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HDAC obesity

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https://www.readbyqxmd.com/read/27906092/alterations-to-mtorc1-signaling-in-the-skeletal-muscle-differentially-affect-whole-body-metabolism
#1
Maitea Guridi, Barbara Kupr, Klaas Romanino, Shuo Lin, Denis Falcetta, Lionel Tintignac, Markus A Rüegg
BACKGROUND: The mammalian target of rapamycin complex 1 (mTORC1) is a central node in a network of signaling pathways controlling cell growth and survival. This multiprotein complex integrates external signals and affects different nutrient pathways in various organs. However, it is not clear how alterations of mTORC1 signaling in skeletal muscle affect whole-body metabolism. RESULTS: We characterized the metabolic phenotype of young and old raptor muscle knock-out (RAmKO) and TSC1 muscle knock-out (TSCmKO) mice, where mTORC1 activity in skeletal muscle is inhibited or constitutively activated, respectively...
March 21, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27900262/impaired-histone-deacetylases-5-and-6-expression-mimics-the-effects-of-obesity-and-hypoxia-on-adipocyte-function
#2
Julien Bricambert, Dimitri Favre, Saška Brajkovic, Amélie Bonnefond, Raphael Boutry, Roberto Salvi, Valérie Plaisance, Mohamed Chikri, Giulia Chinetti-Gbaguidi, Bart Staels, Vittorio Giusti, Robert Caiazzo, François Pattou, Gérard Waeber, Philippe Froguel, Amar Abderrahmani
OBJECTIVE: The goal of the study was to investigate the role of histone deacetylases (HDACs) in adipocyte function associated with obesity and hypoxia. METHODS: Total proteins and RNA were prepared from human visceral adipose tissues (VAT) of human obese and normal weight subjects and from white adipose tissue (WAT) of C57Bl6-Rj mice fed a normal or high fat diet (HFD) for 16 weeks. HDAC activity was measured by colorimetric assay whereas the gene and protein expression were monitored by real-time PCR and by western blotting, respectively...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27795551/attenuation-of-diet-induced-obesity-and-induction-of-white-fat-browning-with-a-chemical-inhibitor-of-histone-deacetylases
#3
A Ferrari, E Fiorino, R Longo, S Barilla, N Mitro, G Cermenati, M Giudici, D Caruso, A Mai, U Guerrini, E De Fabiani, M Crestani
BACKGROUND/OBJECTIVES: In the last decade a strict link between epigenetics and metabolism has been demonstrated. Histone deacetylases (HDACs) have emerged as key epigenetic regulators involved in metabolic homeostasis in normal and pathologic conditions. Here we investigated the effect of the class I HDAC inhibitor MS-275 in a model of obesity induced by a high fat diet (HFD). METHODS: C57BL6/J male mice were fed HFD for 17 weeks and then randomized in two groups treated intraperitoneally with vehicle (DMSO) or with the class I selective HDAC inhibitor MS-275 every other day for 22 days...
October 31, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27620069/histone-deacetylase-inhibitors-future-therapeutics-for-insulin-resistance-and-type-2-diabetes
#4
Sorabh Sharma, Rajeev Taliyan
Insulin resistance is a common feature of obesity and predisposes the affected individuals to a variety of pathologies, including type 2 diabetes mellitus (T2DM), dyslipidemias, hypertension, cardiovascular disease etc. Insulin resistance is the primary cause of T2DM and it occurs many years before the disease onset. Although Thiazolidinediones (TZDs) such as rosiglitazone and pioglitazone are outstanding insulin sensitizers and are in clinical use since 1990s, however, their serious side effects such as heart attack and bladder cancer have limited their utilization...
September 9, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27614433/hdac5-inhibits-hepatic-lipogenic-genes-expression-by-attenuating-the-transcriptional-activity-of-liver-x-receptor
#5
Hai-Yan Jia, Quan-Zhong Li, Li-Fang Lv
BACKGROUND/AIMS: Liver X receptor (LXR), a member of the nuclear receptor superfamily, is known to induce the expression of SREBP-1c and ChREBP, two master regulators of hepatic lipogenesis. Histone deacyetylases (HDACs) have been shown to play critical roles in glucose and lipids metabolism. However, the exact role of HDAC5 in lipogenesis remains elusive. METHODS: mRNA and protein levels of HDAC5 were analyzed by quantitative real-time PCR and Western blots in high-fat-diet-induced and leptin receptor deficiency-induced obese mice...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27346602/the-neuropharmacology-of-butyrate-the-bread-and-butter-of-the-microbiota-gut-brain-axis
#6
REVIEW
Roman M Stilling, Marcel van de Wouw, Gerard Clarke, Catherine Stanton, Timothy G Dinan, John F Cryan
Several lines of evidence suggest that brain function and behaviour are influenced by microbial metabolites. Key products of the microbiota are short-chain fatty acids (SCFAs), including butyric acid. Butyrate is a functionally versatile molecule that is produced in the mammalian gut by fermentation of dietary fibre and is enriched in butter and other dairy products. Butyrate along with other fermentation-derived SCFAs (e.g. acetate, propionate) and the structurally related ketone bodies (e.g. acetoacetate and d-β-hydroxybutyrate) show promising effects in various diseases including obesity, diabetes, inflammatory (bowel) diseases, and colorectal cancer as well as neurological disorders...
October 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27164441/benzyl-butyl-phthalate-induces-epigenetic-stress-to-enhance-adipogenesis-in-mesenchymal-stem-cells
#7
Ravi Sonkar, Catherine A Powell, Mahua Choudhury
Endocrine disruptors, phthalates, may have contributed to recent global obesity health crisis. Our study investigated the potential of benzyl butyl phthalate (BBP) to regulate the mesenchymal stem cell epigenome to drive adipogenesis. BBP exposure enhanced lipid accumulation and adipogenesis in a dose-dependent manner compared to control (P < 0.001). Adipogenesis markers, PPARγ (P < 0.001), C/EBPα (P < 0.01), and aP2 (P < 0.001) were significantly upregulated by increasing concentrations of BBP when compared to DMSO...
May 6, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27057552/diabetes-mellitus-and-increased-tuberculosis-susceptibility-the-role-of-short-chain-fatty-acids
#8
Ekta Lachmandas, Corina N A M van den Heuvel, Michelle S M A Damen, Maartje C P Cleophas, Mihai G Netea, Reinout van Crevel
Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27004103/alterations-to-mtorc1-signaling-in-the-skeletal-muscle-differentially-affect-whole-body-metabolism
#9
Maitea Guridi, Barbara Kupr, Klaas Romanino, Shuo Lin, Denis Falcetta, Lionel Tintignac, Markus A Rüegg
BACKGROUND: The mammalian target of rapamycin complex 1 (mTORC1) is a central node in a network of signaling pathways controlling cell growth and survival. This multiprotein complex integrates external signals and affects different nutrient pathways in various organs. However, it is not clear how alterations of mTORC1 signaling in skeletal muscle affect whole-body metabolism. RESULTS: We characterized the metabolic phenotype of young and old raptor muscle knock-out (RAmKO) and TSC1 muscle knock-out (TSCmKO) mice, where mTORC1 activity in skeletal muscle is inhibited or constitutively activated, respectively...
2016: Skeletal Muscle
https://www.readbyqxmd.com/read/26885564/butyrate-production-from-high-fiber-diet-protects-against-lymphoma-tumor
#10
Wei Wei, Wei Sun, Shanshan Yu, Yu Yang, Limei Ai
Gut microbiota and dietary fiber are critical for protecting body from obesity, diabetes and cancer. Butyrate, produced in the gut by bacterial fermentation of dietary fibers, is demonstrated to be protective against the development of colorectal cancer as a histone deacetylase (HDAC) inhibitor. We report that high-fiber diet and butyrate significantly inhibited the growth lymphoma tumors. Butyrate induced apoptosis of lymphoma tumor cells and significantly up-regulated histone 3 acetylation (H3ac) level and target genes such as Fas, P21, P27...
October 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/26733201/histone-deacetylase-1-hdac1-negatively-regulates-thermogenic-program-in-brown-adipocytes-via-coordinated-regulation-of-histone-h3-lysine-27-h3k27-deacetylation-and-methylation
#11
Fenfen Li, Rui Wu, Xin Cui, Lin Zha, Liqing Yu, Hang Shi, Bingzhong Xue
Inhibiting class I histone deacetylases (HDACs) increases energy expenditure, reduces adiposity, and improves insulin sensitivity in obese mice. However, the precise mechanism is poorly understood. Here, we demonstrate that HDAC1 is a negative regulator of the brown adipocyte thermogenic program. The Hdac1 level is lower in mouse brown fat (BAT) than white fat, is suppressed in mouse BAT during cold exposure or β3-adrenergic stimulation, and is down-regulated during brown adipocyte differentiation. Remarkably, overexpressing Hdac1 profoundly blocks, whereas deleting Hdac1 significantly enhances, β-adrenergic activation-induced BAT-specific gene expression in brown adipocytes...
February 26, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26636769/upregulation-of-bone-morphogenetic-protein-2-synthesis-and-consequent-collagen-ii-expression-in-leptin-stimulated-human-chondrocytes
#12
Shun-Fu Chang, Rong-Ze Hsieh, Kuo-Chin Huang, Cheng Allen Chang, Fang-Yao Chiu, Hsing-Chun Kuo, Cheng-Nan Chen, Yu-Ping Su
Bone morphogenetic proteins (BMPs) play positive roles in cartilage development, but they can barely be detected in healthy articular cartilage. However, recent evidence has indicated that BMPs could be detected in osteoarthritic and damaged cartilage and their precise roles have not been well defined. Extremely high amounts of leptin have been reported in obese individuals, which can be associated with osteoarthritis (OA) development. The aim of this study was to investigate whether BMPs could be induced in human primary chondrocytes during leptin-stimulated OA development and the underlying mechanism...
2015: PloS One
https://www.readbyqxmd.com/read/26525534/phosphoproteomics-identifies-ck2-as-a-negative-regulator-of-beige-adipocyte-thermogenesis-and-energy-expenditure
#13
Kosaku Shinoda, Kana Ohyama, Yutaka Hasegawa, Hsin-Yi Chang, Mayu Ogura, Ayaka Sato, Haemin Hong, Takashi Hosono, Louis Z Sharp, David W Scheel, Mark Graham, Yasushi Ishihama, Shingo Kajimura
Catecholamines promote lipolysis both in brown and white adipocytes, whereas the same stimuli preferentially activate thermogenesis in brown adipocytes. Molecular mechanisms for the adipose-selective activation of thermogenesis remain poorly understood. Here, we employed quantitative phosphoproteomics to map global and temporal phosphorylation profiles in brown, beige, and white adipocytes under β3-adrenenoceptor activation and identified kinases responsible for the adipose-selective phosphorylation profiles...
December 1, 2015: Cell Metabolism
https://www.readbyqxmd.com/read/26457241/-curcumin-the-king-of-spices-epigenetic-regulatory-mechanisms-in-the-prevention-of-cancer-neurological-and-inflammatory-diseases
#14
Sarandeep S S Boyanapalli, Ah-Ng Tony Kong
Curcumin (diferuloylmethane), a polyphenolic compound, is a component of Curcuma longa, commonly known as turmeric. It is a well-known anti-inflammatory, anti-oxidative, and anti-lipidemic agent and has recently been shown to modulate several diseases via epigenetic regulation. Many recent studies have demonstrated the role of epigenetic inactivation of pivotal genes that regulate human pathologies, such as neurocognitive disorders, inflammation, obesity, and cancers. Epigenetic changes involve changes in DNA methylation, histone modifications, or altered microRNA expression patterns which are known to be interconnected and play a key role in tumor progression and failure of conventional chemotherapy...
April 2015: Current Pharmacology Reports
https://www.readbyqxmd.com/read/26317058/role-of-histone-deacetylase-9-in-regulating-adipogenic-differentiation-and-high-fat-diet-induced-metabolic-disease
#15
Tapan K Chatterjee, Joshua E Basford, Kan Hui Yiew, David W Stepp, David Y Hui, Neal L Weintraub
Adipose tissue serves as both a storage site for excess calories and as an endocrine organ, secreting hormones such as adiponectin that promote metabolic homeostasis. In obesity, adipose tissue expands primarily by hypertrophy (enlargement of existing adipocytes) rather than hyperplasia (generation of new adipocytes via adipogenic differentiation of preadipocytes). Progressive adipocyte hypertrophy leads to inflammation, insulin resistance, dyslipidemia, and ectopic lipid deposition, the hallmark characteristics of metabolic disease...
October 2014: Adipocyte
https://www.readbyqxmd.com/read/26109312/histone-deacetylase-4-promotes-cholestatic-liver-injury-in-the-absence-of-prohibitin-1
#16
Lucía Barbier-Torres, Naiara Beraza, Pablo Fernández-Tussy, Fernando Lopitz-Otsoa, David Fernández-Ramos, Imanol Zubiete-Franco, Marta Varela-Rey, Teresa C Delgado, Virginia Gutiérrez, Juan Anguita, Albert Pares, Jesús M Banales, Erica Villa, Juan Caballería, Luis Alvarez, Shelly C Lu, Jose M Mato, María Luz Martínez-Chantar
UNLABELLED: Prohibitin-1 (PHB1) is an evolutionarily conserved pleiotropic protein that participates in diverse processes depending on its subcellular localization and interactome. Recent data have indicated a diverse role for PHB1 in the pathogenesis of obesity, cancer, and inflammatory bowel disease, among others. Data presented here suggest that PHB1 is also linked to cholestatic liver disease. Expression of PHB1 is markedly reduced in patients with primary biliary cirrhosis and biliary atresia or with Alagille syndrome, two major pediatric cholestatic conditions...
October 2015: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/26053034/the-phosphorylated-prodrug-fty720-is-a-histone-deacetylase-inhibitor-that-reactivates-er%C3%AE-expression-and-enhances-hormonal-therapy-for-breast-cancer
#17
N C Hait, D Avni, A Yamada, M Nagahashi, T Aoyagi, H Aoki, C I Dumur, Z Zelenko, E J Gallagher, D Leroith, S Milstien, K Takabe, S Spiegel
Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and does not respond to conventional hormonal therapies. Strategies that lead to re-expression of ERα could sensitize ERα-negative breast cancers to selective ER modulators. FTY720 (fingolimod, Gilenya), a sphingosine analog, is the Food and Drug Administration (FDA)-approved prodrug for treatment of multiple sclerosis that also has anticancer actions that are not yet well understood. We found that FTY720 is phosphorylated in breast cancer cells by nuclear sphingosine kinase 2 and accumulates there...
June 8, 2015: Oncogenesis
https://www.readbyqxmd.com/read/25875123/dietary-gut-microbial-metabolites-short-chain-fatty-acids-and-host-metabolic-regulation
#18
REVIEW
Mayu Kasubuchi, Sae Hasegawa, Takero Hiramatsu, Atsuhiko Ichimura, Ikuo Kimura
During feeding, the gut microbiota contributes to the host energy acquisition and metabolic regulation thereby influencing the development of metabolic disorders such as obesity and diabetes. Short-chain fatty acids (SCFAs) such as acetate, butyrate, and propionate, which are produced by gut microbial fermentation of dietary fiber, are recognized as essential host energy sources and act as signal transduction molecules via G-protein coupled receptors (FFAR2, FFAR3, OLFR78, GPR109A) and as epigenetic regulators of gene expression by the inhibition of histone deacetylase (HDAC)...
April 2015: Nutrients
https://www.readbyqxmd.com/read/25320182/short-chain-fatty-acids-enhance-adipocyte-differentiation-in-the-stromal-vascular-fraction-of-porcine-adipose-tissue
#19
Genlai Li, Wen Yao, Honglin Jiang
BACKGROUND: Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are the main products of microbial fermentation in the gut and might mediate some of the effects of gut microbiota and nutrition on development, metabolism, and pathogenesis of obesity and other diseases. OBJECTIVE: The objective of this study was to determine the effects of SCFAs on adipocyte differentiation and the underlying mechanism. METHODS: The stromal vascular fraction (SVF) of the porcine subcutaneous fat was used as the preadipocyte model...
December 2014: Journal of Nutrition
https://www.readbyqxmd.com/read/25203139/inactivation-of-histone-deacetylase-1-hdac1-but-not-hdac2-is-required-for-the-glucocorticoid-dependent-ccaat-enhancer-binding-protein-%C3%AE-c-ebp%C3%AE-expression-and-preadipocyte-differentiation
#20
Claire Kuzmochka, Houssein-Salem Abdou, Robert J G Haché, Ella Atlas
Several drugs currently used in the management of mood disorders, epilepsy (ie, valproic acid), or the control of inflammation (ie, corticosteroids) have been shown to promote visceral obesity in humans by increasing the number of newly formed adipocytes. Valproic acid is classified as a nonspecific histone deacetylase (HDAC) inhibitor, along with trichostatin A and butyric acid. In vitro experiments have demonstrated that such molecules greatly enhance the rate of preadipocyte differentiation, similarly to the effect of corticosteroids...
December 2014: Endocrinology
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