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https://www.readbyqxmd.com/read/28202906/bar502-a-dual-fxr-and-gpbar1-agonist-promotes-browning-of-white-adipose-tissue-and-reverses-liver-steatosis-and-fibrosis
#1
Adriana Carino, Sabrina Cipriani, Silvia Marchianò, Michele Biagioli, Chiara Santorelli, Annibale Donini, Angela Zampella, Maria Chiara Monti, Stefano Fiorucci
Non-alcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease. Here, we have investigated whether BAR502, a non-bile acid, steroidal dual ligand for FXR and GPBAR1, reverses steato-hepatitis in mice fed a high fat diet (HFD) and fructose. After 9 week, mice on HFD gained ≈30% of b.w (P < 0.01 versus naïve) and were insulin resistant. These overweighting and insulin resistant mice were randomized to receive HFD or HFD in combination with BAR502. After 18 weeks, HFD mice developed NASH like features with severe steato-hepatitis and fibrosis, increased hepatic content of triacylglycerol and cholesterol and expression of SREPB1c, FAS, ApoC2, PPARα and γ, α-SMA, α1 collagen and MCP1 mRNAs...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199789/plasma-cholesterol-lowering-activity-of-tartary-buckwheat-protein
#2
Chengnan Zhang, Rui Zhang, Yuk Man Li, Ning Liang, Yimin Zhao, Hanyue Zhu, Zouyan He, Jianhui Liu, Wangjun Hao, Rui Jiao, Ka Ying Ma, Zhen-Yu Chen
Previous research has shown Tartary buckwheat flour is capable of reducing plasma cholesterol. The present study was to examine the effect of rutin and Tartary buckwheat protein on plasma total cholesterol (TC) in hypercholesterolemia hamsters. In the first animal experiment, 40 male hamsters were divided into four groups fed either the control diet or one of the three experimental diets containing 8.2 mmol rutin, 8.2 mmol quercetin, and 2.5 g kg-1 cholestyramine, respectively. Result showed that only cholestyramine but not rutin and its aglycone quercetin decreased plasma TC, suggesting rutin was not the active ingredient responsible for plasma TC-lowering activity of Tartary buckwheat flour...
February 15, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28169529/deacetylated-konjac-glucomannan-is-less-effective-in-reducing-dietary-induced-hyperlipidemia-and-hepatic-steatosis-in-c57bl-6-mice
#3
Meiying Li, Guanping Feng, Hong Wang, Ruili Yang, Zhenlin Xu, Yuanming Sun
Konjac gel foods that mainly consist of deacetylated konjac glucomannan (Da-KGM) are considered to have the same health benefits as native konjac glucomannan (KGM); however, no definitive data support this notion. The objective of this study was to compare the effects of Da-KGM and KGM on the hyperlipidemia and liver steatosis induced by high-fat diet feeding and to investigate the underlying molecular mechanisms. C57BL/6 mice were fed (1) normal chow diet; (2) high-fat diet; (3) HFD with KGM; (4) HFD with Da-KGM for 10 weeks...
February 7, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28161535/4-o-sulfation-in-sea-cucumber-fucodians-contribute-to-reversing-dyslipidiaemia-caused-by-hfd
#4
Shan Li, Junhui Li, Zijian Zhi, Yaqin Hu, Jian Ge, Xingqian Ye, Ding Tian, Linhardt Robert, Shiguo Chen
Fucodians extracted from sea cucumbers (SC-FUCs) possess linear chains with uniform repeating units. Sulfation patterns endow SC-FUCs unique structures and bioactivity. The present study investigated the anti-hyperlipidemic activity of two fucodians isolated from sea cucumbers Pearsonothuria graeffei (fuc-Pg) and Isostichopus badionotus (fuc-Ib). The results indicate fuc-Pg dominated with a 4-O-sulfation pattern shows strong activity in reducing body weight, regulating lipid disorder (TC, TG, HLD-C, and LDL-C level), improving liver function (liver weight, GOP, GPT, and TBA concentrations) and increasing adiponectin level (adiponectin concentration) caused by HFD...
February 1, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28130274/commensal-bacteria-at-the-crossroad-between-cholesterol-homeostasis-and-chronic-inflammation-in-atherosclerosis
#5
Kazuyuki Kasahara, Takeshi Tanoue, Tomoya Yamashita, Keiko Yodoi, Takuya Matsumoto, Takuo Emoto, Taiji Mizoguchi, Tomohiro Hayashi, Naoki Kitano, Naoto Sasaki, Koji Atarashi, Kenya Honda, Ken-Ichi Hirata
The gut microbiota were shown to play critical roles in the development of atherosclerosis, but the detailed mechanism is limited. The purpose of this study is to clarify the influence of gut microbiota on atherogenesis via lipid metabolism and systemic inflammation. Germ-free (GF) or conventionally raised (Conv) Apolipoprotein E deficient (ApoE(-/-)) mice were fed chow diet and sacrificed at twenty weeks of age. We found lack of gut microbiota in ApoE(-/-) mice caused a significant increase in the plasma and hepatic cholesterol levels compared to ConvR ApoE(-/-) mice...
January 27, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28127194/three-dimensional-perfused-human-in-vitro-model-of-non-alcoholic-fatty-liver-disease
#6
Tomasz Kostrzewski, Terri Cornforth, Sophie A Snow, Larissa Ouro-Gnao, Cliff Rowe, Emma M Large, David J Hughes
AIM: To develop a human in vitro model of non-alcoholic fatty liver disease (NAFLD), utilising primary hepatocytes cultured in a three-dimensional (3D) perfused platform. METHODS: Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids (FFA) from culture medium was monitored...
January 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28095641/melatonin-ameliorates-alcohol-induced-bile-acid-synthesis-by-enhancing-mir-497-expression
#7
Yong Deuk Kim, Seung-Lark Hwang, Eun-Joo Lee, Hyeong-Mi Kim, Myung-Jin Chung, Ahmed K Elfadl, Sung-Eun Lee, Balachandar Nedumaran, Robert A Harris, Kyu-Shik Jeong
Alcoholic liver disease is a major cause of chronic liver disease worldwide and cannabinoid receptor type 1 (CB1R) is involved in a diverse metabolic diseases. B-cell translocation gene 2 (BTG2) and yin yang 1 (YY1) are a potent regulator of biological conditions. Melatonin plays a crucial role in regulating diverse physiological functions and metabolic homeostasis. MicroRNAs are key regulators of various biological processes. Herein, we demonstrate that melatonin improves bile acid synthesis in the liver of alcohol-fed mice by controlling miR-497 expression...
January 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28091360/collagen-peptide-ingestion-alters-lipid-metabolism-related-gene-expression-and-the-unfolded-protein-response-in-mouse-liver
#8
Chisa Tometsuka, Yoh-Ichi Koyama, Tomoko Ishijima, Tsudoi Toyoda, Miki Teranishi, Kazushige Takehana, Keiko Abe, Yuji Nakai
Ingestion of collagen peptide (CP) elicits beneficial effects on the body, including improvement in blood lipid profiles, but the underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of CP ingestion on the liver, which controls lipid metabolism in the body. Male BALB/cCrSlc mice were bred with the AIN-93M diet containing 14 % casein or the AIN-93M-based low-protein diet containing 10 % casein or a diet containing 6 % casein+4 % CP for 10 weeks (n 12/group). Total, free and esterified cholesterol levels in the blood decreased in the CP group...
January 16, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28067465/cholestyramine-alters%C3%A2-bile-acid%C3%A2-amounts-and-the-expression-of-cholesterol-related-genes-in-rabbit-intestinal-and-hepatic-tissues
#9
Dong Ni Qiu, Quan Shang, Da Yu Sun, Wei Qun Ding, Zhong Guang Luo, Jian Chen, Wei Ru Jiang, Jian Ping Huang, Xiao Yun Jiang
OBJECTIVE: Cholestyramine, as a bile acid sequestering exchange resin, has been wildly used to treat hypercholesterolemia. The aim of this study was to explore how cholestyramine regulated serum cholesterol amounts and bile acid levels in animal models. METHODS: The New Zealand White rabbits were randomly assigned to the control (given distilled water) and cholestyramine (CHO)-treated (given cholestyramine 1 g/kg/day for 2 weeks) groups. To assess bile acid pool size, bile fistulas were generated in five rabbits in each group...
January 9, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28056490/knockout-of-the-primary-sclerosing-cholangitis-risk-gene-fut2-causes-liver-disease-in-mice
#10
Luca Maroni, Simon D Hohenester, Stan F J van de Graaf, Dagmar Tolenaars, Krijn van Lienden, Joanne Verheij, Marco Marzioni, Tom H Karlsen, Ronald P J Oude Elferink, Ulrich Beuers
: The etiopathogenesis of primary sclerosing cholangitis (PSC) is unknown. Genetic variants of fucosyltransferase 2 (FUT2) have been identified in genome-wide association studies as risk factor for PSC. We investigated the role of Fut2 in murine liver pathophysiology by studying Fut2(-/-) mice. Fut2(-/-) mice were viable and fertile, had lower body weight than wild type (wt) littermates and grey fur, as described earlier. Half of the Fut2(-/-) mice showed serum bile salt levels 40 times higher than wt (Fut2(-/-)(high) ), whereas the remainder were normocholanemic (Fut2(-/-)(low) )...
January 5, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28051334/glutamine-attenuates-obstructive-cholestasis-in-rats-via-farnesoid-x-receptor-mediated-regulation-of-bsep-and-mrp2
#11
Bingli Liu, Yiming Li, Hong Ji, Hongwei Lu, Hua Li, Yakun Shi
To investigate the protective effect of glutamine (Gln) against obstructive cholestasis in association with farnesoid X receptor (FXR) activation, an obstructive cholestasis model was established in male Sprague-Dawley rats by bile duct ligation (BDL). Serum biomarkers and hematoxylin plus eosin staining were used to identify the degree of hepatic injury in the rats with obstructive cholestasis after Gln treatment. Immunohistochemistry, real-time PCR, Western blot, cultured primary rat hepatocytes with FXR knockdown, and dual-luciferase reporter assay were performed to elucidate the mechanisms underlying Gln hepatoprotection...
October 5, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28041926/chronic-over-expression-of-fibroblast-growth-factor-21-increases-bile-acid-biosynthesis-by-opposing-fgf15-19-action
#12
Jun Zhang, Jamila Gupte, Yan Gong, Jennifer Weiszmann, Yuan Zhang, Ki Jeong Lee, William G Richards, Yang Li
Pharmacological doses of fibroblast growth factor (FGF) 21 effectively normalize glucose, lipid and energy homeostasis in multiple animal models with many benefits translating to obese humans with type 2 diabetes. However, a role for FGF21 in the regulation of bile acid metabolism has not been reported. Herein, we demonstrate AAV-mediated FGF21 overexpression in mice increases liver expression of the key bile acid producing enzyme, Cyp7a1, resulting in an increased bile acid pool. Furthermore, in cholecystectomized mice, FGF21-mediated bile acid pool increase led to increased transit of bile acids into colon...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28039934/prostaglandin-e2-promotes-hepatic-bile-acid-synthesis-by-an-e-prostanoid-receptor-3-mediated-hepatocyte-nuclear-receptor-4%C3%AE-cholesterol-7%C3%AE-hydroxylase-pathway-in-mice
#13
Shuai Yan, Juan Tang, Yuyao Zhang, Yuanyang Wang, Shengkai Zuo, Yujun Shen, Qianqian Zhang, Di Chen, Yu Yu, Kai Wang, Sheng-Zhong Duan, Ying Yu
: Prostaglandin E2 (PGE2 ) is an important lipid mediator of inflammation. However, whether and how PGE2 regulates hepatic cholesterol metabolism remains unknown. We found that expression of the PGE2 receptor, E prostanoid receptor 3 (EP3) expression is remarkably increased in hepatocytes in response to hyperlipidemic stress. Hepatocyte-specific deletion of EP3 receptor (EP3(hep-/-) ) results in hypercholesterolemia and augments diet-induced atherosclerosis in low-density lipoprotein receptor knockout (Ldlr(-/-) ) mice...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28039331/hepatic-deletion-of-x-box-binding-protein-1-impairs-bile-acid-metabolism-in-mice
#14
Xiaoying Liu, Anne S Henkel, Brian E LeCuyer, Susan C Hubchak, Matthew J Schipma, Eric Zhang, Richard M Green
The unfolded protein response (UPR) is an adaptive response to endoplasmic reticulum stress and the inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1) pathway of the UPR is important in lipid metabolism. However, its role in bile acid metabolism remains unknown. We demonstrate that liver-specific Xbp1 knockout (LS-Xbp1(-/-)) mice had a 45% reduction in total bile acid pool. LS-Xbp1(-/-) mice had lower serum 7α-hydroxy-4-cholesten-3-one (C4) levels compared to Xbp1(fl/fl) mice, indicating reduced CYP7A1 synthetic activity...
December 30, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/28029505/parenteral-nutrition-dysregulates-bile-salt-homeostasis-in-a-rat-model-of-parenteral-nutrition-associated-liver-disease
#15
Kiran V K Koelfat, Frank G Schaap, Caroline M J M Hodin, Ruben G J Visschers, Björn I Svavarsson, Martin Lenicek, Ronit Shiri-Sverdlov, Kaatje Lenaerts, Steven W M Olde Damink
BACKGROUND & AIMS: Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis...
September 24, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28013406/simulated-microgravity-affects-some-biological-characteristics-of-lactobacillus-acidophilus
#16
Dongyan Shao, Linbo Yao, Muhammad Shahid Riaz, Jing Zhu, Junling Shi, Mingliang Jin, Qingsheng Huang, Hui Yang
The effects of weightlessness on enteric microorganisms have been extensively studied, but have mainly been focused on pathogens. As a major component of the microbiome of the human intestinal tract, probiotics are important to keep the host healthy. Accordingly, understanding their changes under weightlessness conditions has substantial value. This study was carried out to investigate the characteristics of Lactobacillus acidophilus, a typical probiotic for humans, under simulated microgravity (SMG) conditions...
December 24, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28009872/medium-chain-fatty-acids-reduce-serum-cholesterol-by-regulating-the-metabolism-of-bile-acid-in-c57bl-6j-mice
#17
Yinghua Liu, Yong Zhang, Xinsheng Zhang, Qing Xu, Xueyan Yang, Changyong Xue
Hypercholesterolemia is one of the important risk factors of atherosclerosis (AS). The aim of this study is to explore the effect of medium-chain fatty acids (MCFAs) on serum cholesterol levels and their mechanism of action. Hyperlipemia, as a model of abnormal lipid hypermetabolism, was established by using a high fat diet in C57BL/6J mice. Forty eight mice with dyslipidemia were randomly divided into 4 groups, 12 mice per group, including the control group, the 2% caprylic acid (C8:0)-treated group, 2% capric acid (C10:0)-treated group, and 2% oleic acid (C18:1)-treated group...
December 23, 2016: Food & Function
https://www.readbyqxmd.com/read/28008998/impaired-hepatic-adaptation-to-chronic-cholestasis-induced-by-primary-sclerosing-cholangitis
#18
Malgorzata Milkiewicz, Marta Klak, Agnieszka Kempinska-Podhorodecka, Anna Wiechowska-Kozlowska, Elzbieta Urasinska, Malgorzata Blatkiewicz, Ewa Wunsch, Elwyn Elias, Piotr Milkiewicz
Pathogenesis of primary sclerosing cholangitis (PSC) may involve impaired bile acid (BA) homeostasis. We analyzed expressions of factors mediating enterohepatic circulation of BA using ileal and colonic (ascending and sigmoid) biopsies obtained from patients with PSC with and without ulcerative colitis (UC) and explanted PSC livers. Two-fold increase of BA-activated farnesoid X receptor (FXR) protein levels were seen in ascending and sigmoid colon of PSC patients with correspondingly decreased apical sodium-dependent BA transporter (ASBT) gene expression...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27988401/geniposide-attenuates-anit-induced-cholestasis-through-regulation-of-transporters-and-enzymes-involved-in-bile-acids-homeostasis-in-rats
#19
Lingling Wang, Guixin Wu, Feihua Wu, Nan Jiang, Yining Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Geniposide (GE) is one of the major iridoid glycosides isolated from the fruit of Gardenia jasminoides Ellis that has been used to treat hepatic disorders including cholestasis. However, the underlying mechanisms for GE ameliorating the reduction in bile acids accumulation by α-naphthylisothiocyanate (ANIT) remain unclear. AIM OF THE STUDY: The purpose of this study is to characterize the efficacy of GE in regulation of bile acids uptake, synthesis, metabolism, and transport in ANIT-induced rats...
January 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27981592/the-ascending-pathophysiology-of-cholestatic-liver-disease
#20
REVIEW
Peter L M Jansen, Ahmed Ghallab, Nachiket Vartak, Raymond Reif, Frank G Schaap, Jochen Hampe, Jan G Hengstler
In this review we develop the argument that cholestatic liver diseases, particularly primary biliary cholangitis and primary sclerosing cholangitis (PSC), evolve over time with anatomically an ascending course of the disease process. The first and early lesions are in "downstream" bile ducts. This eventually leads to cholestasis, and this causes bile salt (BS)-mediated toxic injury of the "upstream" liver parenchyma. BS are toxic in high concentration. These concentrations are present in the canalicular network, bile ducts, and gallbladder...
February 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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