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Liliana F Iannucci, Jingfeng Sun, Brijesh K Singh, Jin Zhou, Vincent A Kaddai, Antonia Lanni, Paul M Yen, Rohit A Sinha
Short-chain fatty acids (SCFAs) are gut microbial fermentation products derived from dietary fiber sources. Although depletion of gut microflora has been linked to the development of liver disease, the direct effects of SCFAs on intracellular hepatic processes are not well understood. In this study, we demonstrated that the SCFAs, propionate and butyrate, regulated autophagic flux in hepatic cells in a cell-autonomous manner. Induction of autophagy by SCFAs required PPARγ stimulation of Uncoupling Protein 2 (UCP2) expression that was associated with reduced intracellular ATP levels and activation of PRKAA1/AMPK (protein kinase, AMP-activated, alpha 1 catalytic subunit)...
October 20, 2016: Biochemical and Biophysical Research Communications
C Cortes-Oliveira, C F Nicoletti, M A de Souza Pinhel, B A P de Oliveira, D C G Quinhoneiro, N Y Noronha, J S Marchini, W A da Silva Júnior, W S Júnior, C B Nonino
BACKGROUND/OBJECTIVES: Although energy restriction contributes to weight loss, it may also reduce energy expenditure, limiting the success of weight loss in the long term. Studies have described how genetics contributes to the development of obesity, and uncoupling proteins 1 and 2 (UCP1 and UCP2) and beta-3-adrenoceptor (ADRB3) have been implicated in the metabolic pathways that culminate in this condition. This study aimed to evaluate how the UCP1, UCP2 and ADRB3 genes influence weight loss in severely obese women submitted to hypocaloric dietary intervention...
October 19, 2016: European Journal of Clinical Nutrition
Carolina F Nicoletti, Ana Paula R P de Oliveira, Maria José F Brochado, Marcela A S Pinhel, Bruno A P de Oliveira, Julio S Marchini, José E Dos Santos, Wilson Salgado, Nathalia Moreno Cury, Luiza Ferreira de Araújo, Wilson A Silva, Carla B Nonino
OBJECTIVE: The aim of this study was to investigate whether the Ala55Val and -866G>A polymorphisms of the UCP2 gene are related to weight loss and changes in body composition after bariatric surgery performed by Roux-en-Y gastric bypass (RYGB). METHODS: This longitudinal study enrolled obese patients submitted to RYGB. Data regarding weight (kg), body mass index (kg/m(2)), fat-free mass (FFM; kg), fat mass (kg), weight loss (kg and %), and percent excess weight loss were collected from both preoperative and 1-y postoperative medical records...
August 9, 2016: Nutrition
Shantaé M Thornton, James E Krolopp, Marcia J Abbott
Molecular mediators of metabolic processes, to increase energy expenditure, have become a focus for therapies of obesity. The discovery of cytokines secreted from the skeletal muscle (SKM), termed "myokines," has garnered attention due to their positive effects on metabolic processes. Interleukin-15 (IL-15) is a myokine that has numerous positive metabolic effects and is linked to the PPAR family of mitochondrial regulators. Here, we aimed to determine the importance of PPARα and/or PPARδ as targets of IL-15 signaling...
2016: PPAR Research
Shuvasree Sarkar, Sandip Mukherjee, Ansuman Chattopadhyay, Shelley Bhattacharya
Zebrafish were exposed to a nonlethal dose (1/350LC50; 50µg/L) of As2O3 and sampled at 7, 15, 30, 60 and 90 days of treatment. The oxidative stress response was assessed in terms of time-dependent histopathological changes, lipid peroxidation, GSH status, activities of detoxification enzymes and expression of antioxidant genes in liver and kidney. As2O3 treatment enhanced lipid peroxidation except at day 90 in liver and day 30 in kidney. Glutathione depleted significantly in the liver except on day 30; whereas in kidney, it increased initially but thereafter depleted significantly...
October 10, 2016: Ecotoxicology and Environmental Safety
Luisa Pozzo, Andrea Vornoli, Ilaria Coppola, Clara Maria Della Croce, Lucia Giorgetti, Pier Giovanni Gervasi, Vincenzo Longo
AIMS: The aim of the study was to evaluate lipid, cholesterol and glucose metabolism in a novel rat model of non-alcoholic fatty liver disease (NAFLD). MAIN METHODS: Rats (Wistar) were fed high fat/cholesterol diet (HFD) and a single low dose (35mg/kg) of streptozotocin (STZ). Collagen and glycogen content, oxidative stress and glucokinase activity were measured using biochemical assays. Other metabolic pathway were assessed by qRT-PCR. KEY FINDINGS: HFD/STZ treated rats, compared to control ones, showed an increase in expression of biomarkers of inflammation (TNFα, IL6), fibrosis (TGFβ), mitochondrial stress (UCP2) and oxidative stress (GSH and carbonylated proteins) but not of ER stress (CHOP, XBP1)...
September 28, 2016: Life Sciences
Xi Jin, Chun-Yan Feng, Zun Xiang, Yi-Peng Chen, You-Ming Li
The pathogenesis of nonalcoholic steatohepatitis (NASH) is still unclear, where involvement of circRNA is considered for its active role as "miRNA sponge". Therefore, we aimed to investigate the circRNA expression pattern in NASH and further construct the circRNA-miRNA-mRNA network for in-depth mechanism exploration. Briefly, NASH mice model was established by Methionine and choline deficiency (MCD) diet feeding. Liver circRNA and mRNA profile was initially screened by microarray and ensuing qRT-PCR verification was carried out...
September 22, 2016: Oncotarget
Thomas W Bastian, William C von Hohenberg, Daniel J Mickelson, Lorene M Lanier, Michael K Georgieff
Iron deficiency (ID), with and without anemia, affects an estimated 2 billion people worldwide. ID is particularly deleterious during early-life brain development, leading to long-term neurological impairments including deficits in hippocampus-mediated learning and memory. Neonatal rats with fetal/neonatal ID anemia (IDA) have shorter hippocampal CA1 apical dendrites with disorganized branching. ID-induced dendritic structural abnormalities persist into adulthood despite normalization of the iron status. However, the specific developmental effects of neuronal iron loss on hippocampal neuron dendrite growth and branching are unknown...
September 27, 2016: Developmental Neuroscience
Daniel T Hass, Colin J Barnstable
Reactive oxygen species (ROS) are free radicals thought to mediate the neurotoxic effects of several neurodegenerative disorders. In the central nervous system, ROS can also trigger a phenotypic switch in both astrocytes and microglia that further aggravates neurodegeneration, termed reactive gliosis. Negative regulators of ROS, such as mitochondrial uncoupling protein 2 (UCP2) are neuroprotective factors that decrease neuron loss in models of stroke, epilepsy, and parkinsonism. However, it is unclear whether UCP2 acts purely to prevent ROS production, or also to prevent gliosis...
August 2016: Neural Regeneration Research
Bruno G Teodoro, Igor H Sampaio, Lucas H M Bomfim, André L Queiroz, Leonardo R Silveira, Anderson O Souza, Anna M A P Fernandes, Marcos N Eberlin, Tai-Yu Huang, Donghai Zheng, P Darrell Neufer, Ronald N Cortright, Luciane C Alberici
Long-chain Acyl-CoA Synthetases (ACSL 1 to 6) are key enzymes regulating partitioning of acyl-CoA species toward different metabolic fates such as lipid synthesis or β-oxidation. Despite the understanding that ecotopic lipid accumulation in skeletal muscle is associated with metabolic diseases like obesity and Type II Diabetes, the role of specific ACSL isoforms in lipid synthesis remains unclear. Herein we describe for the first time the presence of ACSL6 mRNA in human skeletal muscle and the role that ACSL6 plays in lipid synthesis in both rodent and human skeletal muscle...
September 20, 2016: Journal of Physiology
Angélica Ruiz-Ramírez, Ocarol López-Acosta, Miguel Angel Barrios-Maya, Mohammed El-Hafidi
Metabolic diseases such as obesity, metabolic syndrome, and type II diabetes are often characterized by increased reactive oxygen species (ROS) generation in mitochondrial respiratory complexes, associated with fat accumulation in cardiomyocytes, skeletal muscle, and hepatocytes. Several rodents studies showed that lipid accumulation in cardiac myocytes produces lipotoxicity that causes apoptosis and leads to heart failure, a dynamic pathological process. Meanwhile, several tissues including cardiac tissue develop an adaptive mechanism against oxidative stress and lipotoxicity by overexpressing uncoupling proteins (UCPs), specific mitochondrial membrane proteins...
2016: Oxidative Medicine and Cellular Longevity
Corina T Madreiter-Sokolowski, Christiane Klec, Warisara Parichatikanond, Sarah Stryeck, Benjamin Gottschalk, Sergio Pulido, Rene Rost, Emrah Eroglu, Nicole A Hofmann, Alexander I Bondarenko, Tobias Madl, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F Graier
Recent studies revealed that mitochondrial Ca(2+) channels, which control energy flow, cell signalling and death, are macromolecular complexes that basically consist of the pore-forming mitochondrial Ca(2+) uniporter (MCU) protein, the essential MCU regulator (EMRE), and the mitochondrial Ca(2+) uptake 1 (MICU1). MICU1 is a regulatory subunit that shields mitochondria from Ca(2+) overload. Before the identification of these core elements, the novel uncoupling proteins 2 and 3 (UCP2/3) have been shown to be fundamental for mitochondrial Ca(2+) uptake...
September 19, 2016: Nature Communications
Yuling Zhou, David Simmons, Brett D Hambly, Craig S McLachlan
Mitochondrial uncoupling protein 2 (UCP2) can affect oxidative stress levels. UCP2 polymorphisms are associated with leukocyte telomere length (LTL) in Type 2 Diabetes, which also induces considerable background oxidative stress. The effects of UCP2 polymorphisms on LTL in populations without diabetes have not been well described. Our aims are to evaluate the interaction between LTL and UCP2 polymorphisms in 950 subjects without diabetes. The monochrome multiplex quantitative PCR method was used to measure relative LTL...
2016: Scientific Reports
Speranza Rubattu, Rosita Stanzione, Massimo Volpe
Mechanisms underlying hypertensive target organ damage (TOD) are not completely understood. The pathophysiological role of mitochondrial oxidative stress, resulting from mitochondrial dysfunction, in development of TOD is unclear. The stroke-prone spontaneously hypertensive rat (SHRSP) is a suitable model of human hypertension and of its vascular consequences. Pathogenesis of TOD in SHRSP is multifactorial, being determined by high blood pressure levels, high salt/low potassium diet, and genetic factors. Accumulating evidence points to a key role of mitochondrial dysfunction in increased susceptibility to TOD development of SHRSP...
2016: Oxidative Medicine and Cellular Longevity
Ren-Hong Du, Fang-Fang Wu, Ming Lu, Xiao-Dong Shu, Jian-Hua Ding, Guangyu Wu, Gang Hu
Mitochondrial uncoupling protein 2 (UCP2) has been well characterized to control the production of reactive oxygen species (ROS) and astrocytes are the major cells responsible for the ROS production and the inflammatory responses in the brain. However, the function of UCP2 in astrocytes and the contribution of astrocytic UCP2 to depression remain undefined. Herein, we demonstrated that UCP2 knockout (KO) mice displayed aggravated depressive-like behaviors, impaired neurogenesis, and enhanced loss of astrocytes in the chronic mild stress (CMS)-induced anhedonia model of depression...
August 18, 2016: Redox Biology
Shafat Ali, Shazia Nafis, Ponnusamy Kalaiarasan, Ekta Rai, Swarkar Sharma, Rameshwar N Bamezai
Type 2 diabetes (T2D) is a chronic metabolic disease which shows an exponential increase in all parts of the world. However, the disease is controllable by early detection and modified lifestyle. A series of factors have been associated with the pathogenesis of diabetes, and genes are considered to play a critical role. The individual risk of developing T2D is determined by an altered genetic background of the en-zymes involved in several metabolism-related biological mechanisms, including glucose homeostasis, insulin metab-olism, the glucose and ion transporters involved in glucose uptake, transcription factors, signaling intermediates of insulin signaling pathways, insulin production and secretion, pancreatic tissue development, and apoptosis...
2016: Review of Diabetic Studies: RDS
Santoshi Kumari Manche, Madhavi Jangala, Padmavathi Putta, Raja Meganadh Koralla, Jyothy Akka
INTRODUCTION: Presbycusis is characterised by etiopathological changes in the cochlea of the inner ear due to genetic and environmental factors and has a serious impact on quality of life. The present study was aimed to evaluate the role of oxidant stress gene polymorphisms in the development of presbycusis. SUBJECTS AND METHODS: 220 subjects with confirmed presbycusis from ENT specialists of MAA ENT hospital, Hyderabad, India from 2012 to 2014 were considered for the study...
November 30, 2016: Gene
J Y Diao, J Wei, R Yan, L Lin, H Li
OBJECTIVE: To observe the expression of uncoupling protein (UCP2) and its effect on modulation of mitochondrial function and apoptosis of cardiomyocytes exposed to high-glucose. METHODS: AC16 cardiomyoctyes were randomly divided into normal-glucose group (NG), high-glucose group (HG), HG+ UCP2 siRNA group and HG+ negative control siRNA group.The expression of UCP2, succinodehydrogenase(SDH) activity, ATP content, reactive oxygen species (ROS) generation, cell apoptotic rate, caspase-3 activity and cell viability were detected...
August 16, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Aneta A Koronowicz, Paula Banks, Dominik Domagała, Adam Master, Teresa Leszczyńska, Ewelina Piasna, Mariola Marynowska, Piotr Laidler
BACKGROUND: Our previous study showed that fatty acids extract obtained from CLA-enriched egg yolks (EFA-CLA) suppressed the viability of MCF-7 cancer cell line more effectively than extract from non-enriched egg yolks (EFA). In this study, we analysed the effect of EFA-CLA and EFA on transcriptome profile of MCF-7 cells by applying the whole Human Genome Microarray technology. RESULTS: We found that EFA-CLA and EFA treated cells differentially regulated genes involved in cancer development and progression...
2016: Genes & Nutrition
Christin Kretzschmar, Catrin Roolf, Katrin Timmer, Anett Sekora, Gudrun Knübel, Hugo Murua Escobar, Robert Jaster, Sarah Müller, Georg Fuellen, Rüdiger Köhling, Christian Junghanss
Progress of age-related hematopoietic diseases such as myelodysplastic syndrome has previously been linked to enhanced levels of reactive oxygen species (ROS). Uncoupling protein 2 (UCP2) was found to reduce mitochondrial ROS production through uncoupling of the respiratory chain. The impact of UCP2 loss and elevated ROS on hematopoiesis during aging has not yet been investigated. In this study, UCP2 knockout mice were analyzed at aging stages of 3, 12, and 24 months with respect to oxidative and energy status of bone marrow cells...
August 17, 2016: Experimental Hematology
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