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Anaïs Briot, Pauline Decaunes, Fanny Volat, Chloé Belles, Muriel Coupaye, Séverine Ledoux, Anne Bouloumié
OBJECTIVE: Adipose tissue (AT) dysfunction associated with obesity or aging is a major cause for lipid redistribution and the progression of cardiometabolic disorders. Our goal is to decipher the contribution of human AT microvascular endothelial cells (ECs) in the maintenance of fatty acid (FA) fluxes and the impact of senescence on their function. APPROACH AND RESULTS: We used freshly isolated primary microvascular ECs from human AT. Our data identified the endothelial FA handling machinery including FATPs (FA transport proteins) FATP1, FATP3, FATP4, and CD36 as well as FABP4 (FA binding protein 4)...
March 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Cui Zhang, Liang Li, Yuanda Jiang, Cuicui Wang, Baoming Geng, Yanqiu Wang, Jianling Chen, Fei Liu, Peng Qiu, Guangjie Zhai, Ping Chen, Renfu Quan, Jinfu Wang
Bone formation is linked with osteogenic differentiation of mesenchymal stem cells (MSCs) in the bone marrow. Microgravity in spaceflight is known to reduce bone formation. In this study, we used a real microgravity environment of the SJ-10 Recoverable Scientific Satellite to examine the effects of space microgravity on the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs). hMSCs were induced toward osteogenic differentiation for 2 and 7 d in a cell culture device mounted on the SJ-10 Satellite...
March 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Yves Mugabo, Mina Sadeghi, Nancy N Fang, Thibault Mayor, Gareth E Lim
Adipogenesis involves a complex signaling network requiring strict temporal and spatial organization of effector molecules. Molecular scaffolds, such as 14-3-3 proteins, facilitate such organization, and we have previously identified 14-3-3ζ as an essential scaffold in adipocyte differentiation. The interactome of 14-3-3ζ is large and diverse, and it is possible that novel adipogenic factors may be present within it, but this possibility has not yet been tested. Herein, we generated mouse embryonic fibroblasts from mice overexpressing a TAP-epitope-tagged 14-3-3ζ molecule...
March 12, 2018: Journal of Biological Chemistry
Claus Uhrenholt Christensen, Emilie Glavind, Karen Louise Thomsen, Yong Ook Kim, Sara Heebøll, Detlef Schuppan, Stephen Hamilton-Dutoit, Christian Würtz Heegaard, Henning Grønbæk
BACKGROUND AND AIMS: Hepatic cholesterol deposition drives inflammation and fibrosis in non-alcoholic steatohepatitis (NASH). The Niemann-Pick type C2 (NPC2) protein plays an important role in regulating intracellular cholesterol trafficking and homeostasis. We hypothesized that intravenous NPC2 supplementation reduces cholesterol accumulation, hepatic inflammation and fibrogenesis in a nutritional NASH rat model. METHODS: Rats were fed a high-fat, high-cholesterol (HFHC) diet for four weeks resulting in moderately severe NASH...
2018: PloS One
Mengle Shao, Lavanya Vishvanath, Napoleon C Busbuso, Chelsea Hepler, Bo Shan, Ankit X Sharma, Shiuhwei Chen, Xinxin Yu, Yu A An, Yi Zhu, William L Holland, Rana K Gupta
Pathologic expansion of white adipose tissue (WAT) in obesity is characterized by adipocyte hypertrophy, inflammation, and fibrosis; however, factors triggering this maladaptive remodeling are largely unknown. Here, we test the hypothesis that the potential to recruit new adipocytes from Pdgfrβ+ preadipocytes determines visceral WAT health in obesity. We manipulate levels of Pparg, the master regulator of adipogenesis, in Pdgfrβ+ precursors of adult mice. Increasing the adipogenic capacity of Pdgfrβ+ precursors through Pparg overexpression results in healthy visceral WAT expansion in obesity and adiponectin-dependent improvements in glucose homeostasis...
March 1, 2018: Nature Communications
Xiao-Dong Yang, Yi-Wei Qian, Shao-Qing Xu, Da-Yong Wan, Feng-Hua Sun, Sheng-Di Chen, Qin Xiao
INTRODUCTION: Peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α) plays an important role in Parkinson's disease (PD). The aim of the study was to evaluate PGC-1α gene expression in the peripheral blood of PD patients. We also investigated PGC-1α-related gene variants and identified whether they are associated with PGC-1α gene expression. METHODS: 259 PD patients and 253 healthy controls were included in this study. PPARGC1A (the gene encoding PGC-1α) expression levels were tested using real-time PCR...
February 23, 2018: Parkinsonism & related Disorders
Duo Yang, Na Li, Guoying Zhang
Primary adipose-derived stem cells (ADSCs) are a mixture of cell types including preadipocytes having the ability to spontaneously differentiate into adipocytes. The aim of the present study was to compare the spontaneous adipogenic differentiation potential of ADSCs at different passages to determine whether it decreased with continuous cell passages. Mouse ADSCs (mADSCs) were harvested and cells from passages 1 to 5 were used for experiments. The proliferation of mADSCs at different passages was tested using the cell counting kit‑8 assay...
February 16, 2018: Molecular Medicine Reports
Keping Cheng, Aijuan Yang, Xiaohui Hu, Dongbo Zhu, Kaizhong Liu
BACKGROUND This study aimed to investigate the therapeutic effect of curcumin in lipopolysaccharide (LPS) induced neonatal acute lung injury (ALI) and the possibly associated molecular mechanisms. MATERIAL AND METHODS ALI neonatal animal model was established by using LPS. Curcumin and/or peroxisome proliferator-activated receptor γ (PPARγ) inhibitor BADGE (bisphenol A diglycidyl ether) were administrated to animals. Lung edema was evaluated by PaO2 and lung wet/dry weight ratio (W/D) measurements. EMSA was used to determine the PPARγ activity...
February 26, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Jackie K W Chan, Stefanie Bittner, Alex Bittner, Suman Atwal, Wen-Jun Shen, Mohammed Inayathullah, Jayakumar Rajada, Mark R R Nicolls, Fredric B Kraemer, Salman Azhar
To determine the effects of NDGA on metabolic and molecular changes in response to feeding mice typical American fast food or Western diet, mice were fed with ALIOS diet and subjected to metabolic analysis. Male C57BL/6J mice were randomly assigned to: ALIOS, ALIOS + NDGA, or control diet and maintained on the specific diet for 8 weeks. Mice fed ALIOS diet, showed increased body, liver and epididymal fat pad weight, plasma ALT and AST levels (a measure of liver injury), and liver triglyceride (TG) content. Co-administration of NDGA normalized body and epididymal fat pad weight, ALT and AST levels, and liver TG...
February 22, 2018: Journal of Pharmacology and Experimental Therapeutics
Claudio Bellevicine, Roberta Sgariglia, Ilaria Migliatico, Elena Vigliar, Melania D'Anna, Maria Antonia Nacchio, Nicola Serra, Umberto Malapelle, Massimo Bongiovanni, Giancarlo Troncone
BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) includes fine-needle aspiration (FNA) specimens that cannot straightforwardly be classified as benign or malignant. To determine whether morphological subcategorization based on atypia qualifiers and molecular testing could improve malignancy risk stratification of AUS/FLUS patients, this study assessed the correlation between these qualifiers and the molecular alterations commonly harbored by thyroid neoplasms...
February 22, 2018: Cancer Cytopathology
Laura Galbraith, Hing Y Leung, Imran Ahmad
The link between prostate cancer (PC) development and lipid metabolism is well established, with AR intimately involved in a number of lipogenic processes involving SREBP1, PPARG, FASN, ACC, ACLY and SCD1. Recently, there is growing evidence implicating the role of obesity and peri-prostatic adipose tissue (PPAT) in PC aggressiveness and related mortality, suggesting the importance of lipid pathways in both localised and disseminated disease. A number of promising agents are in development to target the lipogenic axis in PC, and the likelihood is that these agents will form part of combination drug strategies, with targeting of multiple metabolic pathways (e...
February 18, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Xiao Dong, Miao Shi, Moonsook Lee, Rafael Toro, Silvia Gravina, Weiguo Han, Shoya Yasuda, Tao Wang, Zhengdong Zhang, Jan Vijg, Yousin Suh, Simon D Spivack
Gene regulatory analysis of highly diverse human tissues in vivo is essentially constrained by the challenge of performing genome-wide, integrated epigenetic and transcriptomic analysis in small selected groups of specific cell types. Here we performed genome-wide bisulfite sequencing and RNA-seq from the same small groups of bronchial and alveolar cells isolated by laser capture microdissection from flash-frozen lung tissue of 12 donors and their peripheral blood T cells. Methylation and transcriptome patterns differed between alveolar and bronchial cells, while each of these epithelia showed more differences from mesodermally-derived T cells...
February 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Zhao-Jun Wang, Hai-Bin Zhang, Cheng Chen, Hao Huang, Jian-Xia Liang
Accumulation of advanced glycation end products (AGEs) in articular cartilage is thought to represent a major risk factor for osteoarthritis development. In this study we aimed to probe the role of AGEs in human chondrocytes and to determine the impact of the peroxisome proliferator-activated receptor-γ (PPARG) on AGEs-induced cell autophagy. Cell viability was measured after human chondrocytes were treated with different concentrations of AGEs with or without the PPARG inhibitor, T0070907, or agonist, pioglitazone...
February 17, 2018: Cell Biology International
Jonathan D Brown, Zachary B Feldman, Sean P Doherty, Jaime M Reyes, Peter B Rahl, Charles Y Lin, Quanhu Sheng, Qiong Duan, Alexander J Federation, Andrew L Kung, Saptarsi M Haldar, Richard A Young, Jorge Plutzky, James E Bradner
Developmental transitions are guided by master regulatory transcription factors. During adipogenesis, a transcriptional cascade culminates in the expression of PPARγ and C/EBPα, which orchestrate activation of the adipocyte gene expression program. However, the coactivators controlling PPARγ and C/EBPα expression are less well characterized. Here, we show the bromodomain-containing protein, BRD4, regulates transcription of PPARγ and C/EBPα. Analysis of BRD4 chromatin occupancy reveals that induction of adipogenesis in 3T3L1 fibroblasts provokes dynamic redistribution of BRD4 to de novo super-enhancers proximal to genes controlling adipocyte differentiation...
February 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
Thelma Beatriz González-Castro, Carlos Alfonso Tovilla-Zárate, Isela Esther Juárez-Rojop, Yazmín Hernández-Díaz, María Lilia López-Narváez, Candelario Rodríguez-Pérez, Yahaira Karina González-Hernández, Miguel Ángel Ramos-Méndez
AIM: Investigate the correlation between paraoxonase 2 (PON2) Ser311Cys polymorphism as well as the peroxisome proliferator-activated receptor gamma (PPARG) His477His polymorphism and the susceptibility to development of coronary heart diseases (CHD) through a meta-analysis. METHODS: Odds ratio and the corresponding 95% CI were used to assess the results. We included 7476 CHD patients and 8504 healthy controls. All the statistical analyses were performed by Comprehensive Meta-Analysis software (CMA, version 2...
February 14, 2018: Biomarkers in Medicine
Isabel Amendoeira, Tiago Maia, Manuel Sobrinho-Simões
The 2017 edition of the WHO book on Classification of Tumours of Endocrine Organs includes a new section entitled 'Other encapsulated follicular-patterned thyroid tumours', in which the newly created NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features) is identified and described in detail. Despite deleting the word 'carcinoma' from its name, NIFTP is not a benign tumor either and is best regarded as a neoplasm with 'very low malignant potential'. The main goal of the introduction of NIFTP category is to prevent overdiagnosis and overtreatment...
April 2018: Endocrine-related Cancer
Concha Nieto, Rafael Bragado, Cristina Municio, Elena Sierra-Filardi, Bárbara Alonso, María M Escribese, Jorge Domínguez-Andrés, Carlos Ardavín, Antonio Castrillo, Miguel A Vega, Amaya Puig-Kröger, Angel L Corbí
GM-CSF promotes the functional maturation of lung alveolar macrophages (A-MØ), whose differentiation is dependent on the peroxisome proliferator-activated receptor gamma (PPARγ) transcription factor. In fact, blockade of GM-CSF-initiated signaling or deletion of the PPARγ-encoding gene PPARG leads to functionally defective A-MØ and the onset of pulmonary alveolar proteinosis. In vitro , macrophages generated in the presence of GM-CSF display potent proinflammatory, immunogenic and tumor growth-limiting activities...
2018: Frontiers in Immunology
Jingcheng Yu, Ronald J Koenig
PPARγ is widely expressed at low levels and regulates many physiological processes. In mice and humans, there is evidence that PPARγ can function as a tumor suppressor. A PAX8-PPARγ fusion protein (PPFP) is oncogenic in a subset of thyroid cancers, suggesting that inhibition of endogenous PPARγ function by the fusion protein could contribute to thyroid oncogenesis. However, the function of PPARγ within thyrocytes has never been directly tested. Therefore, we have created a thyroid-specific genetic knockout of murine Pparg and have studied thyroid biology in these mice...
February 5, 2018: Endocrinology
Li Liu, Na Si, YiCong Ma, DongYu Ge, Xue Yu, AngRan Fan, Xu Wang, JingHong Hu, Peng Wei, Long Ma, ZiWei Chen, Qian Zhang, CuiLing Feng
BACKGROUND Anti-tumor properties of hydroxysafflor-yellow A (HSYA) have been recently revealed, as a series of apoptotic factors were confirmed to be regulated by HSYA and associated with peroxisome proliferator-activated receptor Gamma (PPARγ). In this study, we investigated the cell apoptosis mechanism of HSYA via activated PPARγ signal in human gastric carcinoma cells. MATERIAL AND METHODS BGC-823 cells were cultured and divided into 5 independent groups: Tumor, HSYA, HSYA+PPARγ inhibitor (GW9662), and PPARg agonist (RGZ), RGZ+GW9662...
February 8, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Wendy Campos-Perez, Nathaly Torres-Castillo, Mariana Perez-Robles, Jose Francisco Muñoz-Valle, Barbara Vizmanos-Lamotte, Erika Martinez-Lopez
BACKGROUND/AIM: One of the beneficial effects associated with vitamin E intake is the enhancement of peroxisome proliferator-activated receptor gamma (PPARγ) activity and the consequent upregulation of adiponectin expression. The aim of this study was to analyze the adiponectin levels in subjects with the Pro12Ala polymorphism of PPARG according to vitamin E intake. METHODS: A total of 283 subjects were enrolled. Total vitamin E intake was estimated based on a validated 3-day food consumption record and analyzed using Nutritionist ProTM software...
February 2, 2018: Journal of Nutrigenetics and Nutrigenomics
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