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Bile acid metabolism

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https://www.readbyqxmd.com/read/29666185/hepatocyte-nuclear-receptor-shp-suppresses-inflammation-and-fibrosis-in-a-mouse-model-of-nonalcoholic-steatohepatitis
#1
An Zou, Nancy Magee, Fengyan Deng, Sarah Lehn, Cuncong Zhong, Yuxia Zhang
Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide, ranging from nonalcoholic fatty liver (NAFL, steatosis without hepatocellular injury) to the more aggressive nonalcoholic steatohepatitis (NASH, steatosis with ballooning, inflammation, or fibrosis). Although many studies have greatly contributed to the elucidation of NAFLD pathogenesis, the disease progression from NAFL to NASH still remains incompletely understood. Nuclear receptor small heterodimer partner (Nr0b2, SHP) is a transcriptional regulator critical for the regulation of bile acid, glucose, and lipid metabolism...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29665623/dietary-mannan-oligosaccharides-modulate-gut-microbiota-increase-fecal-bile-acid-excretion-and-decrease-plasma-cholesterol-and-atherosclerosis-development
#2
Lisa R Hoving, Saeed Katiraei, Marieke Heijink, Amanda Pronk, Lianne van der Wee-Pals, Trea Streefland, Martin Giera, Ko Willems van Dijk, Vanessa van Harmelen
SCOPE: Mannan oligosaccharides (MOS) have proven effective at improving growth performance, while also reducing hyperlipidemia and inflammation. As atherosclerosis is accelerated both by hyperlipidemia and inflammation, we aimed to determine the effect of dietary MOS on atherosclerosis development in hyperlipidemic ApoE*3-Leiden.CETP (E3L.CETP) mice, a well-established model for human-like lipoprotein metabolism. METHODS AND RESULTS: Female E3L.CETP mice were fed a high cholesterol diet, with or without 1% MOS for 14 weeks...
April 17, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29664215/the-plasma-bile-acid-alterations-of-type-2-diabetes-correlated-with-insulin-secretion-in-two-step-hyperglycemic-clamp
#3
Shujie Wang, Yuying Deng, Xiaoyan Xie, Jing Ma, Min Xu, Xinjie Zhao, Weiqiong Gu, Jie Hong, Weiqing Wang, Guowang Xu, Guang Ning, Yanyun Gu, Yifei Zhang
BACKGROUND: Bile acids (BAs) conduct crucial signals in human metabolism. Correlations between human plasma BA alterations and insulin secretion defects and type 2 diabetes (T2D) progression have been insufficiently studied. This study was performed to explore the trajectories of human plasma BA alterations and their association with the insulin secretion dynamics during a two-step hyperglycemic clamp. METHODS: Eleven healthy (NGT) and 33 drug-naïve T2D subjects (T2Ds) were enrolled to undertake a two-step hyperglycemic clamp...
April 17, 2018: Journal of Diabetes
https://www.readbyqxmd.com/read/29663642/oral-administration-of-edible-wakame-seaweed-undaria-pinnatifida-wakame-modifies-glucose-and-lipid-metabolism-in-rats-a-dna-microarray-analysis
#4
Keiko Yoshinaga, Yuji Nakai, Hikari Izumi, Kaz Nagaosa, Tomoko Ishijima, Takahisa Nakano, Keiko Abe
SCOPE: Wakame is an edible seaweed that is a common constituent in the Japanese diet. Previous studies showed that wakame consumption is associated with the prevention of metabolic syndrome, but the molecular mechanisms underlying the protective effects are poorly understood. METHODS AND RESULTS: To determine if the expression of hepatic genes is affected by ingestion of the brown seaweed Undaria pinnatifida (wakame), rats were fed a diet containing 0, 0.1, or 1...
April 16, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29662454/the-biological-clock-a-pivotal-hub-in-non-alcoholic-fatty-liver-disease-pathogenesis
#5
REVIEW
Gianluigi Mazzoccoli, Salvatore De Cosmo, Tommaso Mazza
Non-alcoholic fatty liver disease (NAFLD) is the most frequent hepatic pathology in the Western world and may evolve into steatohepatitis (NASH), increasing the risk of cirrhosis, portal hypertension and hepatocellular carcinoma. NAFLD derives from the accumulation of hepatic fat due to discrepant free fatty acid metabolism. Other factors contributing to this are deranged nutrients and bile acids fluxes as well as alterations in nuclear receptors, hormones, and intermediary metabolites, which impact on signaling pathways involved in metabolism and inflammation...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29660435/yangonin-protects-against-cholestasis-and-hepatotoxity-via-activation-of-farnesoid-x-receptor-in-vivo-and-in-vitro
#6
Xiaoguang Gao, Ting Fu, Changyuan Wang, Chenqing Ning, Kexin Liu, Zhihao Liu, Huijun Sun, Xiaodong Ma, Xiaokui Huo, Xiaobo Yang, Ming Zou, Qiang Meng
Cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Recently obeticholic acid (OCA) which is a farnesoid X receptor (FXR) agonist was approved by FDA to treat cholestatic liver diseases, which provided us a newly therapeutic strategy against cholestasis. The purpose of the current study is to screen novel FXR agonists and verify the anti-cholestasis effect of yangonin in vivo and in vitro. The computational strategy of two-dimensional virtual screening was used to search for new FXR agonists, and dual-luciferase reporter gene assay was used to further demonstrate FXR activation by yangonin...
April 13, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29660405/microbiome-mediated-bile-acid-modification-role-in-intestinal-drug-absorption-and-metabolism
#7
REVIEW
Elaine F Enright, Brendan T Griffin, Cormac G M Gahan, Susan A Joyce
Once regarded obscure and underappreciated, the gut microbiota (the microbial communities colonizing the gastrointestinal tract) is gaining recognition as an influencer of many aspects of human health. Also increasingly apparent is the breadth of interindividual variation in these co-evolved microbial-gut associations, presenting novel quests to explore implications for disease and therapeutic response. In this respect, the unearthing of the drug-metabolizing capacity of the microbiota has provided impetus for the integration of microbiological and pharmacological research...
April 13, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29660230/the-use-of-antimicrobials-as-adjuvant-therapy-for-the-treatment-of-obesity-and-insulin-resistance-effects-and-associated-mechanisms
#8
REVIEW
Sandra Aparecida Dos Reis, Maria do Carmo Gouveia Peluzio, Josefina Bressan
The intestinal microbiota has come to be considered an additional risk factor for the development of metabolic diseases. Considering the potential role of antimicrobials as modulators of the intestinal microbiota, they have been investigated for use in the adjuvant treatment of obesity and insulin resistance. In this regard, the present manuscript aimed to review the effect of regular use of antimicrobials on the treatment of obesity and/or IR, as well as its associated mechanisms. The regular use of antimicrobials does not seem to influence the body weight and adiposity of its consumer...
April 16, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29659898/cholesterol-metabolism-is-enhanced-in-the-liver-and-brain-of-children-with-citrin-deficiency
#9
Satoshi Hirayama, Hironori Nagasaka, Akira Honda, Haruki Komatsu, Takahiro Kodama, Ayano Inui, Ichiro Morioka, Shunsaku Kaji, Tsuyoshi Ueno, Kenji Ihara, Mariko Yagi, Zenro Kizaki, Kazuhiko Bessho, Hiroki Kondou, Tohru Yorifuji, Hirokazu Tsukahara, Kazumoto Iijima, Takashi Miida
Context: Citrin-deficient infants present neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), which resolves at 12 months. Thereafter, they have normal liver function associated with hypercholesterolemia, and a preference for lipid-rich carbohydrate-restricted diets. However, some develop adult-onset type II citrullinemia (CTLN2), which is associated with metabolic abnormalities. Objectives: To identify the causes of hypercholesterolemia in citrin-deficient children post-NICCD...
April 5, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29658451/-clinical-and-genetic-analysis-of-a-pediatric-patient-with-sodium-taurocholate-cotransporting-polypeptide-deficiency
#10
Hua Li, Jian-Wu Qiu, Gui-Zhi Lin, Mei Deng, Wei-Xia Lin, Ying Cheng, Yuan-Zong Song
Sodium taurocholate cotransporting polypeptide (NTCP) deficiency is an inborn error of bile acid metabolism caused by mutations of SLC10A1 gene. This paper reports the clinical and genetic features of a patient with this disease. A 3.3-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 3 months. Physical examination revealed moderate jaundice of the skin and sclera. The liver was palpable 3.5 cm below the right subcostal margin with a medium texture. Serum biochemistry analysis revealed markedly elevated bilirubin (predominantly direct bilirubin) and total bile acids (TBA), as well as decreased 25-OH-VitD level...
April 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29657561/habitual-sleep-and-human-plasma-metabolomics
#11
Qian Xiao, Andriy Derkach, Steven C Moore, Wei Zheng, Xiao-Ou Shu, Fangyi Gu, Neil E Caporaso, Joshua N Sampson, Charles E Matthews
Introduction: Sleep plays an important role in cardiometabolic health. The sleep-wake cycle is partially driven by the endogenous circadian clock, which governs a range of metabolic pathways. The association between sleep and cardiometabolic health may be mediated by alterations of the human metabolome. Objectives: To better understand the biological mechanism underlying the association between sleep and health, we examined human plasma metabolites in relation to sleep duration and sleep timing...
May 2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/29656109/bile-acids-are-important-direct-and-indirect-regulators-of-the-secretion-of-appetite-and-metabolism-regulating-hormones-from-the-gut-and-pancreas
#12
Rune E Kuhre, Nicolai J Wewer Albrechtsen, Olav Larsen, Sara L Jepsen, Emilie Balk-Møller, Daniel B Andersen, Carolyn F Deacon, Kristina Schoonjans, Frank Reimann, Fiona M Gribble, Reidar Albrechtsen, Bolette Hartmann, Mette M Rosenkilde, Jens J Holst
OBJECTIVE: Bile acids (BAs) facilitate fat absorption and may play a role in glucose and metabolism regulation, stimulating the secretion of gut hormones. The relative importance and mechanisms involved in BA-stimulated secretion of appetite and metabolism regulating hormones from the gut and pancreas is not well described and was the purpose of this study. METHODS: The effects of bile acids on the secretion of gut and pancreatic hormones was studied in rats and compared to the most well described nutritional secretagogue: glucose...
March 17, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29655695/alisma-orientale-extract-exerts-the-reversing-cholestasis-effect-by-activation-of-farnesoid-x-receptor
#13
Xiao-Kui Huo, Jing Liu, Zhen-Long Yu, Yi-Fei Wang, Chao Wang, Xiang-Ge Tian, Jing Ning, Lei Feng, Cheng-Peng Sun, Bao-Jing Zhang, Xiao-Chi Ma
BACKGROUND: Cholestasis is a clinical syndrome of liver damage that is caused by accumulation of bile acids in the liver and systemic circulation. Farnesoid X receptor (FXR) can regulate synthesis, metabolism, and excretion of bile acids. The rhizomes of Alisma orientale is a well-known traditional Chinese medicine to treat edema, obesity, gonorrhea, leukorrhea, diarrhea, hyperlipidemia, and diabetes in China. HYPOTHESIS/PURPOSE: We hypothesized Alisma orientale extract (AOE) to exert hepatoprotective effect against α-naphthylisothiocyanate (ANIT) induced cholestasis in rat...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29653253/cholesterol-and-bile-acid-mediated-regulation-of-autophagy-in-fatty-liver-diseases-and-atherosclerosis
#14
REVIEW
Yifeng Wang, Wen-Xing Ding, Tiangang Li
Liver is the major organ that regulates whole body cholesterol metabolism. Disrupted hepatic cholesterol homeostasis contributes to the pathogenesis of nonalcoholic steatohepatitis, dyslipidemia, atherosclerosis, and cardiovascular diseases. Hepatic bile acid synthesis is the major catabolic mechanism for cholesterol elimination from the body. Furthermore, bile acids are signaling molecules that regulate liver metabolism and inflammation. Autophagy is a highly-conserved lysosomal degradation mechanism, which plays an essential role in maintaining cellular integrity and energy homeostasis...
April 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29651702/tsumura-suzuki-obese-diabetic-mice-derived-hepatic-tumors-closely-resemble-human-hepatocellular-carcinomas-in-metabolism-related-genes-expression-and-bile-acid-accumulation
#15
Tetsuyuki Takahashi, Ulrich Deuschle, Shu Taira, Takeshi Nishida, Makoto Fujimoto, Takao Hijikata, Koichi Tsuneyama
BACKGROUND AND AIMS: Tsumura-Suzuki obese diabetic (TSOD) is a good model of metabolic syndrome showing typical lesions found in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and develops spontaneous hepatic tumors with a high frequency. Majority of the developing tumors overexpress glutamine synthetase (GS), which is used as a marker of hepatocellular carcinoma (HCC). The aim of this study is to assess the status of expression of metabolism-related genes and the level of bile acids in the TSOD mice-derived tumors and to determine the association with metabolic dysregulation between human HCC and TSOD mice-derived tumors...
April 12, 2018: Hepatology International
https://www.readbyqxmd.com/read/29651202/a-narrative-review-of-potential-future-antidiabetic-drugs-should-we-expect-more
#16
REVIEW
Gaurav Chikara, Pramod Kumar Sharma, Pradeep Dwivedi, Jaykaran Charan, Sneha Ambwani, Surjit Singh
Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential...
April 2018: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/29651010/dietary-supplementation-with-flaxseed-meal-and-oat-hulls-modulates-intestinal-histomorphometric-characteristics-digesta-and-mucosa-associated-microbiota-in-pigs
#17
S P Ndou, H M Tun, E Kiarie, M C Walsh, E Khafipour, C M Nyachoti
The establishment of a healthy gastrointestinal milieu may not only offer an opportunity to reduce swine production costs but could also open the way for a lifetime of human health improvement. This study investigates the effects of feeding soluble fibre from flaxseed meal-containing diet (FM) and insoluble fibre from oat hulls-containing diet (OH) on histomorphological characteristics, digesta- and mucosa-associated microbiota and their associations with metabolites in pig intestines. In comparison with the control (CON) and OH diets, the consumption of FM increased (P < 0...
April 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29649907/farnesoid-x-receptor-modulators-2014-present-a-patent-review
#18
Valentina Sepe, Eleonora Distrutti, Stefano Fiorucci, Angela Zampella
The nuclear receptor FXR regulates the expression of genes involved in bile acids, glucose and lipid homeostasis. For its role as guardian of metabolism, FXR has been identified a promising pharmacological target in liver bile acid and lipid accumulation, such as cholestasis and non-alcoholic fatty liver disease (NAFLD). The field of FXR research is extremely competitive with a large number of patents and articles published in the last decades identifying promising hit compounds. Areas covered. The present review summarizes recent patent activity (2014-to date) filing for synthetic and natural FXR ligands, including bile acid derivatives and non-steroidal compounds, alongside their in vitro and in vivo efficacy as well as their therapeutic applications...
April 13, 2018: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29644395/metabolic-phenotyping-of-malnutrition-during-the-first-1000-days-of-life
#19
REVIEW
Jordi Mayneris-Perxachs, Jonathan R Swann
Nutritional restrictions during the first 1000 days of life can impair or delay the physical and cognitive development of the individual and have long-term consequences for their health. Metabolic phenotyping (metabolomics/metabonomics) simultaneously measures a diverse range of low molecular weight metabolites in a sample providing a comprehensive assessment of the individual's biochemical status. There are a growing number of studies applying such approaches to characterize the metabolic derangements induced by various forms of early-life malnutrition...
April 11, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29626102/identification-of-unusual-oxysterols-and-bile-acids-with-7-oxo-or-3%C3%AE-5%C3%AE-6%C3%AE-trihydroxy-functions-in-human-plasma-by-charge-tagging-mass-spectrometry-with-multistage-fragmentation
#20
William J Griffiths, Ian Gilmore, Eylan Yutuc, Jonas Abdel-Khalik, Peter J Crick, Thomas Hearn, Alison Dickson, Brian W Bigger, Teresa Hoi-Yee Wu, Anu Goenka, Arunabha Ghosh, Simon A Jones, Yuqin Wang
7-Oxocholesterol (7-OC), 5,6-epoxycholesterol (5,6-EC) and its hydrolysis product cholestane-3β,5α,6β-triol (3β,5α,6β-triol) are normally minor oxysterols in human samples, however, in disease their levels may be greatly elevated. This is the case in plasma from patients suffering from some lysosomal storage disorders e.g. Niemann Pick disease type C, or the inborn errors of sterol metabolism e.g. Smith-Lemli-Opitz syndrome and cerebrotendinous xanthomatosis. A complication in the analysis of 7-OC and 5,6-EC is that they can also be formed ex vivo from cholesterol during sample handling in air causing confusion with molecules formed in vivo...
April 6, 2018: Journal of Lipid Research
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