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https://www.readbyqxmd.com/read/28398573/skeletal-muscle-pgc1%C3%AE-1-nucleosome-position-and-260nt-dna-methylation-determine-exercise-response-and-prevent-ectopic-lipid-accumulation-in-men
#1
Sudip Bajpeyi, Jeffrey D Covington, Erin M Taylor, Laura K Stewart, Jose E Galgani, Tara M Henagan
Endurance exercise has been shown to improve lipid oxidation and increase mitochondrial content in skeletal muscle: two features that have shown dependence on increased expression of the PPAR gamma co-activator 1 alpha (PGC1α). It is also hypothesized that exercise related alterations in PGC1α expression occur through epigenetic regulation of nucleosome positioning in association with differential DNA methylation status within the PCG1α promoter. Here we show that when primary human myotubes from obese, type 2 diabetics are exposed to lipolytic stimulus (PFI) in vitro, nucleosome occupancy surrounding the -260 nucleotide (nt) region, a known regulatory DNA methylation site, is reduced...
April 10, 2017: Endocrinology
https://www.readbyqxmd.com/read/28391584/the-effect-of-ppar%C3%AE-agonist-on-sglt2-and-glucagon-expressions-in-alpha-cells-under-hyperglycemia
#2
M Kim, E J Lee, H M Shin, H S Jung, T K Kim, T N Kim, M J Kwon, S H Lee, B D Rhee, J H Park
BACKGROUND: Although sodium glucose cotransporter 2 (SGLT2) inhibitors have many beneficial effects for type 2 diabetes, including decreased cardiovascular death, recent reports that they increased glucagon through SGLT2 inhibition raised some concern. Troglitazone, Peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, was reported to increase SGLT2 in renal proximal tubule cells, but its role on pancreatic alpha cells have not been reported. We investigated the effect of troglitazone on SGLT2 expression in alpha cells and subsequent glucagon regulation in hyperglycemia...
April 8, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28386478/changes-in-the-microrna-profile-observed-in-the-subcutaneous-adipose-tissue-of-obese-patients-after-laparoscopic-adjustable-gastric-banding
#3
Carmela Nardelli, Laura Iaffaldano, Vincenzo Pilone, Giuseppe Labruna, Maddalena Ferrigno, Nicola Carlomagno, Concetta Anna Dodaro, Pietro Forestieri, Pasqualina Buono, Francesco Salvatore, Lucia Sacchetti
Background. Laparoscopic adjustable gastric banding (LAGB) results in significant lasting weight loss and improved metabolism in obese patients. To evaluate whether epigenetic factors could concur to these benefits, we investigated the subcutaneous adipose tissue (SAT) microRNA (miRNA) profile before (T0) and three years (T1) after LAGB in three morbidly obese women. Case Reports. SAT miRNA profiling, evaluated by TaqMan Array, showed four downexpressed (miR-519d, miR-299-5p, miR-212, and miR-671-3p) and two upexpressed (miR-370 and miR-487a) miRNAs at T1 versus T0...
2017: Journal of Obesity
https://www.readbyqxmd.com/read/28369613/collaborative-cross-mouse-population-enables-refinements-to-characterization-of-the-variability-in-toxicokinetics-of-trichloroethylene-and-provides-genetic-evidence-for-the-role-of-ppar-pathway-in-its-oxidative-metabolism
#4
Abhishek Venkatratnam, Shinji Furuya, Oksana Kosyk, Avram Gold, Wanda Bodnar, Kranti Konganti, David W Threadgill, Kevin M Gillespie, David L Aylor, Fred A Wright, Weihsueh A Chiu, Ivan Rusyn
Background: Trichloroethylene (TCE) is a known carcinogen in humans and rodents. Previous studies of inter-strain variability in TCE metabolism were conducted in multi-strain panels of classical inbred mice with limited genetic diversity to identify gene-environment interactions associated with chemical exposure. Objectives: To evaluate inter-strain variability in TCE metabolism and identify genetic determinants that are associated with TCE metabolism and effects using Collaborative Cross (CC), a large panel of genetically diverse strains of mice...
March 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28343425/ppar-%C3%AE-agonists-are-still-on-the-rise-an-update-on-clinical-and-experimental-findings
#5
Nicola Ferri, Alberto Corsini, Cesare Sirtori, Massimiliano Ruscica
Non-fasting plasma triglyceride (TG) and remnant cholesterol levels, cholesterol content of triglyceride-rich lipoproteins, have been suggested to be an additional cause of cardiovascular diseases; thus, pharmacological TG-lowering with fibrates, activators of PPAR-alpha system, has been linked to risk reduction. Areas covered: This manuscript reviews available evidence on clinical trials involving highly selective PPAR-α agonists (i.e., pemafibrate) and drugs used in the pre-clinical and experimental setting (e...
May 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28337143/anti-adipogenic-effects-and-mechanisms-of-ginsenoside-rg3-in-pre-adipocytes-and-obese-mice
#6
Longyun Zhang, Lijuan Zhang, Xiaoyong Wang, Hongwei Si
Red or black ginseng has been reported more powerful than white/fresh ginseng in dealing with various diseases/conditions including obesity. The major reason is that heating/steaming, the process of making red or black ginseng, produces large amount of bioactive compounds including ginsenoside Rg3 (Rg3), which are trace in fresh or white ginseng. In the present study, Rg3 was applied both in pre-adipocytes and obese mice to investigate the anti-adipogenic effects and relevant mechanisms. Our results show that Rg3 dose-dependently inhibited cell differentiation both in 3T3-L1 cells (30, 50, and 100 μM) and human primary pre-adipocytes (10, 20, and 30 μM)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28320596/phillyrin-lowers-body-weight-in-obese-mice-via-the-modulation-of-ppar-beta-delta-angptl-4-pathway
#7
Hong-Bo Xiao, Guo-Guang Sui, Xiang-Yang Lu
OBJECTIVE: Previous investigations have shown that the peroxisome proliferator activated receptor beta/delta (PPAR<beta>/<delta>)-angiopoietin-like protein 4 (ANGPTL4) pathways may be a new pharmacologic target for treatment of obesity. The present study was conducted to test the effect of phillyrin, ‎a glucoside, on obesity in mice. METHOD: Fifty mice were randomly divided into 5 groups (n=10): control group (C57BL/6J mice), obese mice group, two groups of obese mice treated with phillyrin (15 or 45mg/kg/day), one group of obese mice treated with PPAR<beta>/<delta> agonist GW0742 (3mg/kg/day)...
March 17, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/28303105/caloric-restriction-is-more-efficient-than-physical-exercise-to-protect-from-cisplatin-nephrotoxicity-via-ppar-alpha-activation
#8
Gabriel R Estrela, Frederick Wasinski, Rogério O Batista, Meire I Hiyane, Raphael J F Felizardo, Flavia Cunha, Danilo C de Almeida, Denise M A C Malheiros, Niels O S Câmara, Carlos C Barros, Michael Bader, Ronaldo C Araujo
The antineoplastic drug cisplatin promotes renal injury, which limits its use. Protocols that reduce renal cisplatin toxicity will allow higher doses to be used in cisplatin treatment. Here, we compare physical exercise and caloric restriction (CR) as protocols to reduce cisplatin renal injury in mice. Male C57BL/6 were divided into four groups: Control, cisplatin, exercise + cisplatin, and 30% CR + cisplatin. Animals were injected with a single dose of cisplatin (20 mg/kg i.p.) and sacrificed 96 h after injection...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28274810/non-clinical-safety-evaluation-and-risk-assessment-to-human-of-aleglitazar-a-dual-ppar-%C3%AE-%C3%AE-agonist-and-its-major-human-metabolite
#9
Martin Bopst, Elke-Astrid Atzpodien
The non-clinical safety profile of aleglitazar, a peroxisome proliferator activated receptor alpha/gamma agonist, and its major human metabolite M6 was studied in a complete package consisting of drug metabolism and pharmacokinetics characterization, safety pharmacology, genotoxicity, repeat dose toxicity, reproductive toxicity and carcinogenicity studies. These studies identified the following main targets similar to other PPAR agonists: red blood cell parameters, liver, heart, kidney, ovaries, testes, bone marrow, adipose tissue, and fluid accumulation...
March 6, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28223870/bioactivity-and-chemical-characterization-of-acalypha-fruticosa-forssk-growing-in-saudi-arabia
#10
Ghada Ahmed Fawzy, Areej Mohammad Al-Taweel, Shagufta Perveen, Shabana Iqrar Khan, Fatma Abdulaziz Al-Omary
Acalypha is an important genus of the Euphorbiaceae family. The genus is represented by five species in Saudi Arabia. Acalypha fruticosa Forssk. Fl. Aeg is traditionally used as a cure for stomachache, dyspepsia, rheumatism, dermatitis, and swellings of the body. The present study endeavors to provide a phytochemical and biological evaluation of the plant, with the aim of relating activity to constituting secondary metabolites in the plant. Column chromatographic separation of the methanol extract led to the isolation of four compounds namely 2-methyl-5,7-dihydroxychromone 5-O-β-d-glucopyranoside 1, acalyphin 2, apigenin 3 and kaempferol 3-O-rutinoside 4...
January 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28219837/chronic-maternal-calcium-and-25-hydroxyvitamin-d-deficiency-in-wistar-rats-programs-abnormal-hepatic-gene-expression-leading-to-hepatic-steatosis-in-female-offspring
#11
Sona S Sharma, Nivedita M Jangale, Abhay M Harsulkar, Medha K Gokhale, Bimba N Joshi
Importance of calcium and vitamin D deficiency is well established in adult dyslipidemia. We hypothesized that maternal calcium and vitamin D deficiency could alter offspring's lipid metabolism. Our objective was to investigate the effect of maternal dietary calcium and vitamin D deficiency on lipid metabolism and liver function of the F1 generation offspring. intergenerational calcium-deficient (CaD) and vitamin D-deficient (VDD) models were developed by mating normal male rats with deficient females and continuing maternal-deficient diets through pregnancy and lactation...
February 8, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28177670/effect-of-vitamin-d-on-isoprenaline-induced-myocardial-infarction-in-rats-possible-role-of-peroxisome-proliferator-activated-receptor-%C3%A9-ppar-%C3%A9
#12
Ola Ahmed El-Gohary, Mona Maher Allam
Infarct-like lesion induced by isoprenaline is a well-known model to study myocardial infarction (MI). Vitamin D has been shown to have anti-inflammatory and antioxidant effects. Recent studies highlighted cross talk between vitamin D and peroxisome proliferator-activated receptor gamma (PPAR- ɣ). The present study was designed to investigate the effect of pretreatment with vitamin D on the isoprenaline-induced infarct-like lesion in rats and the role of PPAR- ɣ as a novel mechanism in vitamin D-mediated cardio protective effect...
January 22, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28144388/hepatic-structural-enhancement-and-insulin-resistance-amelioration-due-to-at1-receptor-blockade
#13
EDITORIAL
Vanessa Souza-Mello
Over the last decade, the role of renin-angiotensin system (RAS) on the development of obesity and its comorbidities has been extensively addressed. Both circulating and local RAS components are up-regulated in obesity and involved in non-alcoholic fatty liver disease onset. Pharmacological manipulations of RAS are viable strategies to tackle metabolic impairments caused by the excessive body fat mass. Renin inhibitors rescue insulin resistance, but do not have marked effects on hepatic steatosis. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARB) yield beneficial hepatic remodeling...
January 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28135036/a-molecular-dynamics-shared-pharmacophore-approach-to-boost-early-enrichment-virtual-screening-a-case-study-on-ppar-alpha
#14
Ugo Perricone, Marcus Wieder, Thomas Seidel, Thierry Langer, Alessandro Padova, Anna Maria Almerico, Marco Tutone
Molecular Dynamics (MD) simulations can be used, prior to virtual screening, to add flexibility to proteins, and study them in a dynamical way. Furthermore, the use of multiple crystal structures of the same protein containing different co-crystallised ligands, can help to better elucidate the role of the ligand on protein active conformation, and then explore the most common interactions between small molecules and the receptor. In this work, we evaluated the contribution of the combined use of MD on crystal structures containing the same protein but different ligands to examine the crucial ligand-protein interactions within the complexes...
January 30, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28131830/suppression-of-nrf2-attenuates-adipogenesis-and-decreases-fgf21-expression-through-ppar-gamma-in-3t3-l1-cells
#15
Bo-Rahm Kim, Gha Young Lee, Hyeree Yu, Hyo Jin Maeng, Tae Jung Oh, Kyoung Min Kim, Jae Hoon Moon, Soo Lim, Hak Chul Jang, Sung Hee Choi
Adipogenesis is the process of differentiation from preadipocytes to adipocytes and is orchestrated by various transcription factors, such as the peroxisome proliferator-activated receptor gamma (PPARγ) and the CCAAT-enhancer-binding protein alpha (C/EBPα). Oxidative stress is also a crucial factor in adipogenesis, and adipocyte differentiation is affected by the cellular redox status. The nuclear factor E2-related factor 2 (Nrf2), which is a basic leucine zipper (bZIP) transcription factor, acts as a regulator of cellular oxidative stress...
January 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28125276/molecular-factors-involved-in-the-hypolipidemic-and-insulin-sensitizing-effects-of-a-ginger-zingiber-officinale-roscoe-extract-in-rats-fed-a-high-fat-diet
#16
Natalia de Las Heras, María Valero-Muñoz, Beatriz Martín-Fernández, Sandra Ballesteros, Antonio López-Farré, Baltasar Ruiz-Roso, Vicente Lahera
Hypolipidemic and hypoglycemic properties of ginger in animal models have been reported. However, information related to the mechanisms and factors involved in the metabolic effects of ginger at a hepatic level are limited. The aim of the present study was to investigate molecular factors involved in the hypoglycemic and hypolipidemic effects of a hydroethanolic ginger extract (GE) in the liver of rats fed a high-fat diet (HFD). The study was conducted in male Wistar rats divided into the following 3 groups: (i) Rats fed a standard diet (3...
February 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28116391/a-rich-medium-chain-triacylglycerol-diet-benefits-adiposity-but-has-adverse-effects-on-the-markers-of-hepatic-lipogenesis-and-beta-oxidation
#17
Carolina Maria de Oliveira Chamma, Thereza Cristina Lonzetti Bargut, Carlos Alberto Mandarim-de-Lacerda, Marcia Barbosa Aguila
We investigated the increasing amounts of medium-chain triacylglycerol (MCT) in the diet on hepatic lipid metabolism. Mature C57BL/6 male mice were randomly divided into five groups (n = 10/group). The animals received their diet for 12 weeks, as a control (C group, 10% of energy from lipids); high-fat lard (HF group, isoenergetic diet, 50% of energy from lipids with lard); a mixture of lard and MCT oil (with a gradual replacement of lard by MCT: HF-MCT25%, HF-MCT75%, and HF-MCT100% groups). At euthanasia, we collected blood and dissected the liver for analyses (glucose, insulin, HOMA-IR, QUICK index, and triacylglycerol, light microscopy, western blotting, and RT-qPCR)...
February 22, 2017: Food & Function
https://www.readbyqxmd.com/read/28109294/probing-the-intermolecular-interactions-of-ppar%C3%AE-lbd-with-polyunsaturated-fatty-acids-and-their-anti-inflammatory-metabolites-to-infer-most-potential-binding-moieties
#18
Shalini Muralikumar, Umashankar Vetrivel, Angayarkanni Narayanasamy, Undurti N Das
BACKGROUND: PPARγ is an isoform of peroxisome proliferator-activated receptor (PPAR) belonging to a super family of nuclear receptors. PPARγ receptor is found to play a crucial role in the modulation of lipid and glucose homeostasis. Its commotion has been reported to play a significant role in a broad spectrum of diseases such as type 2 diabetes mellitus, inflammatory diseases, Alzheimer's disease, and in some cancers. Hence, PPARγ is an important therapeutic target. Polyunsaturated fatty acids (PUFAs) and their metabolites (henceforth referred to as bioactive lipids) are known to function as agonists of PPARγ...
January 21, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28103941/involvement-of-the-endocannabinoid-system-in-the-physiological-response-to-transient-common-carotid-artery-occlusion-and-reperfusion
#19
Marina Quartu, Laura Poddighe, Tiziana Melis, Maria Pina Serra, Marianna Boi, Sara Lisai, Gianfranca Carta, Elisabetta Murru, Laura Muredda, Maria Collu, Sebastiano Banni
BACKGROUND: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) may trigger a physiological response in an attempt to preserve tissue and function integrity. There are several candidate molecules among which the endocannabinoid system (ECS) and/or peroxisome-proliferator activated receptor-alpha (PPAR-alpha) may play a role in modulating oxidative stress and inflammation. The aims of the present study are to evaluate whether the ECS, the enzyme cyclooxygenase-2 (COX-2) and PPAR-alpha are involved during BCCAO/R in rat brain, and to identify possible markers of the ongoing BCCAO/R-induced challenge in plasma...
January 19, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28098910/hydrogen-rich-saline-improves-non%C3%A2-alcoholic-fatty-liver-disease-by-alleviating-oxidative-stress-and-activating-hepatic-ppar%C3%AE-and-ppar%C3%AE
#20
Xiao Zhai, Xiao Chen, Jiancan Lu, Yaping Zhang, Xuejun Sun, Qin Huang, Qijin Wang
Non-alcoholic fatty liver disease (NAFLD) comprises a range of liver diseases, between steatosis and non‑alcoholic steatohepatitis and liver cirrhosis, which are closely associated with diabetes mellitus. Previous studies have indicated that oxidative stress is a key factor in the development of NAFLD. Molecular hydrogen (H2) may ameliorate oxidative stress injuries by selectively neutralizing peroxynitrite and hydroxyl radicals. The present study evaluated the effects of H2 on NAFLD in rats and concluded that H2‑rich saline had significant therapeutic effects on NAFLD induced by hyperglycemia and hyperlipidemia, as demonstrated by hematoxylin and eosin and terminal deoxynucleotidyl-transferase‑mediated dUTP nick end labeling staining...
March 2017: Molecular Medicine Reports
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