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Bile acid metabolism

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https://www.readbyqxmd.com/read/28106531/preclinical-characterization-of-the-novel-hcv-ns3-protease-inhibitor-gs-9256
#1
Huiling Yang, Chris Yang, Yujin Wang, Gerry Rhodes, Margaret Robinson, Guofeng Cheng, Xiaoping Qi, Hongmei Mo, Yang Tian, Rowchanak Pakdaman, X Christopher Sheng, Choung U Kim, William E Delaney
BACKGROUND: GS-9256 is an inhibitor of hepatitis C virus (HCV) NS3 protease with a macrocyclic structure and novel phosphinic acid pharmacophore. METHODS: Key preclinical properties of GS-9256 including in vitro antiviral activity, cross-resistance, and pharmacokinetic properties were investigated in non-human species. RESULTS: In genotype (GT) 1b Huh-luc cells with a replicon encoding luciferase, GS-9256 had a mean EC50 value of 20.0 nM, with minimal cytotoxicity...
January 20, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28106337/in-vivo-metabolomic-interpretation-of-the-anti-obesity-effects-of-hyacinth-bean-dolichos-lablab-l-administration-in-high-fat-diet-mice
#2
Dong Ho Suh, Hye Won Lee, Eun Sung Jung, Digar Singh, Seung-Hyung Kim, Choong Hwan Lee
SCOPE: The esoteric anti-obesity effects of hyacinth bean (Dolichos lablab L) have largely remained unexplored. Herein, we investigated the anti-obesity mechanisms of hyacinth bean compared to milk thistle, a natural herb employed for ameliorating obesity-related diseases, using high fat-diet (HFD) fed mice towards unfolding the perplexing mechanisms. METHODS AND RESULTS: C57BL/6J mice were orally administered hyacinth bean (25 mg/kg/day) and milk thistle (100 mg/kg/day) for 9 weeks along with HFD...
January 20, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28105254/disease-monitoring-of-hepatocellular-carcinoma-through-metabolomics
#3
REVIEW
Asem I Fitian, Roniel Cabrera
We elucidate major pathways of hepatocarcinogenesis and accurate diagnostic metabolomic biomarkers of hepatocellular carcinoma (HCC) identified by contemporary HCC metabolomics studies, and delineate a model HCC metabolomics study design. A literature search was carried out on Pubmed for HCC metabolomics articles published in English. All relevant articles were accessed in full text. Major search terms included "HCC", "metabolomics", "metabolomics", "metabonomic" and "biomarkers". We extracted clinical and demographic data on all patients and consolidated the lead candidate biomarkers, pathways, and diagnostic performance of metabolomic expression patterns reported by all studies in tables...
January 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28103699/vitamin-d-alteration-associated-with-obesity-and-bariatric-surgery
#4
Eric Lespessailles, Hechmi Toumi
Obesity and severe obesity constitute growing serious health problems reaching epidemic proportion in most countries. Interactions and relationships between obesity and bone tissue and its metabolism are complex but are more and more studied and recognized. Obesity is associated with an altered hormonal profile including particularly bone-regulating hormones like vitamin D. Bariatric surgery procedures, thanks to their effectiveness to achieve therapeutic endpoints for comorbidities associated with obesity, have had an increasing success...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28101967/host-related-factors-explaining-interindividual-variability-of-carotenoid-bioavailability-and-tissue-concentrations-in-humans
#5
Torsten Bohn, Charles Desmarchelier, Lars O Dragsted, Charlotte S Nielsen, Wilhelm Stahl, Ralph Rühl, Jaap Keijer, Patrick Borel
Carotenoid dietary intake and their endogenous levels have been associated with a decreased risk of several chronic diseases. There are indications that carotenoid bioavailability depends, in addition to the food matrix, on host factors. These include diseases (e.g. colitis), life-style habits (e.g. smoking), gender and age, as well as genetic variations including single nucleotide polymorphisms that govern carotenoid metabolism. These are expected to explain interindividual differences that contribute to carotenoid uptake, distribution, metabolism and excretion, and therefore possibly also their association with disease risk...
January 19, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28099124/browning-of-white-adipose-tissue-lessons-from-experimental-models
#6
Thereza Cristina Lonzetti Bargut, Vanessa Souza-Mello, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
Beige or brite (brown-in-white) adipocytes are present in white adipose tissue (WAT) and have a white fat-like phenotype that when stimulated acquires a brown fat-like phenotype, leading to increased thermogenesis. This phenomenon is known as browning and is more likely to occur in subcutaneous fat depots. Browning involves the expression of many transcription factors, such as PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor (PPAR)-γ, and of uncoupling protein (UCP)-1, which is the hallmark of thermogenesis...
January 18, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28095889/evolution-of-gut-microbiota-composition-from-birth-to-24-weeks-in-the-infantmet-cohort
#7
Cian J Hill, Denise B Lynch, Kiera Murphy, Marynka Ulaszewska, Ian B Jeffery, Carol Anne O'Shea, Claire Watkins, Eugene Dempsey, Fulvio Mattivi, Kieran Touhy, R Paul Ross, C Anthony Ryan, Paul W O' Toole, Catherine Stanton
BACKGROUND: The gut is the most extensively studied niche of the human microbiome. The aim of this study was to characterise the initial gut microbiota development of a cohort of breastfed infants (n = 192) from 1 to 24 weeks of age. METHODS: V4-V5 region 16S rRNA amplicon Illumina sequencing and, in parallel, bacteriological culture. The metabolomic profile of infant urine at 4 weeks of age was also examined by LC-MS. RESULTS: Full-term (FT), spontaneous vaginally delivered (SVD) infants' microbiota remained stable at both phylum and genus levels during the 24-week period examined...
January 17, 2017: Microbiome
https://www.readbyqxmd.com/read/28095750/effects-of-pre-germinated-brown-rice-treatment-high-fat-diet-induced-metabolic-syndrome-in-c57bl-6j-mice
#8
Hsueh-Wei Yen, Hui-Li Lin, Chi-Long Hao, Fu-Chih Chen, Chun-Yun Chen, Jia-Hao Chen, Kuo-Ping Shen
To investigate using pre-germinated brown rice (PGBR) to treat metabolic syndrome, we fed one group of mice standard-regular-diet (SRD) for 20 weeks and another group of mice high-fat-diet (HFD) for 16 weeks. We subdivided them into HFD group and HFD + PGBR group whose dietary carbohydrate was replaced with PGBR for 4 weeks. The HFD group gained more weight, had higher blood pressure, heart rate, blood glucose and lipids, liver levels of TG, feces TG and bile acid, lower adipose levels of adipocytokine, lower skeletal muscle IR, IRS-1, IRS-2, PI3 K, Akt/PKB, GLUT-1, GLUT-4, GCK and PPAR-γ; higher liver SREBP-1, SCD-1, FAS, HMGCR, LDLR, CYP7α1 and PPAR-α, and higher adipose SREBP-1, SCD-1, FAS, and lower adipose PPAR-α and adiponectin...
January 18, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28095641/melatonin-ameliorates-alcohol-induced-bile-acid-synthesis-by-enhancing-mir-497-expression
#9
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/28093571/roux-en-y-gastric-bypass-increases-systemic-but-not-portal-bile-acid-concentrations-by-decreasing-hepatic-bile-acid-uptake-in-minipigs
#10
O Chávez-Talavera, G Baud, V Spinelli, M Daoudi, M Kouach, J-F Goossens, E Vallez, R Caiazzo, M Ghunaim, T Hubert, S Lestavel, A Tailleux, B Staels, F Pattou
Roux-en-Y gastric bypass (RYGB) surgery is widely used in the management of morbid obesity. RYGB improves metabolism independently of weight loss by still unknown mechanisms. Bile acids (BAs) are good candidates to explain this benefit, since they regulate metabolic homeostasis and their systemic concentrations increase upon RYGB. Here we analyzed the mechanisms underlying the increase in systemic BA concentrations after RYGB and the role of the liver therein. To this aim, we used the Göttingen-like minipig, a human-size mammalian model, which allows continuous sampling and simultaneous analysis of pre-hepatic portal and systemic venous blood...
January 17, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28092182/an-estrogen-receptor-%C3%AE-selective-agonist-inhibits-non-alcoholic-steatohepatitis-in-preclinical-models-by-regulating-bile-acid-and-xenobiotic-receptors
#11
Suriyan Ponnusamy, Quynh T Tran, Thirumagal Thiyagarajan, Duane D Miller, Dave Bridges, Ramesh Narayanan
Non-alcoholic steatohepatitis (NASH) affects 8-10 million people in the US and up to 75% of obese individuals. Despite this, there are no approved oral therapeutics to treat NASH and therefore the need for novel approaches exists. The estrogen receptor β (ER-β)-selective agonist, β-LGND2, inhibits body weight and white adipose tissue, and increases metabolism, resulting in higher energy expenditure and thermogenesis. Due to favorable effects of β-LGND2 on obesity, we hypothesized that β-LGND2 will prevent NASH directly by reducing lipid accumulation in the liver or indirectly by favorably changing body composition...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28091894/mechanisms-of-action-of-surgical-interventions-on-weight-related-diseases-the-potential-role-of-bile-acids
#12
REVIEW
Mohsen Mazidi, Pedro Paulo P de Caravatto, John R Speakman, Ricardo V Cohen
Surgical interventions for weight-related diseases (SWRD) may have substantial and sustainable effect on weight reduction, also leading to a higher remission rate of type 2 diabetes (T2D) mellitus than any other medical treatment or lifestyle intervention. The resolution of T2D after Roux-en-Y gastric bypass (RYGB) typically occurs too quickly to be accounted for by weight loss alone, suggesting that these operations have a direct impact on glucose homeostasis. The mechanisms underlying these beneficial effects however remain unclear...
January 14, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28087885/absence-of-intestinal-microbiota-increases-%C3%A3-cyclodextrin-stimulated-reverse-cholesterol-transport
#13
Rima H Mistry, Henkjan J Verkade, Uwe J F Tietge
SCOPE: Non-digestible oligosaccharides are used as prebiotics for perceived health benefits, among these modulating lipid metabolism. However, the mechanisms of action are incompletely understood. The present study characterized the impact of dietary ß-cyclodextrin (ßCD, 10%, w/w), a cyclic oligosaccharide, on sterol metabolism and reverse cholesterol transport (RCT) in conventional and also germ-free mice to establish dependency on metabolism by intestinal bacteria. METHODS AND RESULTS: In conventional ßCD-fed C57BL/6J wild-type mice plasma cholesterol decreased significantly (-40%, p<0...
January 14, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28086815/antibiotics-induced-depletion-of-mice-microbiota-induces-changes-in-host-serotonin-biosynthesis-and-intestinal-motility
#14
Xiaolong Ge, Chao Ding, Wei Zhao, Lizhi Xu, Hongliang Tian, Jianfeng Gong, Minsheng Zhu, Jieshou Li, Ning Li
BACKGROUND: The gastrointestinal motility is affected by gut microbiota and the relationship between them has become a hot topic. However, mechanisms of microbiota in regulating motility have not been well defined. We thus investigated the effect of microbiota depletion by antibiotics on gastrointestinal motility, colonic serotonin levels, and bile acids metabolism. METHODS: After 4 weeks with antibiotics treatments, gastrointestinal and colon transit, defecation frequency, water content, and other fecal parameters were measured and analyzed in both wild-type and antibiotics-treated mice, respectively...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28077274/the-role-and-regulation-of-the-peroxisome-proliferator-activated-receptor-alpha-in-human-liver
#15
REVIEW
Sander Kersten, Rinke Stienstra
The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is abundantly expressed in liver. PPARα is activated by fatty acids and various other lipid species, as well as by a class of chemicals referred to as peroxisome proliferators. Studies in mice have shown that PPARα serves as the master regulator of hepatic lipid metabolism during fasting. In addition, PPARα suppresses inflammation and the acute phase response. Comparatively little is known about PPARα in human liver...
January 7, 2017: Biochimie
https://www.readbyqxmd.com/read/28074537/neuroblastoma-causes-alterations-of-the-intestinal-microbiome-gut-hormones-inflammatory-cytokines-and-bile-acid-composition
#16
Christoph Castellani, Georg Singer, Margarita Kaiser, Thomas Kaiser, Jianfeng Huang, Daniela Sperl, Karl Kashofer, Guenter Fauler, Barbara Guertl-Lackner, Gerald Höfler, Holger Till
OBJECTIVE: To assess the effect of neuroblastoma (NB) on the intestinal microbiome, metabolism, and inflammatory parameters in a murine model. MATERIALS AND METHODS: Athymic Hsd:Fox1nu mice received subperitoneal implantation of human NB cells (MHH-NB11) (tumor group, TG) or culture medium (sham group). Following 10 weeks of tumor growth, all animals were sacrificed to collect total white adipose tissue (WAT). Luminex assays were performed for gut hormone and inflammation marker analysis...
January 11, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28062491/reverse-cholesterol-transport-is-increased-in-germ-free-mice
#17
Rima H Mistry, Henkjan J Verkade, Uwe J F Tietge
OBJECTIVE: The intestinal microbiota is emerging as a clinically relevant modulator of atherosclerotic risk. Reverse cholesterol transport (RCT) is an atheroprotective metabolic pathway. How the microbiota impacts RCT has not been investigated. Therefore, the aim of this study was to characterize cholesterol metabolism and RCT in germ-free mice compared with conventional mice. APPROACH AND RESULTS: In chow-fed germ-free mice, plasma cholesterol was unchanged, whereas liver cholesterol content was higher (1...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28059425/metabolic-profiling-of-a-myalgic-encephalomyelitis-chronic-fatigue-syndrome-discovery-cohort-reveals-disturbances-in-fatty-acid-and-lipid-metabolism
#18
Arnaud Germain, David Ruppert, Susan M Levine, Maureen R Hanson
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remains a continuum spectrum disease without biomarkers or simple objective tests, and therefore relies on a diagnosis from a set of symptoms to link the assortment of brain and body disorders to ME/CFS. Although recent studies show various affected pathways, the underlying basis of ME/CFS has yet to be established. In this pilot study, we compare plasma metabolic signatures in a discovery cohort, 17 patients and 15 matched controls, and explore potential metabolic perturbations as the aftermath of the complex interactions between genes, transcripts and proteins...
January 6, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28041926/chronic-over-expression-of-fibroblast-growth-factor-21-increases-bile-acid-biosynthesis-by-opposing-fgf15-19-action
#19
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
#20
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
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