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Simone Vargas da Silva, Mariana Renovato-Martins, Cristiane Ribeiro-Pereira, Marta Citelli, Christina Barja-Fidalgo
OBJECTIVE: To investigate the role of obesity on the bone marrow microenvironment and evaluate its possible impact on the adipogenic potential of mesenchymal stem cells (MSC). METHODS: C57BL/6 male mice were fed with a high-fat diet (HFD) for 10 weeks. Femurs and tibiae were collected, and bone marrow mesenchymal stem cells (BM-MSC) were isolated and analyzed for proliferative potential, immunophenotype, and expression of adipogenesis markers. Their capacity to produce extracellular matrix proteins and proinflammatory cytokines in vitro was also evaluated...
October 18, 2016: Obesity
Younho Han, Chae Yul Kim, Heesun Cheong, Kwang Youl Lee
Osterix is a novel bone-related transcription factor involved in osteoblast differentiation, and bone maturation. Because a reciprocal relationship exists between adipocyte and osteoblast differentiation of bone marrow derived mesenchymal stem cells, we hypothesized that Osterix might have a role in adipogenesis. Ablation of Osterix enhanced adipogenesis in 3T3-L1 cells, whereas overexpression suppressed this process and inhibited the expression of adipogenic markers including CCAAT/enhancer-binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ)...
October 18, 2016: Scientific Reports
Tomasz Bednarski, Adam Olichwier, Agnieszka Opasinska, Aleksandra Pyrkowska, Ana-Maria Gan, James M Ntambi, Pawel Dobrzyn
Stearoyl-CoA desaturase 1 (SCD1) has recently been shown to be a critical control point in the regulation of cardiac metabolism and function. Peroxisome proliferator-activated receptor α (PPARα) is an important regulator of myocardial fatty acid uptake and utilization. The present study used SCD1 and PPARα double knockout (SCD1(-/-)/PPARα(-/-)) mice to test the hypothesis that PPARα is involved in metabolic changes in the heart that are caused by SCD1 downregulation/inhibition. SCD1 deficiency decreased the intracellular content of free fatty acids, triglycerides, and ceramide in the heart of SCD1(-/-) and SCD1(-/-)/PPARα(-/-) mice...
October 15, 2016: Biochimica et Biophysica Acta
Guangyong Chen, Yangdong Han, Wang He, Feng Liang
In the present study, we evaluated the protective effects of amentoflavone (AMF) against high-fat (HF) diet-induced metabolic dysfunction and focused on the influence of AMF on adipogenic differentiation during 3T3-L1 adipocyte differentiation. For this purpose, male Wistar rats were fed a HF diet or a HF diet with AMF (10 or 50 mg/kg). We found that AMF protected against HF diet-induced metabolic dysfunction in a dose-dependent manner, as evidenced by a decrease in the fasting blood glucose levels, fasting insulin levels and the homeostatic model assessment-insulin resistance index (HOMA‑IR), as well as by a decrease in the glucose level, as shown by the intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test...
October 14, 2016: International Journal of Molecular Medicine
Avik Roy, Madhuchhanda Kundu, Malabendu Jana, Rama K Mishra, Yeni Yung, Chi-Hao Luan, Frank J Gonzalez, Kalipada Pahan
Peroxisome proliferator-activated receptor-α (PPARα) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently we found that PPARα is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here we report the discovery of three endogenous PPARα ligands-3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide-in mouse brain hippocampus. Mass spectrometric detection of these compounds in mouse hippocampal nuclear extracts, in silico interaction studies, time-resolved FRET analyses, and thermal shift assay results clearly indicated that these three compounds served as ligands of PPARα...
October 17, 2016: Nature Chemical Biology
Devaraj Ezhilarasan, Jonathan Evraerts, Sid Brice, Pedro Buc-Calderon, Sivanesan Karthikeyan, Etienne Sokal, Mustapha Najimi
BACKGROUND: Proliferation of hepatic stellate cells (HSCs) play pivotal role in the progression of hepatic fibrosis consequent to chronic liver injury. Silibinin (SBN), a flavonoid compound, has shown to possess cell cycle arresting potential against many actively proliferating cancers cell lines. The objective of this study was to evaluate the anti-proliferative and cell cycle arresting properties of SBN in rapidly proliferating human hepatic stellate LX-2 cell line. METHODS: LX-2 cells were fed with culture medium supplemented with different concentrations of SBN (10, 50 and 100 μM)...
September 2016: Journal of Clinical and Experimental Hepatology
Yong Xie, Zhen-Jie Gu, Mao-Xiong Wu, Tu-Cheng Huang, Jing-Song Ou, Huiping-Son Ni, Mao-Huan Lin, Wo-Liang Yuan, Jing-Feng Wang, Yang-Xin Chen
AIMS: Adverse cardiovascular effects induced by peroxisome proliferator activator receptor-γ (PPAR-γ) activation were observed in clinical setting. But the underlying mechanism is unclear. Now, transgenic mice with cardiac specific peroxisome proliferator activator receptor-γ overexpression (TG-PPAR-γ) were used to explore the possible mechanisms. MATERIALS AND METHODS: Cardiac tissues from TG-PPAR-γ mice, a PPAR-γ over-expressing human cardiomyocyte line AC16 cell, and PPAR-γ agonist-treated primary cardiomyocytes were used to evaluate the expression of cardiac calcium regulatory proteins as sarcoplasmic reticulum Ca(2+) ATPase, Na(+)/Ca(2+)exchanger 1, ryanodine receptor 2 and phospholamban...
October 13, 2016: Life Sciences
Adam Kawałek, Chandhuru Jagadeesan, Ida J van der Klei
The non-bilayer forming lipids cardiolipin (CL) and phosphatidylethanolamine (PE) modulate membrane curvature, facilitate membrane fusion and affect the stability and function of membrane proteins. Yeast peroxisomal membranes contain significant amounts of CL and PE. We analysed the effect of CL deficiency and PE depletion on peroxisome biogenesis and proliferation in Saccharomyces cerevisiae. Our data indicate that deletion of CRD1, which encodes cardiolipin synthase, does not affect peroxisome biogenesis or abundance, both at peroxisome repressing (glucose) or inducing (oleate) growth conditions...
October 13, 2016: Biochemical and Biophysical Research Communications
Yan Wang, Min Yu, Yue Ma, Ruo Ping Wang, Wei Liu, Wei Xia, Ai Li Guan, Cong Hui Xing, Fei Lu, Xiao Ping Ji
Peroxisome proliferator-activated receptors alpha (PPARα) is a therapy target in atherosclerosis and cardiovascular diseases. However, anti-inflammatory effects of PPARα in intracerebral hemorrhage (ICH) remain unknown. We investigated the anti-inflammatory effects of fenofibrate, a ligand of PPARα, in ICH rat model. We found that engagement of fenofibrate increased nissl body and astrocytes, and reduced the neuronal damage, which was observed in paraffin section of ICH rat brain. Fenofibrate also promoted the proliferation of astrocytes that were isolated from adult rat brain...
October 14, 2016: Current Neurovascular Research
Dan Ouyang, Lifeng Xu, Lihua Zhang, Dongguang Guo, Xiaotong Tan, Xiaofang Yu, Junjie Qi, Yaqiong Ye, Qihong Liu, Yongjiang Ma, Yugu Li
MicroRNAs are highly conserved non-coding small RNAs participating in almost all kinds of biological activities. MiR-181a has been reported to be involved in the differentiation of porcine primary preadipocytes, but the profound effect of miR-181a-5p on 3T3-L1 adipocyte differentiation and proliferation is still unclear. In this study, we found that supplementation of miR-181a-5p in 3T3-L1 cells significantly promoted the adipogenesis and inhibited cell proliferation with increased expression of adipogenic marker genes including peroxisome proliferator-activated receptor gamma (Pparγ), CCAAT/enhancer-binding protein alpha (C/ebpα), fatty acid-binding protein 4 (Fabp4), and Adiponectin, accompanied by an accumulation of lipid droplet, an increase of triglyceride content, and a decrease of cell proliferation...
October 14, 2016: Acta Biochimica et Biophysica Sinica
Ruobing Xu, Shu Wang, Weishan Li, Zhen Liu, Jiaxin Tang, Xiaobo Tang
OBJECTIVE In this study, the authors investigated the involvement of 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) in the regulation of peroxisome proliferator-activated receptor-γ (PPARγ) after intracerebral hemorrhage (ICH) and its effects on hemorrhage-induced inflammatory response and oxidative stress in an experimental rodent model. METHODS To simulate ICH in a rat model, the authors injected autologous whole blood into the right striatum of male Sprague-Dawley rats. The distribution and expression of 12/15-lipoxygenase (12/15-LOX) were determined by immunohistochemistry and Western blot analysis, respectively...
October 14, 2016: Journal of Neurosurgery
Jonathan C Jun, Ronald Devera, Dileep Unnikrishnan, Mi-Kyung Shin, Shannon Bevans-Fonti, Qiaoling Yao, Aman Rathore, Haris Younas, Nils Halberg, Philipp E Scherer, Vsevolod Y Polotsky
: Hypoxia-inducible factor-1α (HIF-1α) in adipose tissue is known to promote obesity. We hypothesized that HIF-1α interferes with brown fat thermogenesis, thus decreasing energy expenditure. To test this hypothesis, we compared transgenic mice constitutively expressing HIF-1α in adipose tissues (HIF-1α++) at usual temperature (22 °C), where brown fat is somewhat active, or at thermoneutrality (30 °C), where brown fat is minimally active. HIF-1α++ mice or control litter mates were separated into room temperature (22 °C) or thermoneutrality (30 °C) groups...
October 14, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Terry D Hinds, Katherine A Burns, Peter A Hosick, Lucien McBeth, Andrea Nestor-Kalinoski, Heather A Drummond, Adbulhadi A AlAmodi, Michael W Hankins, John P Vanden Heuvel, David E Stec
Non-alcoholic fatty liver disease (NAFLD) is the most rapidly growing form of liver disease, and if left untreated can result in non-alcoholic steatohepatitis (NASH) ultimately resulting in liver cirrhosis and failure. Biliverdin reductase-A (BVRA) is a multi-functioning protein primarily responsible for the reduction of biliverdin to bilirubin. Also, BVRA can function as a kinase and transcription factor, regulating several cellular functions. We report here that liver BVRA protects against hepatic steatosis by inhibiting glycogen synthase kinase-3β (GSK3β) by enhancing serine 9 phosphorylation, which inhibits its activity...
October 10, 2016: Journal of Biological Chemistry
Xijun Liang, Lin Liu, Tingting Fu, Qian Zhou, Danxia Zhou, Liwei Xiao, Jing Liu, Yan Kong, Hui Xie, Fanchao Yi, Ling Lai, Rick B Vega, Daniel P Kelly, Steven R Smith, Zhenji Gan
Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate, which are critical fuel metabolites of skeletal muscle particularly during exercise. However, the physiological relevance of LDH remains poorly understood. Here we show that Ldhb expression is induced by exercise in human muscle and negatively correlated with changes in intramuscular pH levels, a marker of lactate production, during isometric exercise. We found that the expression of Ldhb is regulated by exercise-induced peroxisome proliferator-activated receptor-g coactivator 1α (PGC-1α)...
October 13, 2016: Journal of Biological Chemistry
Yoo Kim, Daeyoung Kim, Yeonhwa Park
Previously, it was reported that conjugated linoleic acid (CLA) with exercise training potentially improved endurance capacity via the peroxisome proliferator-activated receptor δ (PPARδ)-mediated mechanism in mice. This study determined the role of exercise and/or CLA in endurance capacity and PPARδ-associated regulators. Male 129Sv/J mice were fed either control (soybean oil) or CLA (0.5%) containing diets for 4 weeks and were further divided into sedentary or training regimes. CLA supplementation significantly reduced body weight and fat mass independent of exercise during the experimental period...
September 7, 2016: Journal of Nutritional Biochemistry
Chao-Wei Huang, Yi-Shan Chien, Yu-Jen Chen, Kolapo M Ajuwon, Harry M Mersmann, Shih-Torng Ding
The incidence of obesity and its comorbidities, such as insulin resistance and type II diabetes, are increasing dramatically, perhaps caused by the change in the fatty acid composition of common human diets. Adipose tissue plays a role as the major energy reservoir in the body. An excess of adipose mass accumulation caused by chronic positive energy balance results in obesity. The n-3 polyunsaturated fatty acids (n-3 PUFA), DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) exert numerous beneficial effects to maintain physiological homeostasis...
October 9, 2016: International Journal of Molecular Sciences
Ashraf S Gorgey, Zachary A Graham, William A Bauman, Christopher Cardozo, David R Gater
STUDY DESIGN: Longitudinal design. OBJECTIVES: The study determined the effects of two forms of exercise training on the abundance of two proteins, (glucose transporter-4 [GLUT-4], adenosine monophosphate kinase [AMPK]) involved in glucose utilization and the transcriptional coactivator that regulates the genes involved in energy metabolism and mitochondrial biogenesis (peroxisome proliferator-activated receptor (PPAR) coactivator 1 alpha [PGC-1α]), in muscles in men with chronic motor-complete spinal cord injury (SCI)...
October 13, 2016: Journal of Spinal Cord Medicine
Y Li, C G Zhang, X-H Wang, D-H Liu
OBJECTIVE: To construct the atherosclerosis model of ApoE-knockout (ApoE-/-) mouse after deposition of high-fat diet at brachiocephalic artery and coronary artery. MATERIALS AND METHODS: 40 healthy 8-week SPF-level male ApoE-/- mice of body weigh 16 to 23 g were averagely divided into a high-fat diet group and an ordinary diet group. Mice were sacrificed in a time course study by 3 months, 6 months, 9 months and 12 months. The brachiocephalic artery and coronary artery were extracted for pathological examination, and enzyme-linked immunosorbent assay (ELISA) was used for the examination of serum high-sensitivity C-reactive protein (hs-CRP) content and the relative expression level of liver peroxisome proliferator activated receptor (PPAR)...
September 2016: European Review for Medical and Pharmacological Sciences
Christoph Tondera, Markus Laube, Jens Pietzsch
The EF-hand type calcium-binding protein S100A12 exerts numerous intra- and extracellular functions of (patho)physiological relevance. Therefore, receptors of S100A12 are of high interest for research and clinical applications. Beside the extensively studied receptor for advanced glycation endproducts (RAGE), G-protein coupled receptors and more recently, scavenger receptors are suggested to be putative S100A12 receptors. Own findings and further information from the literature predestined CD36, a class B scavenger receptor, as promising candidate...
October 12, 2016: Amino Acids
Ramon Gonzalez, Pilar Morales, Jordi Tronchoni, Gustavo Cordero-Bueso, Enrico Vaudano, Manuel Quirós, Maite Novo, Rafael Torres-Pérez, Eva Valero
Adaptation to changes in osmolarity is fundamental for the survival of living cells, and has implications in food and industrial biotechnology. It has been extensively studied in the yeast Saccharomyces cerevisiae, where the Hog1 stress activated protein kinase was discovered about 20 years ago. Hog1 is the core of the intracellular signaling pathway that governs the adaptive response to osmotic stress in this species. The main endpoint of this program is synthesis and intracellular retention of glycerol, as a compatible osmolyte...
2016: Frontiers in Microbiology
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