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https://www.readbyqxmd.com/read/29458019/raffinose-from-costus-speciosus-attenuates-lipid-synthesis-through-modulation-of-ppars-srebp1c-and-improves-insulin-sensitivity-through-pi3k-akt
#1
Muthukumaran Padmanaban, Thiyagarajan Gopal, Arun Babu Rajendran, Baddireddi Subhadra Lakshmi
Among several metabolic disorders, the pathogenesis of insulin resistance is considered to be multifactorial. Raffinose, an oligosaccharide isolated from the rhizome of Costus speciosus showed ≤50% inhibition of lipid accumulation in differentiated HepG2 and 3T3-L1 cells through exhibiting partial agonism to PPARγ, and, an enhanced secretion of adiponectin in 3T3-L1 adipocytes. Raffinose was also observed to attenuate the expression of SREBP1c, ACC and FAS which are involved in the fatty acid synthesis. A corresponding upregulation of PPARα and ACO involved in fatty acid oxidation was observed in steatotic HepG2 hepatocytes and 3T3-L1 adipocytes...
February 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29456675/correlation-between-ppar-%C3%AE-methylation-level-in-peripheral-blood-and-atherosclerosis-of-nafld-patients-with-dm
#2
Jianghua Ju, Qingxian Huang, Jing Sun, Xiaoyun Zhao, Xiuli Guo, Yongcheng Jin, Wenjie Ma, Wenhui Wang
We investigated the correlation between the methylation levels of peroxisome proliferator-activated receptor-α (PPAR-α) in the peripheral blood and atherosclerosis in patients with nonalcoholic fatty liver disease (NAFLD) with diabetes mellitus (DM). A total of 50 normal subjects (group N) and 50 NAFLD patients with DM (group M) were selected at Qilu Hospital of Shandong University. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in groups N and M were detected...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29455954/the-peroxisome-proliferator-activated-receptor-%C3%AE-is-dispensable-for-cold-induced-adipose-tissue-browning-in-mice
#3
Merel Defour, Wieneke Dijk, Philip Ruppert, Emmani B M Nascimento, Patrick Schrauwen, Sander Kersten
OBJECTIVE: Chronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue (BAT), a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPARα) in cold-induced browning. Here we aimed to investigate the importance of PPARα in driving transcriptional changes during cold-induced browning in mice. METHODS: Male wildtype and PPARα-/- mice were housed at thermoneutrality (28 °C) or cold (5 °C) for 10 days...
February 9, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29454501/postoperative-inflammation-and-insulin-resistance-in-relation-to-body-composition-adiposity-and-carbohydrate-treatment-a-randomised-controlled-study
#4
Nilanjana Tewari, Sherif Awad, František Duška, Julian P Williams, Andrew Bennett, Ian A Macdonald, Dileep N Lobo
BACKGROUND & AIMS: The aims of this study were to identify whether differences in distribution of adipose tissue and skeletal muscle in obese and non-obese individuals contribute to the magnitude of the postoperative inflammatory response and insulin resistance, with and without preoperative treatment with carbohydrate drinks. METHODS: Thirty-two adults (16 obese/16 non-obese) undergoing elective major open abdominal surgery participated in this 2 × 2 factorial, randomised, double-blind, placebo-controlled study...
February 14, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29453696/interrelationship-between-diabetes-mellitus-and-heart-failure-the-role-of-peroxisome-proliferator-activated-receptors-in-left-ventricle-performance
#5
REVIEW
Evangelos Oikonomou, Konstantinos Mourouzis, Petros Fountoulakis, Georgios Angelos Papamikroulis, Gerasimos Siasos, Alexis Antonopoulos, Georgia Vogiatzi, Sotiris Tsalamadris, Manolis Vavuranakis, Dimitris Tousoulis
Heart failure (HF) is a common cardiac syndrome, whose pathophysiology involves complex mechanisms, some of which remain unknown. Diabetes mellitus (DM) constitutes not only a glucose metabolic disorder accompanied by insulin resistance but also a risk factor for cardiovascular disease and HF. During the last years though emerging data set up, a bidirectional interrelationship between these two entities. In the case of DM impaired calcium homeostasis, free fatty acid metabolism, redox state, and advance glycation end products may accelerate cardiac dysfunction...
February 17, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29453462/gq-11-a-new-ppar-agonist-improves-obesity-induced-metabolic-alterations-in-ldlr-mice
#6
Jacqueline C Silva, Edson M de Oliveira, Walter M Turato, Gustavo H G Trossini, Vinícius G Maltarollo, Marina G R Pitta, Ivan R Pitta, Beatriz de Las Heras, Lisardo Boscá, Martina Rudnicki, Dulcineia S P Abdalla
BACKGROUND: Obesity and insulin resistance/diabetes are important risk factors for cardiovascular diseases and demand safe and efficacious therapeutics. OBJECTIVE: To assess the effects of a new thiazolidine compound-GQ-11-on obesity and insulin resistance induced by a diabetogenic diet in LDL receptor-deficient (LDLr -/- ) mice. METHODS: Molecular docking simulations of GQ-11, PPARα and PPARγ structures were performed. Male C57BL/6J LDLr -/- mice fed a diabetogenic diet for 24 weeks were treated with vehicle, GQ-11 or pioglitazone or (20 mg/kg/day) for 28 days by oral gavage...
January 30, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29450204/ppars-key-regulators-of-airway-inflammation-and-potential-therapeutic-targets-in-asthma
#7
Asoka Banno, Aravind T Reddy, Sowmya P Lakshmi, Raju C Reddy
Asthma affects approximately 300 million people worldwide, significantly impacting quality of life and healthcare costs. While current therapies are effective in controlling many patients' symptoms, a large number continue to experience exacerbations or treatment-related adverse effects. Alternative therapies are thus urgently needed. Accumulating evidence has shown that the peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone receptors, comprising PPARα, PPARβ/δ, and PPARγ, is involved in asthma pathogenesis and that ligand-induced activation of these receptors suppresses asthma pathology...
2018: Nuclear Receptor Research
https://www.readbyqxmd.com/read/29449830/screening-for-ppar-non-agonist-ligands-followed-by-characterization-of-a-hit-am-879-with-additional-no-adipogenic-and-cdk5-mediated-phosphorylation-inhibition-properties
#8
Helder Veras Ribeiro Filho, Natália Bernardi Videira, Aline Villanova Bridi, Thais Helena Tittanegro, Fernanda Aparecida Helena Batista, José Geraldo de Carvalho Pereira, Paulo Sérgio Lopes de Oliveira, Marcio Chaim Bajgelman, Albane Le Maire, Ana Carolina Migliorini Figueira
Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of a nuclear receptor superfamily and acts as a ligand-dependent transcription factor, playing key roles in maintenance of adipose tissue and in regulation of glucose and lipid homeostasis. This receptor is the target of thiazolidinediones, a class of antidiabetic drugs, which improve insulin sensitization and regulate glycemia in type 2 diabetes. Despite the beneficial effects of drugs, such as rosiglitazone and pioglitazone, their use is associated with several side effects, including weight gain, heart failure, and liver disease, since these drugs induce full activation of the receptor...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29446942/design-synthesis-and-evaluation-of-a-novel-series-of-indole-sulfonamide-peroxisome-proliferator-activated-receptors-ppar-%C3%AE-%C3%AE-%C3%AE-triple-activators-discovery-of-lanifibranor-a-new-anti-fibrotic-clinical-candidate
#9
Benaissa Boubia, Olivia Poupardin, Martine Barth, Jean Binet, Philippe Peralba, Laurent Mounier, Elise Jacquier, Emilie Gauthier, Valerie Lepais, Maryline Chatar, Stephanie Ferry, Anne Thourigny, Fabrice Guillier, Jonathan Llacer, Jerome Amaudrut, Pierre Dodey, Olivier Lacombe, Philippe Masson, Christian Montalbetti, Guillaume Wettstein, Jean Michel Luccarini, Christiane Legendre, Jean Louis Junien, Pierre Broqua
Here we describe the identification and synthesis of novel indole sulfonamide derivatives that activate the three peroxisome proliferator activated receptor (PPAR) isoforms. Starting with a PPARα activator, compound 4, identified during a high throughput screening (HTS) of our proprietary screening library, a systematic optimization led to the discovery of lanifibranor (IVA337) 5, a moderately potent and well balanced pan PPAR agonist with an excellent safety profile. In vitro and in vivo, compound 5 demonstrated strong activity in models that are relevant to NonAlcoholic SteatoHepatitis (NASH) pathophysiology suggesting therapeutical potential for NASH patients...
February 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29445073/adiponectin-deficiency-induced-diabetes-increases-tnf%C3%AE-and-ffa-via-downregulation-of-ppar%C3%AE
#10
Haruo Hashimoto, Masafumi Yamamoto, Emika Sugiura, Hayato Abe, Takahiro Kagawa, Motohito Goto, Ri-Ichi Takahashi, Toshio Akimoto, Hiroshi Suemizu
Expression of peroxisome proliferator-activated receptor (PPAR) α was investigated in adiponectin knockout mice to elucidate the relationship between PPARα and adiponectin deficiency-induced diabetes. Adiponectin knockout (Adp -/- ) mice were generated by gene targeting. Glucose tolerance test (GTT), insulin tolerance test (ITT), and organ sampling were performed in Adp -/- mice at the age of 10 weeks. PPARα, insulin, triglyceride, free fatty acid (FFA), and tumor necrosis factor α (TNFα) were analyzed from the sampled organs...
February 14, 2018: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29441829/role-of-peroxisome-proliferator-activated-receptor-gamma-activation-on-visfatin-advanced-glycation-end-products-and-renal-oxidative-stress-in-obesity-induced-type-2-diabetes-mellitus
#11
A Tabassum, T Mahboob
The present study focused on the role of peroxisome proliferator-activated receptor-gamma (PPAR-γ) activation on renal oxidative damages, serum visfatin, and advanced glycation end products (AGEs) in high-fat diet (HFD)-induced type 2 diabetes mellitus. Following the institutional animal ethics committee guidelines, Wistar rats were categorized into five groups: group 1: fed on a normal rat diet; group 2: HFD-induced obese rats (HFD for 8 weeks); group 3: HFD-fed rats treated with rosiglitazone (RSG; 3 mg/kg orally for 7 days); group 4: T2DM rats induced by HFD and low dose of streptozotocin (i...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29441719/azd1208-a-pan-pim-kinase-inhibitor-inhibits-adipogenesis-and-induces-lipolysis-in-3t3-l1-adipocytes
#12
Yu-Kyoung Park, Brice Wilfried Obiang-Obounou, Kyung-Bok Lee, Jong-Soon Choi, Byeong-Churl Jang
The proviral integration moloney murine leukaemia virus (Pim) kinases, consisting of Pim-1, Pim-2 and Pim-3, are involved in the control of cell growth, metabolism and differentiation. Pim kinases are emerging as important mediators of adipocyte differentiation. AZD1208 is a pan-Pim kinase inhibitor and is known for its anti-cancer activity. In this study, we investigated the effect of AZD1208 on adipogenesis and lipolysis in 3T3-L1 cells, a murine preadipocyte cell line. AZD1208 markedly suppressed lipid accumulation and reduced triglyceride contents in differentiating 3T3-L1 cells, suggesting the drug's anti-adipogenic effect...
February 14, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29436615/identification-and-validation-of-the-role-of-matrix-metalloproteinase-1-in-cervical-cancer
#13
Run Tian, Xiaofang Li, Yan'e Gao, Yue Li, Pei Yang, Kunzheng Wang
Lymph node (LN) metastasis at an early stage of cervical cancer is often an indicator of poor prognosis and is critical for subsequent adjuvant therapy. The current study aimed to identify aberrant gene signatures and biomarkers of metastasis for patients with cervical cancer. RNA-sequencing data of 132 LN negative (N0) and 60 LN positive (N1) cervical cancer samples obtained from The Cancer Genome Atlas database were analyzed. Differentially expressed genes were identified using R packages 'edgeR' and 'limma'...
February 7, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29435026/dha-induces-apoptosis-of-human-malignant-breast-cancer-tissues-by-the-tlr-4-ppar-%C3%AE-pathways
#14
Lijing Geng, Wei Zhou, Bing Liu, Xinyun Wang, Bo Chen
Docosahexaenoic acid (DHA) oil is an important polyunsaturated fatty acid for the human body. Evidence has demonstrated that DHA is beneficial for inhibiting mammary carcinogenesis. However, the mechanisms of DHA mediating apoptosis induction have not been fully elucidated. Thus, in the present study, the activity levels of total-superoxide dismutase (t-SOD), catalase (CAT), glutathione-peroxidase (GSH-PX) and the concentration of malondialdehyde (MDA) were determined in DHA oil-treated human malignant breast tissues...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434731/correlation-between-ppar-%C3%AE-methylation-level-in-peripheral-blood-and-inflammatory-factors-of-nafld-patients-with-dm
#15
Jianghua Ju, Qingxian Huang, Jing Sun, Yongcheng Jin, Wenjie Ma, Xiaohui Song, Huibo Sun, Wenhui Wang
The correlation between the methylation levels of peroxisome proliferator-activated receptor-α (PPAR-α) in the peripheral blood and the inflammatory factors associated with non-alcoholic fatty liver disease (NAFLD) patients with diabetes mellitus (DM) was investigated. Thirty-two samples of normal liver tissues (group N) and 35 samples of liver tissues from NAFLD patients with DM (group M) were used for the present study. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were measured using commercially available kits...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434210/epigenetic-modulation-of-fgf21-in-the-perinatal-mouse-liver-ameliorates-diet-induced-obesity-in-adulthood
#16
Xunmei Yuan, Kazutaka Tsujimoto, Koshi Hashimoto, Kenichi Kawahori, Nozomi Hanzawa, Miho Hamaguchi, Takami Seki, Makiko Nawa, Tatsuya Ehara, Yohei Kitamura, Izuho Hatada, Morichika Konishi, Nobuyuki Itoh, Yoshimi Nakagawa, Hitoshi Shimano, Takako Takai-Igarashi, Yasutomi Kamei, Yoshihiro Ogawa
The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α-dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood...
February 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29434029/de-novo-fatty-acid-synthesis-by-schwann-cells-is-essential-for-peripheral-nervous-system-myelination
#17
Laura Montani, Jorge A Pereira, Camilla Norrmén, Hartmut B F Pohl, Elisa Tinelli, Martin Trötzmüller, Gianluca Figlia, Penelope Dimas, Belinda von Niederhäusern, Rachel Schwager, Sebastian Jessberger, Clay F Semenkovich, Harald C Köfeler, Ueli Suter
Myelination calls for a remarkable surge in cell metabolism to facilitate lipid and membrane production. Endogenous fatty acid (FA) synthesis represents a potentially critical process in myelinating glia. Using genetically modified mice, we show that Schwann cell (SC) intrinsic activity of the enzyme essential for de novo FA synthesis, fatty acid synthase (FASN), is crucial for precise lipid composition of peripheral nerves and fundamental for the correct onset of myelination and proper myelin growth. Upon FASN depletion in SCs, epineurial adipocytes undergo lipolysis, suggestive of a compensatory role...
February 6, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29433142/ppar-%C3%AE-agonist-improves-hyperglycemia-induced-oxidative-stress-in-pancreatic-cells-by-potentiating-antioxidant-defense-system
#18
Habib Yaribeygi, Mohammad Taghi Mohammadi, Amirhossein Sahebkar
BACKGROUND: Diabetes-induced oxidative stress has an essential role in pancreatic cells dysfunction. The present study aimed to evaluate whether peroxisome proliferator activated receptor- alpha (PPAR-α) induction by fenofibrate counterbalances oxidative stress in pancreatic cells. METHODS: In this in vivo study, male Wistar rats were randomly divided into four groups as normal, normal treated, diabetic and diabetic treated groups (n=6 in each group). Diabetes was induced by a single intravenous injection of streptozotocin (45 mg/kg)...
February 12, 2018: Drug Research
https://www.readbyqxmd.com/read/29432661/is-pulmonary-vascular-disease-reversible-with-ppar-%C3%A9-agonists
#19
Peter Afdal, Antoine F AbdelMassih
Severe angio-obliterative pulmonary vascular disease (PAH) remains a disease characterized by great morbidity and shortened survival. Unfortunately, the only currently available treatments for angio-obliterative changes are palliative in the form of pulmonary vasodilators evolving from the phosphodiesterase inhibitor sildenafil to endothelin receptor antagonist: Bosentan; while the only definitive treatment is lung transplantation which remains dependent on the availability of donors and the transplant policies which vary widely from a country to another...
February 12, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/29429540/sodium-butyrate-modulates-adipocyte-expansion-adipogenesis-and-insulin-receptor-signaling-by-upregulation-of-ppar-%C3%AE-in-obese-apo-e-knockout-mice
#20
Edenil Costa Aguilar, Josiane Fernandes da Silva, Juliana Maria Navia-Pelaez, Alda Jusceline Leonel, Lorrayne Gonçalves Lopes, Zélia Menezes-Garcia, Adaliene Versiani Matos Ferreira, Luciano Dos Santos Aggum Capettini, Lilian G Teixeira, Virginia Soares Lemos, Jacqueline I Alvarez-Leite
OBJECTIVES: Studies suggest that sodium butyrate reduces obesity-associated inflammation and insulin resistance in in vitro and in vivo models. Apo E -/- mice have high basal oxidative stress and naturally develop dyslipidemia and atherosclerosis. Because these disorders are present in obesity, the aim of this study was to determine whether Apo E -/- mice could be a more realistic model for studying obesity and insulin resistance. METHODS: We evaluated the action of orally administered sodium butyrate on adipose tissue expansion and insulin resistance using diet-induced obese Apo E -/- mice...
March 2018: Nutrition
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