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Liver X Receptor

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https://www.readbyqxmd.com/read/29045950/leonurine-prevents-atherosclerosis-via-promoting-the-expression-of-abca1-and-abcg1-in-a-ppar%C3%AE-lxr%C3%AE-signaling-pathway-dependent-manner
#1
Ting Jiang, Kun Ren, Qian Chen, Heng Li, Rong Yao, Hu Hu, Yun-Cheng Lv, Guo-Jun Zhao
BACKGROUND/AIMS: Previous studies have demonstrated that leonurine, a unique alkaloid compound of Herba leonuri, can exert anti-oxidative and anti-inflammatory effects on the development of atherosclerosis (AS). This study was designed to investigate the effects of leonurine on cholesterol efflux from THP-1 macrophage-derived foam cells and development of atherosclerotic lesions in apoE-/- mice, and further determine the potential mechanisms. METHODS: Human THP-1 cells were fully differentiated into foam cells by the pre-treatment with phorbol-12-myristate-13-acetate (PMA) and oxidized density lipoproteins (ox-LDL)...
October 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29042644/hiv-1-viral-protein-r-vpr-induces-fatty-liver-in-mice-via-lxr%C3%AE-and-ppar%C3%AE-dysregulation-implications-for-hiv-specific-pathogenesis-of-nafld
#2
Neeti Agarwal, Dinakar Iyer, Chiara Gabbi, Pradip Saha, Sanjeet G Patel, Qianxing Mo, Benny Chang, Biman Goswami, Ulrich Schubert, Jeffrey B Kopp, Dorothy E Lewis, Ashok Balasubramanyam
HIV patients develop hepatic steatosis. We investigated hepatic steatosis in transgenic mice expressing the HIV-1 accessory protein Vpr (Vpr-Tg) in liver and adipose tissues, and WT mice infused with synthetic Vpr. Vpr-Tg mice developed increased liver triglyceride content and elevated ALT, bilirubin and alkaline phosphatase due to three hepatic defects: 1.6-fold accelerated de novo lipogenesis (DNL), 45% slower fatty acid ß-oxidation, and 40% decreased VLDL-triglyceride export. Accelerated hepatic DNL was due to coactivation by Vpr of liver X receptor-α (LXRα) with increased expression of its lipogenic targets Srebp1c, Chrebp, Lpk, Dgat, Fasn and Scd1, and intranuclear SREBP1c and ChREBP...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024600/liver-x-receptor-%C3%AE-is-targeted-by-microrna-1-to-inhibit-cardiomyocyte-apoptosis-through-ros-mediated-mitochondrial-pathway
#3
Yongxia Cheng, Dawei Zhang, Min Zhu, Ying Wang, Sufen Guo, Biao Xu, Guangyu Hou, Yukuan Feng, Guibo Liu
Diabetic cardiomyopathy (DCM) is defined as ventricular dysfunction occurring independently of a recognized cause such as hypertension or coronary artery disease. Liver X receptor α (LXRα), a subtype of ligand-activated transcription factors LXRs, has been considered as a potential pharmacological target in the pathogenesis of cardiovascular and metabolic diseases. However, the potential mechanism of how LXRα is regulated in cardiomyocytes is still unclear. This study investigated the effect of activating LXRα with GW3965 on cardiomyocyte apoptosis and its upstream regulator in glucose-induced H9C2 cells...
October 12, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29018272/bile-acid-microbiota-crosstalk-in-gastrointestinal-inflammation-and-carcinogenesis
#4
REVIEW
Wei Jia, Guoxiang Xie, Weiping Jia
Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids, produced in the liver, are metabolized by enzymes derived from intestinal bacteria and are critically important for maintaining a healthy gut microbiota, balanced lipid and carbohydrate metabolism, insulin sensitivity and innate immunity. Given the complexity of bile acid signalling and the direct biochemical interactions between the gut microbiota and the host, a systems biology perspective is required to understand the liver-bile acid-microbiota axis and its role in gastrointestinal carcinogenesis to reverse the microbiota-mediated alterations in bile acid metabolism that occur in disease states...
October 11, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28993927/rhodium-ii-complex-with-2-benzoylpyridine-a-novel-potential-chemotherapeutic-drug-induces-cell-cycle-arrest-and-apoptosis-in-hepg2-cells
#5
Xuehong Wang, Yulan Li, Minglin Lin, Junfei Jin, Zhaoquan Huang
Rhodium (II) complex with 2-benzoylpyridine (Rh(L)2Cl2) is a new, synthetic, active metal-complex, which is produced by the reaction of 2-benzoylpyridine (L) with rhodium chloride hydrate (RhCl3·nH2O). The crystal structure was determined by X-ray diffraction which is mono-nuclear. In order to explore the biological properties of the novel complex, a series of studies were performed. The results showed that Rh(L)2Cl2 had the anti-tumor activity in HepG2 and other cell lines and has been shown to induce G1 cell cycle arrest and apoptosis in HepG2 cells...
October 9, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28993775/il-27-induced-type-1-regulatory-t-cells-produce-oxysterols-that-constrain-il-10-production
#6
Solenne Vigne, Fanny Chalmin, Donovan Duc, Aurélie S Clottu, Lionel Apetoh, Jean-Marc A Lobaccaro, Isabelle Christen, Juan Zhang, Caroline Pot
The behaviors of lymphocytes, including CD4(+) T helper cells, are controlled on many levels by internal metabolic properties. Lipid metabolites have recently been ascribed a novel function as immune response modulators and perturbation of steroids pathways modulates inflammation and potentially promotes a variety of diseases. However, the impact of lipid metabolism on autoimmune disease development and lymphocyte biology is still largely unraveled. In this line, oxysterols, oxidized forms of cholesterol, have pleiotropic roles on the immune response aside from their involvements in lipid metabolism...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28993270/reduced-silent-information-regulator-1-signaling-exacerbates-sepsis-induced-myocardial-injury-and-mitigates-the-protective-effect-of-a-liver-x-receptor-agonist
#7
Dong Han, Xiang Li, Shuang Li, Tao Su, Wen-Si Fan, Hong-Yu Qiao, Jiang-Wei Chen, Miao-Miao Fan, Xiu-Juan Li, Ya-Bin Wang, Sai Ma, Ya Qiu, Zu-Hong Tian, Feng Cao
Myocardial injury and dysfunction are critical manifestations of sepsis. Previous studies have reported that liver X receptor (LXR) activation is protective during sepsis. However, whether LXR activation protects against septic heart injury and its underlying mechanisms remain elusive. This study was designed to determine the role of LXR activation in the septic heart with a focus on SIRT1 (silent information regulator 1) signaling. Male cardiac-specific SIRT1 knockout mice (SIRT1-/-) and their wild-type littermates were subjected to sepsis by cecal ligation and puncture (CLP) in the presence or absence of LXR agonist T0901317...
October 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28993159/prevention-of-cholesterol-gallstone-disease-by-schaftoside-in-lithogenic-diet-induced-c57bl-6-mouse-model
#8
Meijing Liu, Changhui Liu, Hao Chen, Xiaotao Huang, Xiaohui Zeng, Juncheng Zhou, Suiqing Mi
Schaftoside (SS) is a bioactive compound present in the Herba Desmodii Styracifolii (DS), a herb that has been used to treat cholelithiasis and urolithiasis in Chinese medicine. Whether SS inhibits cholesterol (Ch) gallstone formation has not been investigated. This study examined the effects of oral intake of SS on Ch gallstone formation in C57BL/6 mice fed a lithogenic diet. The rate of gallstone formation was recorded. Levels of Ch, triglycerides (TG) and bile salts (BS) were measured in the bile and serum...
October 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28989932/mutations-in-liver-x-receptor-alpha-that-impair-dimerization-and-ligand-dependent-transactivation
#9
Shimpi Bedi, Heather A Hostetler, Stanley Dean Rider
Liver X receptor alpha (LXRα) is crucial for the maintenance of lipid and cholesterol homeostasis. Ligand binding and dimerization with retinoid X receptor (RXR) or peroxisome proliferator-activated receptor (PPAR) is required for forming active DNA binding complexes leading to gene regulation. Structure based prediction and solvent accessibility of LXRα LBD shows that residues H383, E387, H390, L414, and R415 which are located in helices 9 and 10 may be critical for mediating protein-protein interactions...
2017: Nuclear Receptor Research
https://www.readbyqxmd.com/read/28987596/computational-discovery-and-experimental-verification-of-farnesoid-x-receptor-agonist-auraptene-to-protect-against-cholestatic-liver-injury
#10
Xiaoguang Gao, Ting Fu, Changyuan Wang, Chenqing Ning, Yulong Kong, Zhihao Liu, Huijun Sun, Xiaodong Ma, Kexin Liu, Qiang Meng
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 novel therapeutic strategy against cholestasis. Herein, we used a novel computational strategy with two-dimensional virtual screening for FXR agonists. For the first time, we found that auraptene (AUR), a natural product, can activate FXR to exert hepatoprotective effect against cholestatic liver injury in vivo and in vitro. Importantly, AUR was found to significantly decrease the mortality of cholestatic mice...
October 4, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28986309/farnesoid-x-receptor-a-homeostat-for-hepatic-nutrient-metabolism
#11
REVIEW
Vittoria Massafra, Saskia van Mil
The Farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids (BAs). BAs are amphipathic molecules that serve as fat solubilizers in the intestine under postprandial conditions. In the post-absorptive state, BAs bind FXR in the hepatocytes, which in turn provides feedback signals on BA synthesis and transport and regulates lipid, glucose and amino acid metabolism. Therefore, FXR acts as a homeostat of all three classes of nutrients, fats, sugars and proteins. Here we re-analyze the function of FXR in the perspective of nutritional metabolism, and discuss the role of FXR in liver energy homeostasis in postprandial, post-absorptive and fasting/starvation states...
October 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28986308/n-3-fatty-acids-combined-with-flavan-3-ols-prevent-steatosis-and-liver-injury-in-a-murine-model-of-nafld
#12
David Vauzour, Ildefonso Rodriguez-Ramiro, Simon Rushbrook, Ignacio R Ipharraguerre, Damon Bevan, Susan Davies, Noemi Tejera, Pedro Mena, Sonia de Pascual-Teresa, Daniele Del Rio, Jelena Gavrilovic, Anne Marie Minihane
Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults and at present no licensed medication has been approved. Despite its complex patho-physiology, dietary strategies aiming at delaying or preventing NAFLD have taken a reductionist approach, examining the impact of single components. Accumulating evidence suggests that n-3 LC-PUFAs are efficacious in regulating lipogenesis and fatty acid oxidation. In addition, plant derived flavonoids are also emerging as a dietary strategy for NAFLD prevention, with efficacy attributed to their insulin sensitising and indirect antioxidant effects...
October 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28983452/role-of-fxr-in-liver-inflammation-during-nonalcoholic-steatohepatitis
#13
Laura E Armstrong, Grace L Guo
PURPOSE OF REVIEW: About 15-25% of patients with simple steatosis of non-alcoholic fatty liver disease progresses to non-alcoholic steatohepatitis (NASH), and the underlying mechanism for this progression has not been elucidated. NASH ultimately could progress to cirrhosis, an irreversible condition. RECENT FINDINGS: Farnesoid X receptor (FXR) has been studied for its role in modulating inflammation, and the expression of FXR is down-regulated during NASH development...
April 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28982861/liver-x-receptor-lxr-regulated-genes-of-cholesterol-trafficking-and-breast-cancer-severity
#14
COMPARATIVE STUDY
Christine Bobin-Dubigeon, Anaïs Chauvin, Victoire Brillaud-Meflah, Florence Boiffard, Marie-Pierre Joalland, Jean-Marie Bard
BACKGROUND: Liver X receptor [LXR; nuclear receptor subfamily 1, group H, member 2 (NR1H2, alias LXRB)] can inhibit proliferation and induce apoptosis of cancer cells. Its relationship with disease severity is not known. MATERIALS AND METHODS: Expression of LXRB, ATP binding cassette subfamily A member 1 (ABCA1), ATP binding cassette subfamily G member 1 (ABCG1), apolipoprotein E (APOE) and paraoxonase 2 (PON2) were determined in 69 breast tumors and were related to clinical stages of the disease and tumor characteristics, as well as time to recurrence...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28982586/molecular-cloning-and-characterization-of-farnesoid-x-receptor-from-large-yellow-croaker-larimichthys-crocea-and-the-effect-of-dietary-cdca-on-the-expression-of-inflammatory-genes-in-intestine-and-spleen
#15
Jianlong Du, Xiaojun Xiang, Yongnan Li, Renlei Ji, Hanlin Xu, Kangsen Mai, Qinghui Ai
In the present study, farnesoid X receptor (FXR) was cloned and characterized from liver of large yellow croaker (L crocea) and the effects of dietary chenodeoxycholic acid (CDCA), a nature ligand of FXR, on the inflammatory genes expression in the intestine and spleen of large yellow croaker were investigated. Multiple alignments showed that FXR of large yellow croaker contained highly conserved DNA-binding domain and ligand binding domain compared with other species. The subcellular localization analysis showed that FXR-GFP fusion protein could target to the nucleus in HEK 293t...
October 2, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28979073/glycosides-based-standardized-fenugreek-seed-extract-ameliorates-bleomycin-induced-liver-fibrosis-in-rats-via-modulation-of-endogenous-enzymes
#16
Amit D Kandhare, Subhash Laxmanrao Bodhankar, Vishwaraman Mohan, Prasad A Thakurdesai
BACKGROUND: Liver fibrosis a complex process of excess collagen deposition resulted in disturbance of hepatic cellar function. Glycosides based standardized fenugreek seed extract (SFSE-G) has potent anti-inflammatory, antioxidant, and anti-fibrotic properties. OBJECTIVE: The aim of this study is to evaluate the hepatoprotective potential of SFSE-G against bleomycin (BLM)-induced liver fibrosis in laboratory animals. MATERIALS AND METHODS: Sprague-Dawley rats (180-220 g) were assigned to various groups, namely, normal, sham, BLM control, SFSE-G (5, 10, 20, and 40 mg/kg, p...
July 2017: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28978315/resveratrol-enhances-anticancer-effects-of-paclitaxel-in-hepg2-human-liver-cancer-cells
#17
Qin Jiang, Manyi Yang, Zhan Qu, Jixiang Zhou, Qi Zhang
BACKGROUND: The aim of this in vitro study was to measure the enhanced anticancer effects of Res (resveratrol) on PA (paclitaxel) in HepG2 human liver cancer cells. METHODS: The MTT (thiazolyl blue tetrazolium bromide, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), flow cytometry, qPCR (real-time quantitative polymerase chain reaction) and western blot assay were used for cells growth inhibitory effects, cells apoptosis (DNA content of sub-G1), mRNA and protein expressions, respectively...
October 4, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28972541/camkii%C3%AE-suppresses-an-efferocytosis-pathway-in-macrophages-and-promotes-atherosclerotic-plaque-necrosis
#18
Amanda C Doran, Lale Ozcan, Bishuang Cai, Ze Zheng, Gabrielle Fredman, Christina C Rymond, Bernhard Dorweiler, Judith C Sluimer, Joanne Hsieh, George Kuriakose, Alan R Tall, Ira Tabas
Atherosclerosis is the underlying etiology of cardiovascular disease, the leading cause of death worldwide. Atherosclerosis is a heterogeneous disease in which only a small fraction of lesions lead to heart attack, stroke, or sudden cardiac death. A distinct type of plaque containing large necrotic cores with thin fibrous caps often precipitates these acute events. Here, we show that Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ) in macrophages plays a major role in the development of necrotic, thin-capped plaques...
October 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28971954/dbz-danshensu-bingpian-zhi-a-novel-natural-compound-derivative-attenuates-atherosclerosis-in-apolipoprotein-e-deficient-mice
#19
Jing Wang, Pengfei Xu, Xinni Xie, Jiao Li, Jun Zhang, Jialin Wang, Fan Hong, Jian Li, Youyi Zhang, Yao Song, Xiaohui Zheng, Yonggong Zhai
BACKGROUND: DBZ (Danshensu Bingpian Zhi), a synthetic derivative of a natural compound found in traditional Chinese medicine, has been reported to suppress lipopolysaccharide-induced macrophage activation and lipid accumulation in vitro. The aim of this study was to assess whether DBZ could attenuate atherosclerosis at early and advanced stages. METHODS AND RESULTS: The effects of DBZ on the development of atherosclerosis were studied using apolipoprotein E-deficient (apoE(-/-)) mice...
October 2, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28971895/dyslipidemia-alters-sperm-maturation-and-capacitation-in-lxr-null-mice
#20
Marjorie Whitfield, Rachel Guiton, Jeremie Rispal, Niyazi Acar, Ayhan Kocer, Joël R Drevet, Fabrice Saez
Lipid metabolism disorders (dyslipidemia) are causes of male infertility, but little is known about their impact on male gametes when considering post-testicular maturation events, given that studies concentrate most often on endocrine dysfunctions and testicular consequences. In this study, three-month-old wild type (wt) and Liver-X-Receptors knock out (Lxrα;β-/-) males were fed four weeks with a control or a lipid-enriched diet containing 1.25% cholesterol (High Cholesterol Diet - HCD). The HCD triggered a dyslipidemia leading to sperm post-testicular alterations and infertility...
October 2, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
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