asakawa, Toshihiro Yoneyama, Toshihiro Kai, Yoshihiro Ogawa
Accumulating evidence has suggested that farnesoid X receptor (FXR) agonists, such as obeticholic acid (OCA) are therapeutically useful for non-alcoholic steatohepatitis (NASH). However, it is still unclear how FXR agonists protect against NASH and which cell type is the main target of FXR agonists. In this study, we examined the effects of OCA on the development of NASH using melanocortin 4 receptor-deficient (MC4R-KO) mice that progressively developed hepatic steatosis and NASH on Western diet (WD). Treatment with OCA effectively prevented chronic inflammation and liver fibrosis in WD-fed MC4R-KO mice with only marginal effect on body weight and hepatic steatosis...
May 25, 2018: Scientific Reports
Prasant Kumar Jena, Lili Sheng, Nidhi Nagar, Chao Wu, Daniela Barile, David A Mills, Yui-Jui Yvonne Wan
Milk oligosaccharides (MO) selectively increase the growth of Bifidobacterium infantis (B. infantis). This study examines the effects of bovine MO and B. infantis in preventing nonalcoholic steatohepatitis (NASH) in Western diet (WD)-fed bile acid (BA) receptor FXR (farnesoid x receptor) knockout (KO) mice. WD-fed FXR KO mice have cancer-prone NASH and reduced B. infantis. MO and/or B. infantis supplementation improved their insulin sensitivity and reduced hepatic inflammation. Additionally, B. infantis, but not MO, decreased hepatic triglyceride and cholesterol...
April 25, 2018: Journal of Nutritional Biochemistry
Yunyun Pan, Fenghua Zhou, Zhenhua Song, Huiping Huang, Yong Chen, Yonggang Shen, Yuhua Jia, Jisheng Chen
Atherosclerosis, the leading cause of cardiovascular diseases in the world, is a chronic inflammatory disorder characterized by the dysfunction of arteries. Oleanolic acid (OA) is a bioactive nature product which exists in various plants and herbs. Previous studies have demonstrated that OA was involved in numerous of biological processes, including atherosclerosis. However, the exact mechanisms of the anti-atherosclerosis effects of OA remain unknown. Here, in our study, we analyzed the effects and possible underlying mechanisms of OA in atherosclerosis depending a cell model and an animal model of atherosclerosis...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Shuang Rong, Siqi Zhao, Xu Kai, Li Zhang, Yanting Zhao, Xiao Xiao, Wei Bao, Liegang Liu
The beneficial effects of red wine against cardiovascular disease are associated with the abundant antioxidant polyphenols such as procyanidins. Recently, procyanidins extracted from the litchi pericarp (LPPC), a new source of procyanidins showed strong antioxidant activities in vitro, have been isolated and identified in our laboratory. The aim of present study was to investigate the anti-atherosclerotic effects of LPPC on atherosclerosis and hyperlipidemia in apolipoprotein E knockout (ApoE KO) mice fed a high fat diet (HFD, 21% fat, 0...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zhi-Qiang Liu, Joon No Lee, Myeongjoo Son, Jae-Young Lim, Raghbendra Kumar Dutta, Yunash Maharjan, SeongAe Kwak, Goo Taeg Oh, Kyunghee Byun, Seong-Kyu Choe, Raekil Park
The primary cilia are evolutionarily conserved microtubule-based cellular organelles that perceive metabolic status and thus link the sensory system to cellular signaling pathways. Therefore, ciliogenesis is thought to be tightly linked to autophagy, which is also regulated by nutrient-sensing transcription factors, such as PPARA (peroxisome proliferator activated receptor alpha) and NR1H4/FXR (nuclear receptor subfamily 1, group H, member 4). However, the relationship between these factors and ciliogenesis has not been clearly demonstrated...
May 17, 2018: Autophagy
Zhi-Ming Ding, Yue Xiao, Xikun Wu, Haixia Zou, Shurong Yang, Yiyun Shen, Juehua Xu, Heather C Workman, Amy L Usborne, Haiqing Hua
Understanding of the temporal changes of hepatic lesions in the progression and regression of non-alcoholic steatohepatitis (NASH) is vital to elucidation of the pathogenesis of NASH, and critical to the development of a strategy for NASH pharmacotherapy. There are challenges in studying hepatic lesion progression and regression in NASH patients due to the slow development of NASH in humans, one being the requirement for multiple biopsies during the longitudinal follow-up. Here we studied lesion progression and regression in the diet-induced animal model of NASH by application or removal of the pathogenic diet for multiple time periods...
2018: Frontiers in Pharmacology
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