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https://www.readbyqxmd.com/read/27914812/protective-effects-of-gomisin-n-against-hepatic-steatosis-through-ampk-activation
#1
Ye-Rang Yun, Ji-Hyun Kim, Ji Ha Kim, Myeong Ho Jung
Gomisin N (GN) is a phytochemical derived from Schisandra chinensis. It has been reported to exert a protective effect against hepatic steatosis by attenuating endoplasmic recticulum (ER) stress. However, the detailed mechanism by which GN inhibits hepatic steatosis remains to be elucidated. In this study, we examined whether GN activates AMP-activated protein kinase (AMPK) and exerts therapeutic effects on liver X receptor (LXR)- or palmitic acid (PA)-induced triglyceride (TG) accumulation in HepG2 cells. Furthermore, in vivo protective effects of GN against hepatic steatosis were assessed in high-fat diet (HFD)-induced obese mice...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27890613/activation-of-ppar%C3%AE-does-not-contribute-to-macrophage-abca1-expression-and-abca1-mediated-cholesterol-efflux-to-apoai
#2
Meixiu Jiang, Xiaoju Li
Activation of macrophage ABCA1/G1 expression and cholesterol efflux is believed one of the mechanisms by which PPARγ inhibits atherosclerosis. PPARγ can also activate CD36 expression, a receptor for oxLDL, which may supply LXR ligands to activate LXR-ABCA1/G1 pathways. However, the controversial effects of PPARγ on ABCA1 expression have been reported. In this study, we used peritoneal macrophages isolated from wild type and CD36 deficient (CD36(-/-)) mice to clarify if PPARγ ligands can influence ABCA1 expression by CD36 function...
November 24, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27888103/luteolin-improves-non-alcoholic-fatty-liver-disease-in-db-db-mice-by-inhibition-of-liver-x-receptor-activation-to-down-regulate-expression-of-sterol-regulatory-element-binding-protein-1c
#3
Ye Yin, Lu Gao, Haiyan Lin, Yue Wu, Xiao Han, Yunxia Zhu, Jie Li
In this study, we report that daily administration of luteolin for 8 weeks improved hepatic steatosis by repressing hepatic TG accumulation and increasing glycogen storage. Luteolin inhibited hepatic de novo lipid synthesis by regulating the LXR-SREBP-1c signaling pathway, which is over-activated in the livers of db/db mice. Further in vitro studies revealed that luteolin can competitively bind to the ligand binding domain to suppress the LXR activation induced by an LXR agonist and high glucose, thereby decreasing TG accumulation in HepG2 cells and primary hepatocytes...
November 22, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27877090/genetic-variant-in-flavin-containing-monooxygenase-3-alters-lipid-metabolism-in-laying-hens-in-a-diet-specific-manner
#4
Jing Wang, Cheng Long, Haijun Zhang, Yanan Zhang, Hao Wang, Hongyuan Yue, Xiaocui Wang, Shugeng Wu, Guanghai Qi
Genetic variant T329S in flavin-containing monooxygenase 3 (FMO3) impairs trimethylamine (TMA) metabolism in birds. The TMA metabolism that under complex genetic and dietary regulation, closely linked to cardiovascular disease risk. We determined whether the genetic defects in TMA metabolism may change other metabolic traits in birds, determined whether the genetic effects depend on diets, and to identify genes or gene pathways that underlie the metabolic alteration induced by genetic and diet factors. We used hens genotyped as FMO3 c...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27867498/bone-muscle-crosstalk-targets-muscle-regeneration-pathway-regulated-by-core-circadian-transcriptional-repressors-dec1-and-dec2
#5
REVIEW
Jeffrey P Gorski, Jeffrey L Price
Deletion of proprotein convertase Mbtps1 in bone osteocytes leads to a significant postnatal increase in skeletal muscle size and contractile function, while causing only a 25% increase in stiffness in long bones. Concerns about leakiness in skeletal muscle were discounted since Cre recombinase expression does not account for our findings, and, Mbtps1 protein and mRNA is not deleted. Interestingly, the response of normal skeletal muscle to exercise and the regenerative response of skeletal muscle to the deletion of Mbtps1 in bone share some key regulatory features including a preference for slow twitch muscle fibers...
2016: BoneKEy Reports
https://www.readbyqxmd.com/read/27859514/preserving-lxr-by-inhibiting-t39-a-step-closer-to-treating-atherosclerosis-and-steatohepatitis
#6
Melanie Tran, Li Wang
No abstract text is available yet for this article.
November 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27846372/loss-of-ulk1-increases-rps6kb1-ncor1-repression-of-nr1h-lxr-mediated-scd1-transcription-and-augments-lipotoxicity-in-hepatic-cells
#7
Rohit Anthony Sinha, Brijesh K Singh, Jin Zhou, Sherwin Xie, Benjamin L Farah, Ronny Lesmana, Kenji Ohba, Madhulika Tripathi, Sujoy Ghosh, Anthony N Hollenberg, Paul M Yen
Lipotoxicity caused by saturated fatty acids (SFAs) induces tissue damage and inflammation in metabolic disorders. SCD1 (stearoyl-Coenzyme A desaturase 1) converts SFAs to mono-unsaturated fatty acids (MUFAs) that are incorporated into triglycerides and stored in lipid droplets. SCD1 thus helps protect hepatocytes from lipotoxicity and its reduced expression is associated with increased lipotoxic injury in cultured hepatic cells and mouse models. To further understand the role of SCD1 in lipotoxicity, we examined the regulation of Scd1 in hepatic cells treated with palmitate, and found that NR1H/LXR (nuclear receptor subfamily 1 group H) ligand, GW3965, induced Scd1 expression and lipid droplet formation to improve cell survival...
November 15, 2016: Autophagy
https://www.readbyqxmd.com/read/27832992/studies-on-the-regulation-of-lipid-metabolism-and-its-mechanism-of-the-iridoids-rich-fraction-in-valeriana-jatamansi-jones
#8
Jiali Zhu, Keke Xu, Xuemei Zhang, Jiahong Cao, Zhanrong Jia, Ruocong Yang, Chaoying Ma, Chang Chen, Tiane Zhang, Zhiyong Yan
Valeriana jatamansi Jones, a plant with heart-shaped leaves in the Valeriana genus of Valerianaceae, is widely used in Chinese folk medicine. Iridoid is an important constituent of V. jatamansi that contributes to the pharmacological efficacy of the herb. This study aims to investigate the regulation of lipid metabolism and its mechanism of the iridoids rich fraction in V. jatamansi (IRFV). A high fat diet was used to establish the hyperlipidemia rat model, with 2mg/kg/d of simvastatin as a positive control, fed with 7...
November 7, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27832630/decreased-mir-155-level-in-the-peripheral-blood-of-non-alcoholic-fatty-liver-disease-patients-may-serve-as-a-biomarker-and-may-influence-lxr-activity
#9
Lei Wang, Ning Zhang, Zun Wang, Dong-Mei Ai, Zhen-Yu Cao, Hua-Ping Pan
BACKGROUND: Obesity is now a common risk factor for non-alcoholic fatty liver disease (NAFLD). Thus, it is important to explore its underlying mechanisms. METHODS: Total RNA was extracted from peripheral whole blood samples from 50 NAFLD patients and 50 healthy controls. In addition, human liver specimens were obtained through liver biopsies from NAFLD patients and healthy controls. The level of miRNA was studied using real-time PCR. The expression of lipogenic genes was analyzed using western blot, and a dual luciferase reporter assay was conducted to identify the possible target gene...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27829662/high-glucose-upregulates-bace1-mediated-a%C3%AE-production-through-ros-dependent-hif-1%C3%AE-and-lxr%C3%AE-abca1-regulated-lipid-raft-reorganization-in-sk-n-mc-cells
#10
Hyun Jik Lee, Jung Min Ryu, Young Hyun Jung, Sei-Jung Lee, Jeong Yeon Kim, Sang Hun Lee, In Koo Hwang, Je Kyung Seong, Ho Jae Han
There is an accumulation of evidence indicating that the risk of Alzheimer's disease is associated with diabetes mellitus, an indicator of high glucose concentrations in blood plasma. This study investigated the effect of high glucose on BACE1 expression and amyloidogenesis in vivo, and we present details of the mechanism associated with those effects. Our results, using ZLC and ZDF rat models, showed that ZDF rats have high levels of amyloid-beta (Aβ), phosphorylated tau, BACE1, and APP-C99. In vitro result with mouse hippocampal neuron and SK-N-MC, high glucose stimulated Aβ secretion and apoptosis in a dose-dependent manner...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27806127/rifampicin-induced-hepatic-lipid-accumulation-association-with-up-regulation-of-peroxisome-proliferator-activated-receptor-%C3%AE-in-mouse-liver
#11
Jia-Hui Huang, Cheng Zhang, Da-Gang Zhang, Lu Li, Xi Chen, De-Xiang Xu
Previous study found that rifampicin caused intrahepatic cholestasis. This study investigated the effects of rifampicin on hepatic lipid metabolism. Mice were orally administered with rifampicin (200 mg/kg) daily for different periods. Results showed that serum TG level was progressively reduced after a short elevation. By contrast, hepatic TG content was markedly increased in rifampicin-treated mice. An obvious hepatic lipid accumulation, as determined by Oil Red O staining, was observed in mice treated with rifampicin for more than one week...
2016: PloS One
https://www.readbyqxmd.com/read/27793810/glioblastomas-exhibit-a-targetable-dependency-on-exogenous-cholesterol
#12
(no author information available yet)
GBMs depend on exogenous cholesterol released from normal brain parenchyma via LXR-mediated efflux.
December 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27788593/paraquat-induces-peripheral-myelin-disruption-and-locomotor-defects-crosstalk-with-lxr-and-wnt-pathways
#13
Mehdi Hichor, Nirmal Kumar Sampathkumar, Julia Montanaro, Didier Borderie, Patrice X Petit, Victor Gorgievski, Eleni T Tzavara, Assaad Antoine Eid, Frederic Charbonnier, Julien Grenier, Charbel Massaad
AIMS: Paraquat (PQT), a redox-active herbicide, is a free radical producing molecule, causing damages particularly to the nervous system thus employed as an animal model for Parkinson's disease. However, its impact on peripheral nerve demyelination is still unknown. Our aim is to decipher the influence of PQT-induced ROS production on peripheral myelin. RESULTS: We report that PQT provokes severe locomotor and sensory defects in mice. PQT elicited an oxidative stress in the nerve, resulting in an increase of lipid peroxidation and protein carbonylation despite the induction of Nrf2-dependant antioxidant defenses...
October 27, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27787652/transcriptional-control-of-apoptotic-cell-clearance-by-macrophage-nuclear-receptors
#14
Tamás Röszer
Apoptotic cell clearance by macrophages is key for normal tissue development and homeostasis. Nuclear receptors, such as peroxisome proliferator activated receptors (PPARs), liver X receptor (LXR), retinoic acid receptor (RAR), retinoid X receptor (RXR) and glucocorticoid receptor (GR) orchestrate this vital process. The underlying mechanism involves the transcriptional control of key genes of apoptotic cell recognition and internalization, such as Cd36, Mertk, Axl, C1qa, Tgm2, Abca1. In addition, apoptotic cell uptake leads to M2 activation of macrophages, and this process is also controlled at the gene transcription level by nuclear receptors...
October 27, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27779191/25-hydroxycholesterol-contributes-to-cerebral-inflammation-of-x-linked-adrenoleukodystrophy-through-activation-of-the-nlrp3-inflammasome
#15
Jiho Jang, Sangjun Park, Hye Jin Hur, Hyun-Ju Cho, Inhwa Hwang, Yun Pyo Kang, Isak Im, Hyunji Lee, Eunju Lee, Wonsuk Yang, Hoon-Chul Kang, Sung Won Kwon, Je-Wook Yu, Dong-Wook Kim
X-linked adrenoleukodystrophy (X-ALD), caused by an ABCD1 mutation, is a progressive neurodegenerative disorder associated with the accumulation of very long-chain fatty acids (VLCFA). Cerebral inflammatory demyelination is the major feature of childhood cerebral ALD (CCALD), the most severe form of ALD, but its underlying mechanism remains poorly understood. Here, we identify the aberrant production of cholesterol 25-hydroxylase (CH25H) and 25-hydroxycholesterol (25-HC) in the cellular context of CCALD based on the analysis of ALD patient-derived induced pluripotent stem cells and ex vivo fibroblasts...
October 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27777632/the-effect-of-maternal-undernutrition-on-the-rat-placental-transcriptome-protein-restriction-up-regulates-cholesterol-transport
#16
Zoe Daniel, Angelina Swali, Richard Emes, Simon C Langley-Evans
BACKGROUND: Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences. METHODS: Pregnant rats were fed control or a low protein diet from conception to day 13 gestation...
2016: Genes & Nutrition
https://www.readbyqxmd.com/read/27763549/maternal-betaine-supplementation-throughout-gestation-and-lactation-modifies-hepatic-cholesterol-metabolic-genes-in-weaning-piglets-via-ampk-lxr-mediated-pathway-and-histone-modification
#17
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
https://www.readbyqxmd.com/read/27751910/transcriptome-profiling-of-equine-vitamin-e-deficient-neuroaxonal-dystrophy-identifies-upregulation-of-liver-x-receptor-target-genes
#18
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 15, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27746237/the-role-of-microrna-155-liver-x-receptor-pathway-in-experimental-and-idiopathic-pulmonary-fibrosis
#19
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: We sought to determine the regulatory role of microRNA (miR)-155 in the profibrotic function of murine lung macrophages and fibroblasts, IPF lung fibroblasts, and its contribution to experimental pulmonary fibrosis...
October 14, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27746144/an-lxr-cholesterol-axis-creates-a-metabolic-co-dependency-for-brain-cancers
#20
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...
November 14, 2016: Cancer Cell
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