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https://www.readbyqxmd.com/read/29686697/ppar-%C3%AE-antagonizes-hypoxia-induced-activation-of-hepatic-stellate-cell-through-cross-mediating-pi3k-akt-and-cgmp-pkg-signaling
#1
Qinghui Zhang, Shihao Xiang, Qingqian Liu, Tao Gu, Yongliang Yao, Xiaojie Lu
Background and Aims: Accumulating evidence reveals that PPAR γ plays a unique role in the regulation of hepatic fibrosis and hepatic stellate cells (HSCs) activation. This study was aimed at investigating the role of PPAR γ in hypoxia-induced hepatic fibrogenesis and its possible mechanism. Methods: Rats used for CCl4-induced hepatic fibrosis model were exposed to hypoxia for 8 hours each day. Rats exposed to hypoxia were treated with or without the PPAR γ agonist rosiglitazone...
2018: PPAR Research
https://www.readbyqxmd.com/read/29680740/moringa-concanensis-nimmo-ameliorates-hyperglycemia-in-3t3-l1-adipocytes-by-upregulating-ppar-%C3%AE-c-ebp-%C3%AE-via-akt-signaling-pathway-and-stz-induced-diabetic-rats
#2
Brindha Banu Balakrishnan, Kalaivani Krishnasamy, Ki Choon Choi
Moringa concanensis Nimmo is a medicinal plant for treating various human illnesses including menstrual pain, high blood pressure, jaundice, inflammation, pain, fever, sore eyes, and cholesterol in Indian folk medicine. Despite its versatility, its antihyperglycemic mechanism of action (in vitro and in vivo) remains unclear. Therefore, in this study we developed the possible antihyperglycemic mechanism of action in 3T3-L1 cells by evaluating mRNA and protein expression, which are associated with adipogenesis and lipogenesis (insulin sensitizer)...
April 19, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29679493/ppars-and-pain
#3
REVIEW
Bright N Okine, Jessica C Gaspar, David P Finn
Chronic pain is a common cause of disability worldwide and remains a global health and socioeconomic challenge. Current analgesics are either ineffective in a significant proportion of patients with chronic pain, or associated with significant adverse side effects. The peroxisome proliferator-activated receptors (PPARs), a family of nuclear hormone transcription factors, have emerged as important modulators of pain in preclinical studies and therefore a potential therapeutic target for the treatment of pain...
April 21, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29678641/liver-directed-microrna-7a-depletion-induces-nonalcoholic-fatty-liver-disease-by-stabilizing-yy1-mediated-lipogenic-pathways-in-zebrafish
#4
Chi-Yu Lai, Chiu-Ya Lin, Chia-Chun Hsu, Kun-Yun Yeh, Guor Mour Her
Nonalcoholic fatty liver disease (NAFLD) has been associated with the function and changes in expression levels of microRNAs (miRs). MiR-7 has been proven to play an important role in many cellular processes; however, its functions in the context of liver lipogenesis remain unknown. We applied the microRNA-sponge (miR-SP) technology and generated transgenic miR-7a-SP models (hC7aSP and bC7aSP), which disrupted the activities of hepatic miR-7a and induced the early onset of NAFLD and nonalcoholic steatohepatitis (NASH) in zebrafish...
April 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29674209/possible-mechanisms-underlying-fatty-liver-in-a-rat-model-of-male-hypogonadism-a-protective-role-for-testosterone
#5
Hussein F Sakr, Abdelaziz M Hussein, Elsayed A Eid, Mahmoud AlKhateeb
AIMS: To investigate the effects of testosterone (Test) deficiency and testosterone replacement therapy (TRT) on the development of non-alcoholic fatty liver disease (NAFLD) and associated peripheral insulin resistance (IR) in male rats and to illustrate the underlying mechanisms of action. MATERIALS AND METHODS: male Sprague Dawley rats were divided into 3 groups as follows: 1) sham-operated group (n=11), 2) ORCD-induced group (n=9) exposed to orchidectomy (ORCD), achieved by complete surgical removal of testicles, and 3) ORCD+ Test treated group (n=10) (11 ng/ mL Test propionate, 3x/week, S...
April 16, 2018: Steroids
https://www.readbyqxmd.com/read/29670247/effects-of-microrna-292-5p-on-myocardial-ischemia-reperfusion-injury-through-the-peroxisome-proliferator-activated-receptor-%C3%AE-%C3%AE-signaling-pathway
#6
Zhen-Dong Zhu, Ji-Yun Ye, Hua Niu, Yu-Mei Ma, Xue-Mei Fu, Zhong-Hua Xia, Xuan Zhang
Ischemia-reperfusion injury (IRI) is a major cause of cardiac damage following various pathological processes, such as free radical damage and cell apoptosis. This study aims to investigate whether microRNA-292-5p (miR-292-5p) protects against myocardial ischemia-reperfusion injury (IRI) via the peroxisome proliferator-activated receptor (PPAR)-α/-γ signaling pathway in myocardial IRI mice models. Mouse models of myocardial IRI were established. Adult male C57BL/6 mice were divided into different groups. The hemodynamic indexes, levels of related inflammatory factors and serum myocardial enzymes, and malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected...
April 18, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29670038/taiwanese-green-propolis-ethanol-extract-delays-the-progression-of-type-2-diabetes-mellitus-in-rats-treated-with-streptozotocin-high-fat-diet
#7
Li-Han Chen, Yi-Wen Chien, Mei-Ling Chang, Chia-Chung Hou, Ching-Hung Chan, Hung-Wei Tang, Hui-Yu Huang
Taiwanese green propolis ethanol extract (TGPE) is produced only in Taiwan and has a different composition from other types of propolis. TGPE is known for its anti-inflammation, anti-oxidation, and anti-microbial properties, but the effects and mechanisms of TGPE in the modulation of diabetes are unclear. In this study, we investigated the effects of TGPE on type 2 diabetes mellitus (T2DM) in a streptozotocin/high-fat-diet (STZ/HFD)-induced T2DM rat model. The results revealed that TGPE delayed the development and progression of T2DM and reduced the severity of β-cell failure...
April 18, 2018: Nutrients
https://www.readbyqxmd.com/read/29669060/plasticizer-di-2-ethylhexyl-phthalate-induces-epithelial-to-mesenchymal-transition-and-renal-fibrosis-in-vitro-and-in-vivo
#8
Cheng-Tien Wu, Ching-Chia Wang, Li-Chen Huang, Shing-Hwa Liu, Chih-Kang Chiang
Plasticizer di-(2-ethylhexyl)phthalate (DEHP) is known as an endocrine disruptor and a peroxisome proliferator. A currently epidemiological study has suggested that daily high di-(2-ethylhexyl)phthalate (DEHP) intake from phthalate-tainted foods in children may be a risk factor for renal dysfunction. DEHP can leach from medical devices such as blood storage bags and the tubing. Long-term exposure to DEHP is associated with nephropathy and exacerbates chronic kidney diseases (CKD) progression. However, the detailed effects and molecular mechanisms remain unclear...
April 14, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29667027/neonatal-overfeeding-impairs-differentiation-potential-of-mice-subcutaneous-adipose-mesenchymal-stem-cells
#9
Isabelle Dias, Ísis Salviano, André Mencalha, Simone Nunes de Carvalho, Alessandra Alves Thole, Laís Carvalho, Erika Cortez, Ana Carolina Stumbo
Nutritional changes in the development (intrauterine life and postnatal period) may trigger long-term pathophysiological complications such as obesity and cardiovascular disease. Metabolic programming leads to organs and tissues modifications, including adipose tissue, with increased lipogenesis, production of inflammatory cytokines, and decreased glucose uptake. However, stem cells participation in adipose tissue dysfunctions triggered by overfeeding during lactation has not been elucidated. Therefore, this study was the first to evaluate the effect of metabolic programming on adipose mesenchymal stem cells (ASC) from mice submitted to overfeeding during lactation, using the litter reduction model...
April 17, 2018: Stem Cell Reviews
https://www.readbyqxmd.com/read/29665659/suppressive-effect-of-4-hydroxy-2-4-hydroxyphenethyl-isoindoline-1-3-dione-on-ovalbumin-induced-allergic-asthma
#10
Jin Huang, Mingzhi Su, Bo-Kyung Lee, Mee-Jeong Kim, Jee H Jung, Dong-Soon Im
4-Hydroxy-2-(4-hydroxyphenethyl)isoindoline-1,3-dione (PD1) is a synthetic phthalimide derivative of a marine compound. PD1 has peroxisome proliferator-activated receptor (PPAR) γ agonistic and anti-inflammatory effects. This study aimed to investigate the effect of PD1 on allergic asthma using rat basophilic leukemia (RBL)-2H3 mast cells and an ovalbumin (OVA)-induced asthma mouse model. In vitro , PD1 suppressed β-hexosaminidase activity in RBL-2H3 cells. In the OVA-induced allergic asthma mouse model, increased inflammatory cells and elevated Th2 and Th1 cytokine levels were observed in bronchoalveolar lavage fluid (BALF) and lung tissue...
April 18, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29665350/pxr-structure-specific-activation-by-hepatotoxic-pyrrolizidine-alkaloids
#11
Claudia Luckert, Albert Braeuning, Alfonso Lampen, Stefanie Hessel-Pras
Pyrrolizidine alkaloids (PAs) comprise a large group of more than 660 secondary metabolites found in more than 6000 plant species worldwide. Acute PA intoxication induces severe liver damage. Chronic exposure to sub-lethal doses may cause cumulative damage or cancer. Nuclear receptor activation often constitutes a molecular event for xenobiotic-induced toxicity. However, so far nothing is known about potential interactions of PAs with nuclear receptors as a toxicological mode of action. Thus, in the present study PA-dependent activation of a comprehensive panel of nuclear receptors (PPARs, LXRα, RARα, RXRα, FXR, CAR, PXR, ERα/β) was investigated using GAL4/UAS-based transactivation reporter gene assays...
April 14, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29661566/lichen-planopilaris-and-frontal-fibrosing-alopecia-as-model-epithelial-stem-cell-diseases
#12
REVIEW
Matthew J Harries, Francisco Jimenez, Ander Izeta, Jonathan Hardman, Sreejith Parameswara Panicker, Enrique Poblet, Ralf Paus
Inflammation-associated, irreversible damage to epithelial stem cells (eSCs) of the hair follicle in their immunologically privileged niche lies at the heart of scarring alopecia, which causes permanent difficult-to-treat hair loss. We propose that the two most common and closely related forms, lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA), provide excellent model diseases for studying the biology and pathology of adult human eSCs in an easily accessible human mini-organ. Emphasising the critical roles for interferon (IFN)-γ and peroxisome proliferator-activated receptor (PPAR)-γ-mediated signalling in immune privilege (IP) collapse and epithelial-mesenchymal transition (EMT) of these eSCs respectively, we argue that these pathways deserve therapeutic targeting in the future management of LPP/FFA and other eSC diseases associated with IP collapse and EMT...
April 13, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29656210/micheliolide-alleviates-hepatic-steatosis-in-db-db-mice-by-inhibiting-inflammation-and-promoting-autophagy-via-ppar-%C3%AE-mediated-nf-%C3%B0%C2%BAb-and-ampk-mtor-signaling
#13
Juan Zhong, Wangqiu Gong, Jing Chen, Yao Qing, Shuyue Wu, Hongbei Li, Chunxi Huang, Yihua Chen, Yuxian Wang, Zhaozhong Xu, Wenting Liu, HongYu Li, Haibo Long
The anti-inflammatory, immunomodulatory, and anticancer effects of micheliolide (MCL) isolated from Michelia champaca were previously reported, but its role and underlying mechanisms in relieving liver steatosis remain unclear. Herein, we investigated the effects of MCL on hepatic steatosis using a db/db mouse model and lipid mixture (LM)-induced AML12 and LO2 cells. The body and liver weights, food consumption, lipid content and liver aminotransferase levels in serum, the lipid content and inflammatory cytokine levels in liver tissue, and the extent of hepatic steatosis in db/db mice were increased compared with those in db/m mice, and these increases were reversed by MCL treatment...
April 12, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29649924/polarization-of-microglia-to-the-m2-phenotype-in-a-ppar-%C3%AE-dependent-manner-attenuates-axonal-injury-induced-by-traumatic-brain-injury-in-mice
#14
Liang Wen, Wen-Dong You, Hao Wang, Yuanyuan Meng, Jun-Feng Feng, Xiaofeng Yang
Increasing evidence indicated that activated microglia play an important role in the inflammatory response following traumatic brain injury (TBI). Inhibiting M1 and stimulating M2 activated microglia have demonstrated protective effects in several animal models of central nervous system diseases. However, it is not clear whether the polarization of microglia to M2 attenuates axonal injury following TBI. In this study, we used a lateral fluid percussion injury device to induce axonal injury in mice. Mice were randomly assigned to the sham, TBI, TBI + rosiglitazone (PPAR-γ agonist), and TBI + GW9662 (PPAR-γ antagonist) groups...
April 13, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29628329/structure-guided-evolution-of-a-2-phenyl-4-carboxyquinoline-chemotype-into-ppar%C3%AE-selective-agonists-new-leads-for-oculovascular-conditions
#15
Xiao-Zheng Dou, Dinesh Nath, Younghwa Shin, Jian-Xing Ma, Adam S Duerfeldt
Small molecule agonism of PPARα represents a promising new avenue for the development of non-invasive treatments for oculovascular diseases like diabetic retinopathy and age-related macular degeneration. Herein we report initial structure-activity relationships for the newly identified quinoline-based PPARα agonist, Y-0452. Preliminary computational studies led to the hypothesis that carboxylic acid transposition and deconstruction of the Y-0452 quinoline system would enhance ligand-protein interactions and better complement the nature of the binding pocket...
April 5, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29619245/selective-deletion-of-ppar%C3%AE-%C3%AE-in-fibroblasts-causes-dermal-fibrosis-by-attenuated-lrg1-expression
#16
Ming Keat Sng, Jeremy Soon Kiat Chan, Ziqiang Teo, Terri Phua, Eddie Han Pin Tan, Jonathan Wei Kiat Wee, Nikki Jun Ning Koh, Chek Kun Tan, Jia Peng Chen, Mintu Pal, Benny Meng Kiat Tong, Ya Lin Tnay, Xuan Rui Ng, Pengcheng Zhu, Shunsuke Chiba, Xiaomeng Wang, Walter Wahli, Nguan Soon Tan
Connective tissue diseases of the skin are characterized by excessive collagen deposition in the skin and internal organs. Fibroblasts play a pivotal role in the clinical presentation of these conditions. Nuclear receptor peroxisome-proliferator activated receptors (PPARs) are therapeutic targets for dermal fibrosis, but the contribution of the different PPAR subtypes are poorly understood. Particularly, the role of fibroblast PPARβ/δ in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPARβ/δ in the fibroblast (FSPCre- Pparb/d -/- ) and interrogated its epidermal and dermal transcriptome profiles...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29617419/ppar-gamma-activation-is-associated-with-reduced-liver-ischemia-reperfusion-injury-and-altered-tissue-resident-macrophages-polarization-in-a-mouse-model
#17
Ivan Linares, Kaveh Farrokhi, Juan Echeverri, Johan Moritz Kaths, Dagmar Kollmann, Matyas Hamar, Peter Urbanellis, Sujani Ganesh, Oyedele A Adeyi, Paul Yip, Markus Selzner, Nazia Selzner
BACKGROUND: PPAR-gamma (γ) is highly expressed in macrophages and its activation affects their polarization. The effect of PPAR-γ activation on Kupffer cells (KCs) and liver ischemia-reperfusion injury (IRI) has not yet been evaluated. We investigated the effect of PPAR-γ activation on KC-polarization and IRI. MATERIALS AND METHODS: Seventy percent (70%) liver ischemia was induced for 60mins. PPAR-γ-agonist or vehicle was administrated before reperfusion. PPAR-γ-antagonist was used to block PPAR-γ activation...
2018: PloS One
https://www.readbyqxmd.com/read/29615345/synthesis-biological-evaluation-and-molecular-docking-investigation-of-benzhydrol-and-indole-based-dual-ppar-%C3%AE-ffar1-agonists
#18
Khaled M Darwish, Ismail Salama, Samia Mostafa, Mohamed S Gomaa, El-Sayed Khafagy, Mohamed A Helal
Type-2 diabetes mellitus is a progressive cluster of metabolic disorders, representing a global public health burden affecting more than 366 million people worldwide. We recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome proliferator activated receptor-γ (PPAR-γ) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures...
March 21, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29614883/bergamottin-inhibits-adipogenesis-in-3t3-l1-cells-and-weight-regulation-in-diet-induced-obese-mice
#19
Jeong-Hyeon Ko, Dongwoo Nam, Jae-Young Um, Sang Hoon Jung, Kwang Seok Ahn
Obesity is a serious and increasing health problem worldwide, and the inhibition of adipogenesis is considered to be a potential therapeutic target for it. Bergamottin (BGM), a component of grapefruit juice, has been reported to regulate lipolysis. However, the physiological role of BGM in obesity has not been evaluated so far. In the present study, we investigated the effects of BGM on obesity in 3T3-L1 cells and in mice fed a high-fat diet (HFD). BGM inhibited adipogenic differentiation of 3T3-L1 cells along with a significant decrease in the lipid content by downregulating the expression of two critical adipogenic factors, CCAAT enhancer-binding protein-alpha (C/EBP[Formula: see text]) and peroxisome proliferator activated receptor-gamma (PPAR[Formula: see text])...
April 4, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29604463/identification-of-differentially-expressed-micrornas-during-preadipocyte-differentiation-in-chinese-crested-duck
#20
Shasha Wang, Yang Zhang, Xiaoya Yuan, Rui Pan, Wencheng Yao, Li Zhong, Qianqian Song, Shenghan Zheng, Zhixiu Wang, Qi Xu, Guobin Chang, Guohong Chen
MicroRNAs (miRNAs) are considered key players in the regulation of a broad range of biological processes. Specifically, miRNAs have been reported to play an important role in the process of adipogenesis. In this study, we constructed a model of adipogenesis by isolating preadipocytes (WCC) derived from adipose tissue and preadipocytes after 72 h differentiation (WCT) in vitro. Deep sequencing of miRNAs expressed in WCT and WCC cells was conducted; we identified 105 differentially expressed miRNA candidates (fifty up-regulated and fifty-five down-regulated)...
March 28, 2018: Gene
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