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https://www.readbyqxmd.com/read/29667027/neonatal-overfeeding-impairs-differentiation-potential-of-mice-subcutaneous-adipose-mesenchymal-stem-cells
#1
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/29665934/-effect-of-regulating-ppar%C3%AE-by-mtor-signaling-on-adipogenesis-of-bone-marrow-mesenchymal-stem-cells-from-aplastic-anemia
#2
Fang Wei, Wei-Huan Zhang, Xiu-Lian Zhang, Xiao-Jing Ge, Shu-Qin Zhang
OBJECTIVE: To study the effect and mechanism of mTOR signaling on adipogenesis of bone marrow mesenchymal stem cells(BM-MSCs) from aplastic anemia (AA) patients through regulation of PPARγ. METHODS: BM-MSCs were isolated from 24 newly diagnosed AA patients and 24 healthy controls. The surface antigen expression of BM-MSCs was identified by flow cytometry. The capacity of adipogenic differentiation of BM-MSCs was determined by lipid droplets based on Oil Red O staining and by the expression of FABP4 based on Western blot...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665659/suppressive-effect-of-4-hydroxy-2-4-hydroxyphenethyl-isoindoline-1-3-dione-on-ovalbumin-induced-allergic-asthma
#3
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/29665653/upregulation-of-ppar-%C3%AE-mediates-the-renoprotective-effect-of-omega-3-pufa-and-ferulic-acid-in-gentamicin-intoxicated-rats
#4
Nahla E El-Ashmawy, Naglaa F Khedr, Hoda A El-Bahrawy, Sara A Helal
Ferulic acid (FrA) is a natural product containing phenolic compounds. ω-3 PUFA is the major constituent of fish oil. The aim of this study was to investigate the renoprotective role of FrA and FO in gentamicin (GM)-induced nephrotoxicity in rats. Forty four male rats were divided equally into 4 groups: Control group, GM group, FrA + GM group and FO + GM group. Each of the treated groups was injected with GM (40 mg/kg) i.p. for 9 consecutive days. FrA (100 mg/kg) and FO (5 mL/kg) were given to rats orally daily for 10 days prior to GM and then concomitantly with GM for additional 9 days...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29665350/pxr-structure-specific-activation-by-hepatotoxic-pyrrolizidine-alkaloids
#5
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/29663642/oral-administration-of-edible-wakame-seaweed-undaria-pinnatifida-wakame-modifies-glucose-and-lipid-metabolism-in-rats-a-dna-microarray-analysis
#6
Keiko Yoshinaga, Yuji Nakai, Hikari Izumi, Kaz Nagaosa, Tomoko Ishijima, Takahisa Nakano, Keiko Abe
SCOPE: Wakame is an edible seaweed that is a common constituent in the Japanese diet. Previous studies showed that wakame consumption is associated with the prevention of metabolic syndrome, but the molecular mechanisms underlying the protective effects are poorly understood. METHODS AND RESULTS: To determine if the expression of hepatic genes is affected by ingestion of the brown seaweed Undaria pinnatifida (wakame), rats were fed a diet containing 0, 0.1, or 1...
April 16, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29662200/targeting-sphingosine-1-phosphate-lyase-as-an-anabolic-therapy-for-bone-loss
#7
Sarah Weske, Mithila Vaidya, Alina Reese, Karin von Wnuck Lipinski, Petra Keul, Julia K Bayer, Jens W Fischer, Ulrich Flögel, Jens Nelsen, Matthias Epple, Marta Scatena, Edzard Schwedhelm, Marcus Dörr, Henry Völzke, Eileen Moritz, Anke Hannemann, Bernhard H Rauch, Markus H Gräler, Gerd Heusch, Bodo Levkau
Sphingosine-1-phosphate (S1P) signaling influences bone metabolism, but its therapeutic potential in bone disorders has remained unexplored. We show that raising S1P levels in adult mice through conditionally deleting or pharmacologically inhibiting S1P lyase, the sole enzyme responsible for irreversibly degrading S1P, markedly increased bone formation, mass and strength and substantially decreased white adipose tissue. S1P signaling through S1P2 potently stimulated osteoblastogenesis at the expense of adipogenesis by inversely regulating osterix and PPAR-γ, and it simultaneously inhibited osteoclastogenesis by inducing osteoprotegerin through newly discovered p38-GSK3β-β-catenin and WNT5A-LRP5 pathways...
April 16, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29662003/ppar-agonists-and-metabolic-syndrome-an-established-role
#8
REVIEW
Margherita Botta, Matteo Audano, Amirhossein Sahebkar, Cesare R Sirtori, Nico Mitro, Massimiliano Ruscica
Therapeutic approaches to metabolic syndrome (MetS) are numerous and may target lipoproteins, blood pressure or anthropometric indices. Peroxisome proliferator-activated receptors (PPARs) are involved in the metabolic regulation of lipid and lipoprotein levels, i.e., triglycerides (TGs), blood glucose, and abdominal adiposity. PPARs may be classified into the α, β/δ and γ subtypes. The PPAR-α agonists, mainly fibrates (including newer molecules such as pemafibrate) and omega-3 fatty acids, are powerful TG-lowering agents...
April 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29661566/lichen-planopilaris-and-frontal-fibrosing-alopecia-as-model-epithelial-stem-cell-diseases
#9
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/29660719/assessment-of-endocrine-disruptors-effects-on-zebrafish-danio-rerio-embryos-by-untargeted-lc-hrms-metabolomic-analysis
#10
Elena Ortiz-Villanueva, Joaquim Jaumot, Rubén Martínez, Laia Navarro-Martín, Benjamin Piña, Romà Tauler
Bisphenol A (BPA), perfluorooctane sulfonate (PFOS), and tributyltin (TBT) are emerging endocrine disruptors (EDCs) with still poorly defined mechanisms of toxicity and metabolic effects in aquatic organisms. We used an untargeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) metabolomic approach to study the effects of sub-lethal doses of these three EDCs on the metabolic profiles of zebrafish embryos exposed from 48 to 120hpf (hours post fertilization). Advanced chemometric data analysis methods were used to reveal effects on the subjacent regulatory pathways...
April 13, 2018: Science of the Total Environment
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
#11
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/29651202/a-narrative-review-of-potential-future-antidiabetic-drugs-should-we-expect-more
#12
REVIEW
Gaurav Chikara, Pramod Kumar Sharma, Pradeep Dwivedi, Jaykaran Charan, Sneha Ambwani, Surjit Singh
Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential...
April 2018: Indian Journal of Clinical Biochemistry: IJCB
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
#13
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
#14
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/29626530/high-fat-diet-affects-gut-nutrients-transporters-in-hypo-and-hyperthyroid-mice-by-ppar-a-independent-mechanism
#15
Mariana Cerqueira Losacco, Carolina Fernanda Theodora de Almeida, Andressa Harumi Torelli Hijo, Paula Bargi-Souza, Patricia Gama, Maria Tereza Nunes, Francemilson Goulart-Silva
AIMS: High fat diet consumes and thyroid hormones (THs) disorders may affect nutrients metabolism, but their impact on the absorptive epithelium, the first place of nutrients access, remains unknown. Our aim was to evaluate the intestinal morphology and nutrients transporters content in mice fed standard (LFD) or high fat (HFD) diets in hypo or hyperthyroidism-induced condition. MATERIAL AND METHODS: C57BL/6 male mice fed LFD or HFD diets for 12 weeks, followed by saline, PTU (antithyroid drug) or T3 treatment up to 30 days...
April 4, 2018: Life Sciences
https://www.readbyqxmd.com/read/29626477/chronic-cold-exposure-results-in-subcutaneous-adipose-tissue-browning-and-altered-global-metabolism-in-qinghai-tibetan-plateau-pika-ochotona-curzoniae
#16
Jia Li, Quanyu Yang, Zhenzhong Bai, Gregg L Semenza, Ri-Li Ge
The plateau pika (Ochotona curzoniae), one of the indigenous animals of the Qinghai-Tibet Plateau, is adapted to life in a cold and hypoxic environment. We conducted a series of genomic, proteomic and morphological studies to investigate whether changes in energy metabolism contribute to adaptation of the plateau pika to cold stress by analyzing summer and winter cohorts. The winter group showed strong morphological and histological features of brown adipose tissue (BAT) in subcutaneous white adipose tissue (sWAT)...
April 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29625788/clinicopathological-and-predictive-significance-of-sirt1-and-peroxisome-proliferator-activated-receptor-gamma-in-esophageal-squamous-cell-carcinoma-the-correlation-with-egfr-and-survivin
#17
Fei Han, Suxia Zhang, Jun Liang, Weizhe Qiu
SIRT1 (silent mating type information regulation 2 homolog 1) is an enzyme that deacetylates proteins that contributes to cell survival and angiogenesis. Peroxisome proliferator-activated receptor Ƴ (PPAR Ƴ) is a member of the nuclear steroid hormone receptor superfamily and regulates cell apoptosis and proliferation. The functional roles of SIRT1 and PPAR Ƴ in tumor progression remain controversy. This study aims to investigate the roles of SIRT1 and PPAR Ƴ in esophageal squamous cell carcinoma (ESCC), as well as correlation with expression of EGFR and Survivin...
March 22, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29621178/assessment-of-the-pro12ala-polymorphism-in-the-ppar-%C3%AE-2-gene-among-type-2-diabetes-patients-in-a-nigerian-population
#18
Godwill Azeh Engwa, Friday Nweke Nwalo, Venatus Osita Chiezey, Marian N Unachukwu, Opeolu Oyejide Ojo, Benjamin Ewa Ubi
The association between the Pro12Ala polymorphism of the PPARγ2 gene, type 2 diabetes (T2D), and obesity in certain ethnic populations has been reported. However, this relationship has not yet been described among diabetes patients in Nigeria. This study investigated the relationship between the Pro12Ala polymorphism in the PPARγ2 gene, obesity, and lipid abnormalities characterizing T2D among patients in Nigeria. This case-control study recruited 73 T2D and 75 non-diabetic (ND) patients. Demographic and clinical data were collected and blood glucose levels together with serum lipid profile for patients were measured...
April 5, 2018: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/29621036/comparative-evaluation-of-gemcabene-and-ppar-ligands-in-transcriptional-assays-of-peroxisome-proliferator-activated-receptors-implication-for-the-treatment-of-hyperlipidemia-and-cardiovascular-disease
#19
Charles L Bisgaier, Daniela C Oniciu, Rai Ajit K Srivastava
Gemcabene, a late-stage clinical candidate, has shown efficacy for LDL-C, non-HDL cholesterol, apoB, triglycerides and hsCRP reduction, all risk factors for cardiovascular disease (CVD). In rodents, gemcabene showed changes in targets, including apoC-III, apoA-I, peroxisomal enzymes, considered regulated via PPAR gene activation, suggesting a PPAR-mediated mechanism of action for the observed hypolipidemic effects observed in rodents and humans. In the current study, the gemcabene agonist activity against PPAR subtypes of human, rat and mouse were compared to known lipid lowering PPAR activators...
March 21, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29619245/selective-deletion-of-ppar%C3%AE-%C3%AE-in-fibroblasts-causes-dermal-fibrosis-by-attenuated-lrg1-expression
#20
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
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