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Georgina Gyetvai, Trisha Hughes, Florence Wedmore, Cieron Roe, Lamia Heikal, Pietro Ghezzi, Manuela Mengozzi
Several studies have shown that erythropoietin (EPO) has neuroprotective or neuroreparative actions on diseases of the nervous system and that improves oligodendrocyte (OL) differentiation and myelination in vivo and in vitro . This study aims at investigating the early molecular mechanisms for the pro-myelinating action of EPO at the gene expression level. For this purpose, we used a differentiating OL precursor cell line, rat central glia-4 cells. Cells were differentiated or not, and then treated with EPO for 1 or 20 h...
2017: Frontiers in Immunology
Jay W Porter, Joe L Rowles, Justin A Fletcher, Terese M Zidon, Nathan C Winn, Leighton T McCabe, Young-Min Park, James W Perfield, John P Thyfault, R Scott Rector, Jaume Padilla, Victoria J Vieira-Potter
Exercise enhances insulin sensitivity; it also improves adipocyte metabolism and reduces adipose tissue inflammation through poorly defined mechanisms. Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone-like protein whose insulin-sensitizing properties are predominantly mediated via receptor signaling in adipose tissue (AT). Recently, FGF21 has also been demonstrated to have anti-inflammatory properties. Meanwhile, an association between exercise and increased circulating FGF21 levels has been reported in some, but not all studies...
November 2017: Journal of Endocrinology
Sharon J Manley, Wen Liu, Danny R Welch
The shift by cancer cells toward aerobic glycolysis (Warburg effect) confers selective advantages by utilizing nutrients (e.g., lipids, amino acids, and nucleotides) to build biomass. Lipogenesis is generally enhanced, and its inhibition diminishes proliferation and survival. Re-expression of the metastasis suppressor KISS1 in human melanoma cells results in greater mitochondrial biogenesis, inhibition of glycolysis, utilization of beta-oxidation to provide energy, elevated oxidation of exogenous fatty acids, and increased expression of early-phase lipogenesis genes at both mRNA and protein levels...
September 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Fumihito Noguchi, Shigeki Inui, Clare Fedele, Mark Shackleton, Satoshi Itami
Extracellular acidity is a hallmark of cancers and is independent of hypoxia. Because acidity potentiates malignant phenotypes, therapeutic strategies that enhance the targeting of oncogenic mechanisms in an acidic microenvironment should be effective. We report here that drugs which abrogate mitochondrial respiration show enhanced cytotoxicity against melanoma cells in a normoxic but acidic extracellular pH, independent from P53 mutations, BRAF (V600E) mutations, and/or resistance against BRAF inhibitors. Conversely, the cytotoxicity against melanoma cells of mitochondrial inhibitors is impaired by a neutral or alkaline extracellular pH, and in vivo systemic alkalinization with NaHCO3 enhanced subcutaneous tumor growth and lung metastasis of B16F10 cells in mice treated with the mitochondrial inhibitor phenformin...
May 2017: Molecular Cancer Therapeutics
Fabiane Ferreira Martins, Thereza Cristina Lonzetti Bargut, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
Brown adipose tissue (BAT) is specialized in heat production, but its metabolism in ob/ob mice is still a matter of debate. We aimed to verify ob/ob mice BAT using C57Bl/6 male mice (as the wild-type, WT) and leptin-deficient ob/ob mice (on the C57Bl/6 background strain), at three months of age (n=10/group). At euthanasia, animals had their interscapular BAT weighed, and prepared for analysis (Western blot, and RT-qPCR). In comparison with the WT group, the ob/ob group showed reduced thermogenic signaling markers (gene expression of beta 3-adrenergic receptor, beta3-AR; PPARgamma coactivator 1 alpha, PGC1alpha, and uncoupling protein 1, UCP1)...
March 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Anne Drougard, Audren Fournel, Alysson Marlin, Etienne Meunier, Anne Abot, Tereza Bautzova, Thibaut Duparc, Katie Louche, Aurelie Batut, Alexandre Lucas, Sophie Le-Gonidec, Jean Lesage, Xavier Fioramonti, Cedric Moro, Philippe Valet, Patrice D Cani, Claude Knauf
Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions...
August 23, 2016: Scientific Reports
Almas Siddiqui, Anand Rane, Subramanian Rajagopalan, Shankar J Chinta, Julie K Andersen
Loss of parkin E3 ligase activity as a result of parkin gene mutation in rare familial forms of Parkinson's disease (PD) has been shown to be detrimental to mitochondrial function and to contribute to ensuing neurodegeneration. This has been shown by ourselves and others to be in part due to reductions in parkin-mediated ubiquitination of the transcriptional repressor PARIS, limiting the protein's subsequent degradation by the proteasome. Subsequent elevations in PARIS protein levels result in reduced expression of the master mitochondrial regulator PGC-1α, impacting in turn on mitochondrial function...
September 2016: Neurobiology of Disease
Georg Auburger, Suzana Gispert, Nadine Brehm
Hereditary Parkinson's disease can be triggered by an autosomal dominant overdose of alpha-Synuclein (SNCA) or the autosomal recessive deficiency of PINK1. We recently showed that the combination of PINK1-knockout with overexpression of A53T-SNCA in double mutant (DM) mice potentiates phenotypes and reduces survival. Now we studied brain hemispheres of DM mice at age of 18 months in a hypothesis-free approach, employing a quantitative label-free global proteomic mass spectrometry scan of posttranslational modifications focusing on methyl-arginine...
2016: Parkinson's Disease
Thereza Cristina Lonzetti Bargut, Vanessa Souza-Mello, Carlos Alberto Mandarim-de-Lacerda, Marcia Barbosa Aguila
We aimed to investigate the impact of different high-fat diets containing fish oil on adiposity and white adipose tissue (WAT) function in mice, comparing the effects on epididymal (eWAT) and subcutaneous (sWAT) depots. For this, we used C57BL/6 male mice fed four types of diets for eight weeks: standard chow (SC), high-fat lard (HF-L), high-fat lard plus fish oil (HF-L + FO), and high-fat fish oil (HF-FO). The HF-L group had a greater body mass (BM) gain, insulin resistance, increased gene expression related to lipogenesis (CD36, aP2, SREBP1c, and FAS), decreased gene expression of perilipin in both eWAT and sWAT, and reduced expression of genes related to beta-oxidation (CPT-1a) and to mitochondrial biogenesis (PGC1alpha, NRF1, and TFAM) in eWAT and sWAT...
March 2016: Food & Function
Tetsuya Hosooka, Wataru Ogawa
Dysregulation of gluconeogenesis is a key pathological feature of type 2 diabetes. However, the molecular mechanisms underlying the regulation of gluconeogenesis remain unclear. Bhalla et al. recently reported that cyclin D1 suppresses hepatic gluconeogenesis through CDK4-dependent phosphorylation of PGC1alpha and consequent inhibition of its activity. The cyclin D1-CDK4 might thus serve as an important link between the cell cycle and control of energy metabolism through modulation of PGC1alpha activity.
January 2016: Journal of Diabetes Investigation
Stephanie Hagl, Dirk Berressem, Rehka Grewal, Nadine Sus, Jan Frank, Gunter P Eckert
OBJECTIVES: Aging represents a major risk factor for neurodegenerative diseases such as Alzheimer's disease. Mitochondria are significantly involved in both the aging process and neurodegeneration. One strategy to protect the brain and to prevent neurodegeneration is a healthy lifestyle including a diet rich in antioxidants and polyphenols. Rice bran extract (RBE) contains various antioxidants including natural vitamin E forms (tocopherols and tocotrienols) and gamma-oryzanol. In this work, we examined the effects of a stabilized RBE on mitochondrial function in 18-month-old Naval Medical Research Institute mice (340 mg/kg body weight/day), which received the extract for 3 weeks via oral gavage...
2016: Nutritional Neuroscience
Thereza Cristina Lonzetti Bargut, Anna Carolina Alves Gomes Silva-e-Silva, Vanessa Souza-Mello, Carlos Alberto Mandarim-de-Lacerda, Marcia Barbosa Aguila
PURPOSE: Fish oil (FO) elicits diverse beneficial effects. Reduction in or prevention of body mass (BM) gain in animal models may be associated with modulation of brown adipose tissue (BAT). We aimed to evaluate the effects of different high-fat diets with FO on BAT metabolism and thermogenic markers. METHODS: C57BL/6 male mice (3-month-old) were fed different diets during 8 weeks: standard-chow diet (SC 10% fat), high-fat lard diet (HF-L 50% fat), high-fat lard plus FO diet (HF-L+FO 50% fat), and high-fat FO diet (HF-FO 50% fat)...
February 2016: European Journal of Nutrition
Tamiris Lima Rachid, Aline Penna-de-Carvalho, Isabele Bringhenti, Marcia B Aguila, Carlos A Mandarim-de-Lacerda, Vanessa Souza-Mello
Browning is characterized by the formation of beige/brite fat depots in subcutaneous white adipose tissue (sWAT). This study aimed to examine whether the chronic activation of PPARalpha by fenofibrate could induce beige cell depots in the sWAT of diet-induced obese mice. High-fat fed animals presented overweight, insulin resistance and displayed adverse sWAT remodeling. Fenofibrate significantly attenuated these parameters. Treated groups demonstrated active UCP-1 beige cell clusters within sWAT, confirmed through higher gene expression of PPARalpha, PPARbeta, PGC1alpha, BMP8B, UCP-1, PRDM16 and irisin in treated groups...
February 15, 2015: Molecular and Cellular Endocrinology
Sebastian Höppner, Wilhelm Schänzer, Mario Thevis
RATIONALE: The efficiency of Sirtuin1, a major target for the treatment of various metabolic disorders such as inflammation and type 2 diabetes mellitus, can be modulated via low molecular mass SIRT1 activators (e.g. resveratrol, SRT1720, and SRT2104).The administration of such compounds results in increased deacetylation of substrates including p53, FOXO1, and PGC1alpha, potentially leading to an improved physical performance. Consequently, proactive and preventive anti-doping measures are required and an assay dedicated to serum and plasma was desirable...
January 15, 2013: Rapid Communications in Mass Spectrometry: RCM
Almas Siddiqui, Shankar J Chinta, Jyothi K Mallajosyula, Subramanian Rajagopolan, Ingrid Hanson, Anand Rane, Simon Melov, Julie K Andersen
Alpha-synuclein has been reported to be present in the nucleus and levels enhanced by oxidative stress. Herein, we sought to investigate the mechanistic role of nuclear alpha-synuclein. We found that alpha-synuclein nuclear localization coincided with enhanced chromatin binding both in an in vitro and a corresponding in vivo brain oxidative stress model previously characterized by our laboratory as well as in PD brain tissues. Genome-wide chromatin immunoprecipitation (ChIP)-on-chip analysis of alpha-synuclein:promoter binding in response to oxidative stress in vitro revealed that binding occurs at several promoters belonging to a range of functional categories including transcriptional regulation...
August 15, 2012: Free Radical Biology & Medicine
Ruojing Yang, Raul G Lacson, Gino Castriota, Xiaohua D Zhang, Yaping Liu, Wenqing Zhao, Monica Einstein, Luiz Miguel Camargo, Sajjad Qureshi, Kenny K Wong, Bei B Zhang, Marc Ferrer, Joel P Berger
BACKGROUND: Hepatic insulin resistance impairs insulin's ability to suppress hepatic glucose production (HGP) and contributes to the development of type 2 diabetes (T2D). Although the interests to discover novel genes that modulate insulin sensitivity and HGP are high, it remains challenging to have a human cell based system to identify novel genes. METHODOLOGY/PRINCIPAL FINDINGS: To identify genes that modulate hepatic insulin signaling and HGP, we generated a human cell line stably expressing beta-lactamase under the control of the human glucose-6-phosphatase (G6PC) promoter (AH-G6PC cells)...
2012: PloS One
Ilenia D'Errico, Lorena Salvatore, Stefania Murzilli, Giuseppe Lo Sasso, Dominga Latorre, Nicola Martelli, Anastasia V Egorova, Roman Polishuck, Katja Madeyski-Bengtson, Christopher Lelliott, Antonio J Vidal-Puig, Peter Seibel, Gaetano Villani, Antonio Moschetta
Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is a transcriptional coactivator able to up-regulate mitochondrial biogenesis, respiratory capacity, oxidative phosphorylation, and fatty acid β-oxidation with the final aim of providing a more efficient pathway for aerobic energy production. In the continuously renewed intestinal epithelium, proliferative cells in the crypts migrate along the villus axis and differentiate into mature enterocytes, increasing their respiratory capacity and finally undergoing apoptosis...
April 19, 2011: Proceedings of the National Academy of Sciences of the United States of America
Denis Richard, Frederic Picard
Brown fat (brown adipose tissue, BAT) primary function is to produce heat. There is now compelling evidence to indicate that brown fat cells in some BAT depots share their predecessor cells with myocytes. Brown adipocyte (trans)differentiation depends on various receptors / transcription factors that include peroxisome proliferator-activated receptor g (PPARgamma), PPARgamma-coactivator-1alpha (PGC1alpha), PRD1-BF1-RIZ1 homologous domain-containing 16 (PRDM16), CCAAT/enhancer-binding protein beta (C/EBP-beta) and bone morphogenetic protein 7 (BMP7)...
January 1, 2011: Frontiers in Bioscience (Landmark Edition)
Jonathan Goldwasser, Pazit Y Cohen, Eric Yang, Patrick Balaguer, Martin L Yarmush, Yaakov Nahmias
Disruption of lipid and carbohydrate homeostasis is an important factor in the development of prevalent metabolic diseases such as diabetes, obesity, and atherosclerosis. Therefore, small molecules that could reduce insulin dependence and regulate dyslipidemia could have a dramatic effect on public health. The grapefruit flavonoid naringenin has been shown to normalize lipids in diabetes and hypercholesterolemia, as well as inhibit the production of HCV. Here, we demonstrate that naringenin regulates the activity of nuclear receptors PPARalpha, PPARgamma, and LXRalpha...
August 25, 2010: PloS One
Bingfang Zhang, Subat Turdi, Quan Li, Faye L Lopez, Anna R Eason, Piero Anversa, Jun Ren
Chronic alcohol intake leads to the development of alcoholic cardiomyopathy manifested by cardiac hypertrophy and contractile dysfunction. This study was designed to examine the effects of transgenic overexpression of insulin-like growth factor 1 (IGF-1) on alcohol-induced cardiac contractile dysfunction. Wild-type FVB and cardiac-specific IGF-1 mice were placed on a 4% alcohol or control diet for 16weeks. Cardiac geometry and mechanical function were evaluated by echocardiography and cardiomyocyte and intracellular Ca(2+) properties...
October 15, 2010: Free Radical Biology & Medicine
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