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Liver X Receptor

Demin Cai, Mengjie Yuan, Haoyu Liu, Shifeng Pan, Wenqiang Ma, Jian Hong, Ruqian Zhao
Betaine serves as an animal and human nutrient which has been heavily investigated in glucose and lipid metabolic regulation, yet the underlying mechanisms are still elusive. In this study, feeding sows with betaine-supplemented diets during pregnancy and lactation increased cholesterol content and low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI) gene expression, but decreasing bile acids content and cholesterol-7a-hydroxylase (CYP7a1) expression in the liver of weaning piglets...
October 18, 2016: Nutrients
Corneille Edgar Ontsouka, Xiao Huang, Eldar Aliyev, Christiane Albrecht
Cell-based studies previously showed that the ATP-binding cassette transporter A1 (ABCA1) transfers cholesterol across mammary epithelial cells (MEC). Data for phospholipid transport are lacking, and it is unclear from which cellular source the transported cholesterol stems, whether this transport activates signaling pathways, and how lactogenic hormones regulate it. To clarify these aspects, lipid transport and expressional analyses were performed in bovine primary (bMEC) and/or immortalized (MAC-T) MEC cultures...
October 16, 2016: Molecular and Cellular Endocrinology
X M Chen, F Q Li, S Yan, X C Wu, C L Tang
OBJECTIVE: To investigate the anti-inflammation effects by activation of the cholinergic anti-inflammatory pathway and its mechanisms in non-alcoholic steatohepatitis (NASH) model mice. METHODS: 6-week-old male C57BL/6J (B6) mice were randomly divided into four groups: the first group was normal mice, injected with saline; the second group was normal mice, injected with nicotine; the third group was NASH model mice, injected with saline; the fourth group was NASH model mice, injected with nicotine...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Carrie J Finno, Matthew H Bordbari, Stephanie J Valberg, David Lee, Josi Herron, Kelly Hines, Tamer Monsour, Erica Scott, Danika L Bannasch, James Mickelson, Libin Xu
Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are not present with eNAD and the molecular basis remains unknown. Given the neuropathologic phenotypic similarity of the conditions, we assessed the molecular basis of eNAD by global transcriptome sequencing of the cervical spinal cord...
October 14, 2016: Free Radical Biology & Medicine
Mariola Kurowska-Stolarska, Manhl K Hasoo, David J Welsh, Lynn Stewart, Donna McIntyre, Brian E Morton, Steven Johnstone, Ashley M Miller, Darren L Asquith, Neal L Millar, Ann B Millar, Carol A Feghali-Bostwick, Nikhil Hirani, Peter J Crick, Yuqin Wang, William J Griffiths, Iain B McInnes, Charles McSharry
BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF therefore microRNAs may reveal novel pathogenic pathways. OBJECTIVES: To determine the regulatory role of microRNA(miR)-155 in the pro-fibrotic function of murine lung macrophages and fibroblasts, IPF lung fibroblasts and its contribution to experimental pulmonary fibrosis...
October 13, 2016: Journal of Allergy and Clinical Immunology
Genaro R Villa, Jonathan J Hulce, Ciro Zanca, Junfeng Bi, Shiro Ikegami, Gabrielle L Cahill, Yuchao Gu, Kenneth M Lum, Kenta Masui, Huijun Yang, Xin Rong, Cynthia Hong, Kristen M Turner, Feng Liu, Gary C Hon, David Jenkins, Michael Martini, Aaron M Armando, Oswald Quehenberger, Timothy F Cloughesy, Frank B Furnari, Webster K Cavenee, Peter Tontonoz, Timothy C Gahman, Andrew K Shiau, Benjamin F Cravatt, Paul S Mischel
Small-molecule inhibitors targeting growth factor receptors have failed to show efficacy for brain cancers, potentially due to their inability to achieve sufficient drug levels in the CNS. Targeting non-oncogene tumor co-dependencies provides an alternative approach, particularly if drugs with high brain penetration can be identified. Here we demonstrate that the highly lethal brain cancer glioblastoma (GBM) is remarkably dependent on cholesterol for survival, rendering these tumors sensitive to Liver X receptor (LXR) agonist-dependent cell death...
October 13, 2016: Cancer Cell
Xiaojiaoyang Li, Zihang Yuan, Runping Liu, Hozeifa M Hassan, Hang Yang, Rong Sun, Luyong Zhang, Zhenzhou Jiang
Estrogen-induced cholestasis, known as intrahepatic cholestasis of pregnancy (ICP), is an estrogen-related liver disease that is widely recognized as female or pregnancy-specific. Our previous findings showed that the synthetic estrogen, 17α-ethinylestradiol (EE), induced cholestatic injury through ERK1/2-LKB1-AMP-activated protein kinase (AMPK) signaling pathway and its mediated suppression of farnesoid X receptor (FXR). To investigate the role played by bile acids in EE-induced cholestasis, we evaluated the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) on sandwich cultured rat primary hepatocytes (SCRHs) and an in vivo rat model...
October 12, 2016: Toxicology and Applied Pharmacology
J E Edwards, C LaCerte, T Peyret, N H Gosselin, J F Marier, A F Hofmann, D Shapiro
Obeticholic acid (OCA), a semisynthetic bile acid, is a selective and potent farnesoid X receptor (FXR) agonist in development for the treatment of chronic nonviral liver diseases. Physiologic pharmacokinetic models have been previously used to describe the absorption, distribution, metabolism, and excretion (ADME) of bile acids. OCA plasma levels were measured in healthy volunteers and cirrhotic subjects. A physiologic pharmacokinetic model was developed to quantitatively describe the ADME of OCA in patients with and without hepatic impairment...
October 15, 2016: Clinical and Translational Science
Tiantian Luo, Jing Hu, Dan Xi, Haowei Xiong, Wenshuai He, Jichen Liu, Menghao Li, Hao Lu, Jinzhen Zhao, Wenyan Lai, Zhigang Guo
Previously, we reported that heat shock protein (HSP)65 impairs the effects of high-density lipoprotein on macrophages. We also showed that immune response activation adversely affects reverse cholesterol transport (RCT). In this study, we investigated the effects of the Src family kinase lymphocyte-specific protein tyrosine kinase (Lck) and elucidated the mechanism underlying HSP65-regulated cholesterol efflux in T cells. We evaluated cell proliferation, Lck expression, and inflammatory cytokine production in Jurkat cells and CD4(+) T cells...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Gu-Choul Shin, Hong Seok Kang, Ah Ram Lee, Kyun-Hwan Kim
Death receptors of TNFSF10/TRAIL (tumor necrosis factor superfamily member 10) contribute to immune surveillance against virus-infected or transformed cells by promoting apoptosis. Many viruses evade antiviral immunity by modulating TNFSF10 receptor signaling, leading to persistent infection. Here, we report that hepatitis B virus (HBV) X protein (HBx) restricts TNFSF10 receptor signaling via macroautophagy/autophagy-mediated degradation of TNFRSF10B/DR5, a TNFSF10 death receptor, and thus permits survival of virus-infected cells...
October 14, 2016: Autophagy
Jabadurai Jayapaul, Susanne Arns, Matt Bunker, Marek Weiler, Sandra Rutherford, Peter Comba, Fabian Kiessling
: Riboflavin (Rf) receptors bind and translocate Rf and its phosphorylated forms (e.g. flavin mononucleotide, FMN) into cells where they mediate various cellular metabolic pathways. Previously, we showed that FMN-coated ultrasmall superparamagnetic iron oxide (FLUSPIO) nanoparticles are suitable for labeling metabolically active cancer and endothelial cells in vitro. In this study, we focused on the in vivo application of FLUSPIO using prostate cancer xenografts. Size, charge, and chemical composition of FLUSPIO were evaluated...
2016: Nano Research
Jing Wang, Xing Dong, Hong-Yan Wu, Nan Wu, Xue-Jun Zhang, Xin Wang, Li-Xin Shang
BACKGROUND: Liver X receptor alpha (LXRα) and endoglin have been postulated to play roles in trophoblast invasion and lipid metabolic disturbances. However, the relationship between LXRα and endoglin levels in serum and placenta of patients with preeclampsia remains poorly understood. The objective of this study was to identify correlations between LXRα, endoglin and preeclampsia and provide new feasible methods of clinical prediction and treatment for preeclampsia. METHODS: We enrolled 45 patients with preeclampsia (24 with moderate preeclampsia and 21 with severe preeclampsia) and 15 normal pregnant women (control group) who were admitted to the Department of Obstetrics of the General Hospital of Beijing Command between October 2012 and July 2013 in this study...
2016: PloS One
Y Li, C G Zhang, X-H Wang, D-H Liu
OBJECTIVE: To construct the atherosclerosis model of ApoE-knockout (ApoE-/-) mouse after deposition of high-fat diet at brachiocephalic artery and coronary artery. MATERIALS AND METHODS: 40 healthy 8-week SPF-level male ApoE-/- mice of body weigh 16 to 23 g were averagely divided into a high-fat diet group and an ordinary diet group. Mice were sacrificed in a time course study by 3 months, 6 months, 9 months and 12 months. The brachiocephalic artery and coronary artery were extracted for pathological examination, and enzyme-linked immunosorbent assay (ELISA) was used for the examination of serum high-sensitivity C-reactive protein (hs-CRP) content and the relative expression level of liver peroxisome proliferator activated receptor (PPAR)...
September 2016: European Review for Medical and Pharmacological Sciences
Y Lu, Y-P Jia
OBJECTIVE: Quercetin has been reported to have the activities of antioxidant, anti-inflammatory, anti-virus, anti-cancer and so on. Many studies showed that quercetin could lower blood pressure and improve blood capillary elasticity, and it can also reduce LDL oxidation and prevent atherosclerosis. Although quercetin has been recognized to have the function of preventing atherosclerosis, little is known about its underlying mechanism. In this study, we try to explore whether quercetin up-regulates LXRa-mediated ABCA1 expression...
September 2016: European Review for Medical and Pharmacological Sciences
Ming Gu, Ping Zhao, Jinwen Huang, Yuanyuan Zhao, Yahui Wang, Yin Li, Yifei Li, Shengjie Fan, Yue-Ming Ma, Qingchun Tong, Li Yang, Guang Ji, Cheng Huang
Background and purpose: Silymarin, a standardized extract of the milk thistle seeds, has been widely used to treat chronic hepatitis, cirrhosis, and other types of toxic liver damage. Despite increasing studies on the action of silymarin and its major active constituent, silybin in their therapeutic properties against insulin resistance, diabetes and hyperlipidaemia in vitro and in vivo, the mechanism underlying silymarin action remains unclear. Experimental approach: C57BL/6 mice were fed high-fat diet (HFD) for 3 months to induce obesity, insulin resistance, hyperlipidaemia, and fatty liver...
2016: Frontiers in Pharmacology
Tetsuya Kimura, Shigeyuki Nada, Noriko Takegahara, Tatsusada Okuno, Satoshi Nojima, Sujin Kang, Daisuke Ito, Keiko Morimoto, Takashi Hosokawa, Yoshitomo Hayama, Yuichi Mitsui, Natsuki Sakurai, Hana Sarashina-Kida, Masayuki Nishide, Yohei Maeda, Hyota Takamatsu, Daisuke Okuzaki, Masaki Yamada, Masato Okada, Atsushi Kumanogoh
Macrophages play crucial roles in host defence and tissue homoeostasis, processes in which both environmental stimuli and intracellularly generated metabolites influence activation of macrophages. Activated macrophages are classified into M1 and M2 macrophages. It remains unclear how intracellular nutrition sufficiency, especially for amino acid, influences on macrophage activation. Here we show that a lysosomal adaptor protein Lamtor1, which forms an amino-acid sensing complex with lysosomal vacuolar-type H(+)-ATPase (v-ATPase), and is the scaffold for amino acid-activated mTORC1 (mechanistic target of rapamycin complex 1), is critically required for M2 polarization...
October 12, 2016: Nature Communications
(no author information available yet)
No abstract text is available yet for this article.
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Semjon Seemann, Amelie Lupp
BACKGROUND: Chemokine receptor 4 (CXCR4) is a multifunctional G protein-coupled receptor that is activated by its natural ligand, C-X-C motif chemokine 12 (CXCL12). As a likely member of the lipopolysaccharide (LPS)-sensing complex, CXCR4 is involved in pro-inflammatory cytokine production and exhibits substantial chemo-attractive activity for various inflammatory cells. Here, we aimed to characterize the effects of CXCR4 blockade in systemic inflammation and to evaluate its impact on organ function...
October 3, 2016: Journal of Biomedical Science
Lai Peng, Stephanie Piekos, Grace L Guo, Xiao-Bo Zhong
The expression of phase-I drug metabolizing enzymes in liver changes dramatically during postnatal liver maturation. Farnesoid X receptor (FXR) is critical for bile acid and lipid homeostasis in liver. However, the role of FXR in regulating ontogeny of phase-I drug metabolizing genes is not clear. Hence, we applied RNA-sequencing to quantify the developmental expression of phase-I genes in both Fxr-null and control (C57BL/6) mouse livers during development. Liver samples of male C57BL/6 and Fxr-null mice at 6 different ages from prenatal to adult were used...
September 2016: Acta Pharmaceutica Sinica. B
William D Hedrich, Hazem E Hassan, Hongbing Wang
Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously believed. The discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has sparked increasing interest in the genetic and xenobiotic factors contributing to the expression and function of the enzyme. The expression of CYP2B6 is regulated primarily by the xenobiotic receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) in the liver. In addition to CYP2B6, these receptors also mediate the inductive expression of CYP3A4, and a number of important phase II enzymes and drug transporters...
September 2016: Acta Pharmaceutica Sinica. B
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