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https://www.readbyqxmd.com/read/28545035/novel-ppar%C3%AE-agonist-mhy553-alleviates-hepatic-steatosis-by-increasing-fatty-acid-oxidation-and-decreasing-inflammation-during-aging
#1
Seong Min Kim, Bonggi Lee, Hye Jin An, Dae Hyun Kim, Kyung Chul Park, Sang-Gyun Noh, Ki Wung Chung, Eun Kyeong Lee, Kyung Mok Kim, Do Hyun Kim, Su Jeong Kim, Pusoon Chun, Ho Jeong Lee, Hyung Ryong Moon, Hae Young Chung
Hepatic steatosis is frequently observed in obese and aged individuals. Because hepatic steatosis is closely associated with metabolic syndromes, including insulin resistance, dyslipidemia, and inflammation, numerous efforts have been made to develop compounds that ameliorate it. Here, a novel peroxisome proliferator-activated receptor (PPAR) α agonist, 4-(benzo[d]thiazol-2-yl)benzene-1,3-diol (MHY553) was developed, and investigated its beneficial effects on hepatic steatosis using young and old Sprague-Dawley rats and HepG2 cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28544610/phenol-enriched-olive-oils-modify-paraoxonase-related-variables-a-randomized-crossover-controlled-trial
#2
Sara Fernández-Castillejo, Ana-Isabel García-Heredia, Rosa Solà, Jordi Camps, Maria-Carmen López de la Hazas, Marta Farràs, Anna Pedret, Úrsula Catalan, Laura Rubió, Maria-José Motilva, Olga Castañer, María-Isabel Covas, Rosa-Maria Valls
SCOPE: Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic of cardiovascular disease. Our aim was to assess short and long-term effects of virgin olive oils (VOO), enriched with their own phenolic compounds (PC; FVOO) or with them plus complementary PC from thyme (FVOOT), on PON-related variables and the mechanisms involved. METHODS AND RESULTS: Two randomized, controlled, double-blind, and crossover interventions were conducted...
May 25, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28543935/neurodegeneration-in-ataxia-telangiectasia-multiple-roles-of-atm-kinase-in-cellular-homeostasis
#3
REVIEW
Kay Rui Choy, Dianne J Watters
Ataxia-Telangiectasia (A-T) is characterized by neuronal degeneration, cancer, diabetes, immune deficiency and increased sensitivity to ionizing radiation. A-T is attributed to the deficiency of the protein kinase coded by the ATM (Ataxia-Telangiectasia Mutated) gene. ATM is a sensor of DNA Double Strand Breaks and signals to cell cycle checkpoints and the DNA repair machinery. ATM phosphorylates numerous substrates and activates many cell-signalling pathways. There has been considerable debate about whether a defective DNA damage response is causative of the neurological aspects of the disease...
May 22, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28543443/structural-review-of-ppar%C3%AE-in-complex-with-ligands-cartesian-and-dihedral-angle-principal-component-analyses-of-x-ray-crystallographic-data
#4
Åsmund Kaupang, Tuomo Laitinen, Antti Poso, Trond Vidar Hansen
Two decades of research into the ligand-dependent modulation of the activity of the peroxisome proliferator-activated receptor γ (PPARγ) have demonstrated the heterogeneous modes of action of PPARγ ligands, in terms of their interaction surfaces in the ligand-binding pocket, binding stoichiometry and ability to interact with functionally important parts of the receptor, through both direct and allosteric mechanisms. These findings signal the complex mechanistic bases of the distinct biological effects of different classes of PPARγ ligands...
May 24, 2017: Proteins
https://www.readbyqxmd.com/read/28542224/is-spaceflight-induced-immune-dysfunction-linked-to-systemic-changes-in-metabolism
#5
Michael J Pecaut, Xiao Wen Mao, Denise L Bellinger, Karen R Jonscher, Louis S Stodieck, Virginia L Ferguson, Ted A Bateman, Robert P Mohney, Daila S Gridley
The Space Shuttle Atlantis launched on its final mission (STS-135) on July 8, 2011. After just under 13 days, the shuttle landed safely at Kennedy Space Center (KSC) for the last time. Female C57BL/6J mice flew as part of the Commercial Biomedical Testing Module-3 (CBTM-3) payload. Ground controls were maintained at the KSC facility. Subsets of these mice were made available to investigators as part of NASA's Bio-specimen Sharing Program (BSP). Our group characterized cell phenotype distributions and phagocytic function in the spleen, catecholamine and corticosterone levels in the adrenal glands, and transcriptomics/metabolomics in the liver...
2017: PloS One
https://www.readbyqxmd.com/read/28542026/combination-drug-therapy-of-pioglitazone-and-d-cycloserine-attenuates-chronic-orofacial-neuropathic-pain-and-anxiety-by-improving-mitochondrial-function-following-trigeminal-nerve-injury
#6
Danielle N Lyons, Liping Zhang, Jignesh D Pandya, Robert J Danaher, Fei Ma, Craig S Miller, Patrick G Sullivan, Cristian Sirbu, Karin N Westlund
OBJECTIVES: The study aim was to determine how peripheral trigeminal nerve injury affects mitochondrial respiration and to test efficacy of combined treatment with two FDA approved drugs with potential for improving mitochondrial bioenergetics, pain and anxiety related behaviors in a chronic orofacial neuropathic pain mouse model. METHODS: Efficacy of (R)-(+)-4-amino-3-isoxazolidinone (D-cycloserine, DCS), an NMDA antagonist/agonist, and Pioglitazone (PIO), a selective agonist of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) was investigate in the trigeminal inflammatory compression (TIC) neuropathic nerve injury mouse model...
May 24, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28541534/effect-of-maternal-obesity-on-placental-lipid-metabolism
#7
Virtu Calabuig-Navarro, Maricela Haghiac, Judi Minium, Patricia Glazebrook, Geraldine Cheyana Ranasinghe, Charles Hoppel, Sylvie Hauguel de-Mouzon, Patrick Catalano, Perrie O'Tierney-Ginn
Obese women, on average, give birth to babies with high fat mass. Placental lipid metabolism alters fetal lipid delivery, potentially moderating neonatal adiposity, yet how it is affected by maternal obesity is poorly understood. We hypothesized that fatty acid (FA) accumulation (esterification) is higher, and FA oxidation (FAO) is lower, in placentas from obese, compared to lean women. We assessed acylcarnitine profiles (lipid oxidation intermediates) in mother-baby-placenta triads, in addition to lipid content, and mRNA/protein expression of key regulators of FA metabolism pathways, in placentas of lean and obese women with normal glucose tolerance recruited at scheduled term Cesarean delivery...
May 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28540526/high-fat-diet-inhibits-pgc-1%C3%AE-suppressive-effect-on-nf%C3%AE%C2%BAb-signaling-in-hepatocytes
#8
Wermerson Assunção Barroso, Vanessa Jacob Victorino, Isabela Casagrande Jeremias, Ricardo Costa Petroni, Suely Kunimi Kubo Ariga, Thiago A Salles, Denise Frediani Barbeiro, Thais Martins de Lima, Heraldo Possolo de Souza
PURPOSE: The peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) regulates the expression of genes implicated in fatty acid oxidation and oxidative phosphorylation. Its role in liver steatosis is well established, since mice with liver-specific deletion of PGC-1α exhibit lipid accumulation and high-fat diet reduces hepatic PGC-1α expression in mice. In this study, we investigated the role of PGC-1α in the inflammatory changes observed in steatohepatitis induced by high-fat diet...
May 24, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28539839/ppard-is-an-inhibitor-of-cartilage-growth-in-external-ears
#9
Zhen Zhang, Yanyu Duan, Zhongping Wu, Hui Zhang, Jun Ren, Lusheng Huang
Peroxisome proliferator-activated receptor beta/delta (PPARD) is an important determinant of multiple biological processes. Our previous studies identified a missense mutation in the PPARD gene that significantly reduces its transcription activity, and consequently causes enlarged external ears in pigs. However, the mechanisms underlying the causality has remained largely unknown. Here, we show that PPARD retards the development of auricular cartilage by accelerating the apoptosis of cartilage stem/progenitor cells (CSPCs), the terminal differentiation of cartilage cells and the degradation of cartilage extracellular matrix in the auricle...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28539716/prevention-mechanism-of-2-3-5-4-tetrahydroxy-stilbene-2-o-%C3%AE-d-glucoside-on-lipid-accumulation-in-steatosis-hepatic-l-02-cell
#10
Pei Lin, Jian-Mei Lu, Yan-Fang Wang, Wen Gu, Rong-Hua Zhao, Jie Yu
AIM: 2,3,5,4'-Tetrahydroxy-stilbene-2-O-β-d-glucoside (TSG), a natural stilbene, shows great activities in hepatic lipid regulation, especially for hepatic triglyceride lowering. However, information about its mechanisms on biosynthesis and degradation of triglyceride is still limited. This research pays close attention to clarify the mechanism of TSG on prevention of hepatic lipid accumulation. MATERIALS AND METHODS: TSG was given to steatosis hepatocyte L-02 cell induced by fat emulsion incubation...
April 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28539218/switching-subtype-selectivity-fragment-replacement-strategy-affords-novel-class-of-peroxisome-proliferator-activated-receptor-%C3%AE-%C3%AE-ppar%C3%AE-%C3%AE-dual-agonists
#11
Ryuta Shioi, Shogo Okazaki, Tomomi Noguchi-Yachide, Minoru Ishikawa, Makoto Makishima, Yuichi Hashimoto, Takao Yamaguchi
Peroxisome proliferator-activated receptors (PPARs) are important drug targets for treatment of dyslipidemia, type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and great efforts have been made to develop novel PPAR ligands. However, most existing PPAR ligands contain a carboxylic acid (CA) or thiazolidinedione (TZD) structure (acidic head group) that is essential for activity. We recently discovered non-CA/TZD class PPARα/δ partial agonists, which contain an acetamide moiety and adjacent methyl group, linked to a 1,2,4-oxadiazole ring ("fragment a")...
May 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28539091/in-silico-identification-of-potential-drug-compound-against-peroxisome-proliferator-activated-receptor-gamma-by-virtual-screening-and-toxicity-studies-for-treatment-of-diabetic-nephropathy
#12
Smrita Singh, Aparajita Mohanty
Diabetic Nephropathy is a serious complication of Diabetes Mellitus. Current therapeutic strategies of Diabetic Nephropathy are based on control of modifiable risks like hypertension, glucose levels, and dyslipidemia. Peroxisome proliferator activated receptor-gamma (PPAR-γ) is implicated in several metabolic syndromes including Diabetic Nephropathy, besides obesity, insulin insensitivity, dislipidemia, inflammation and hypertension. In the present study, virtual screening of 617 compounds from two different public databases was done against PPAR- γ with an objective to find a possible lead compound...
May 24, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28538724/applying-systems-level-spectral-imaging-and-analysis-to-reveal-the-organelle-interactome
#13
Alex M Valm, Sarah Cohen, Wesley R Legant, Justin Melunis, Uri Hershberg, Eric Wait, Andrew R Cohen, Michael W Davidson, Eric Betzig, Jennifer Lippincott-Schwartz
The organization of the eukaryotic cell into discrete membrane-bound organelles allows for the separation of incompatible biochemical processes, but the activities of these organelles must be coordinated. For example, lipid metabolism is distributed between the endoplasmic reticulum for lipid synthesis, lipid droplets for storage and transport, mitochondria and peroxisomes for β-oxidation, and lysosomes for lipid hydrolysis and recycling. It is increasingly recognized that organelle contacts have a vital role in diverse cellular functions...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538669/the-peroxisome-mitochondria-connection-how-and-why
#14
REVIEW
Marc Fransen, Celien Lismont, Paul Walton
Over the past decades, peroxisomes have emerged as key regulators in overall cellular lipid and reactive oxygen species metabolism. In mammals, these organelles have also been recognized as important hubs in redox-, lipid-, inflammatory-, and innate immune-signaling networks. To exert these activities, peroxisomes must interact both functionally and physically with other cell organelles. This review provides a comprehensive look of what is currently known about the interconnectivity between peroxisomes and mitochondria within mammalian cells...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28537652/efficacy-and-safety-of-very-low-calorie-ketogenic-diet-a-double-blind-randomized-crossover-study
#15
C Colica, G Merra, A Gasbarrini, A De Lorenzo, G Cioccoloni, P Gualtieri, M A Perrone, S Bernardini, V Bernardo, L Di Renzo, M Marchetti
OBJECTIVE: To verify safety respect to weight loss, cardiometabolic diseases of short-term Very low-calorie ketogenic diets (VLCKDs, <800 kcal day-1). PATIENTS AND METHODS: Randomized cross-over trial with placebo. The study had no. 2 dietary treatment (DT), conducted in two arms: (1) VLCKD1 in which 50% of protein intake is replaced with synthetic amino acids; (2) VLCKD2 with placebo. The VLCKDs (<800 kcal day-1) were different in term of protein content and quality each arm lasted three weeks (wks)...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28536637/ppar%C3%AE-agonist-through-the-terminal-differentiation-phase-is-essential-for-adipogenic-differentiation-of-fetal-ovine-preadipocytes
#16
Yong Pu, Almudena Veiga-Lopez
BACKGROUND: Although the 3T3-L1 preadipocyte cell line represents an informative model for in vitro adipogenesis research, primary cultured cells are often needed to understand particular human or animal metabolic phenotypes. As demonstrated by in vitro cultured preadipocytes from large mammalian species, primary cultured cells require specific adipogenic differentiation conditions different to that of the 3T3-L1 cell line. These conditions are also species-specific and require optimization steps...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28536504/thyroid-hormone-induces-pgc-1%C3%AE-during-dendritic-outgrowth-in-mouse-cerebellar-purkinje-cells
#17
Tetsu Hatsukano, Junko Kurisu, Kansai Fukumitsu, Kazuto Fujishima, Mineko Kengaku
Thyroid hormone 3,3',5-Triiodo-L-thyronine (T3) is essential for proper brain development. Perinatal loss of T3 causes severe growth defects in neurons and glia, including strong inhibition of dendrite formation in Purkinje cells in the cerebellar cortex. Here we show that T3 promotes dendritic outgrowth of Purkinje cells through induction of peroxisome proliferator-activated receptor gamma (PPARγ) co-activator 1α (PGC-1α), a master regulator of mitochondrial biogenesis. PGC-1α expression in Purkinje cells is upregulated during dendritic outgrowth in normal mice, while it is significantly retarded in hypothyroid mice or in cultures depleted of T3...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28536293/peroxisome-proliferator-activated-receptor-%C3%AE-agonism-attenuates-endotoxaemia-induced-muscle-protein-loss-and-lactate-accumulation-in%C3%A2-rats
#18
Hannah Crossland, Dumitru Constantin-Teodosiu, Sheila Gardiner, Paul Greenhaff
The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi) appears to provide protection against organ dysfunction during endotoxaemia. We examined the potential benefits of Rosi on skeletal muscle protein maintenance and carbohydrate metabolism during lipopolysaccharide (LPS)-induced endotoxaemia. Sprague-Dawley rats were fed either standard chow (control) or standard chow containing Rosi (8.5±0.1 mg(.)kg(-1.)day(-1)) for two weeks before and during 24 h continuous intravenous infusion of LPS (15 μg(...
May 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28535809/safety-and-tolerability-of-adjunctive-rosiglitazone-treatment-for-children-with-uncomplicated-malaria
#19
Rosauro Varo, Valerie M Crowley, Antonio Sitoe, Lola Madrid, Lena Serghides, Rubao Bila, Helio Mucavele, Alfredo Mayor, Quique Bassat, Kevin C Kain
BACKGROUND: Despite the widespread use and availability of rapidly acting anti-malarials, the fatality rate of severe malaria in sub-Saharan Africa remains high. Adjunctive therapies that target the host response to malaria infection may further decrease mortality over that of anti-malarial agents alone. Peroxisome proliferator-activated receptor-gamma agonists (e.g. rosiglitazone) have been shown to act on several pathways implicated in the pathogenesis of severe malaria and may improve clinical outcome as an adjunctive intervention...
May 23, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28535598/antarctic-seals-molecular-biomarkers-as-indicators-for-pollutant-exposure-health-effects-and-diet
#20
K Lehnert, L Weirup, K C Harding, T Härkönen, O Karlsson, J Teilmann
Weddell (Leptonychotes weddellii), Ross (Ommatophoca rossii) and crabeater seals (Lobodon carcinophaga) are phocid seals with a circumpolar distribution around Antarctica. As long-lived and large top predators, they bioaccumulate contaminants and are considered as sentinels of ecosystem health. Antarctic seals are increasingly exposed to climate change, pollution, shipping and fisheries. To reveal and understand possible anthropogenic impacts on their immune and health status, this study investigates sensitive biomarkers of the xenobiotic metabolism and immune system in relation to mercury (Hg) burden...
May 19, 2017: Science of the Total Environment
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