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histone deacetylase adipose

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https://www.readbyqxmd.com/read/28916721/loss-of-cardiac-carnitine-palmitoyltransferase-2-results-in-rapamycin-resistant-acetylation-independent-hypertrophy
#1
Andrea S Pereyra, Like Y Hasek, Kate L Harris, Alycia G Berman, Frederick W Damen, Craig J Goergen, Jessica M Ellis
Cardiac hypertrophy is closely linked to impaired fatty acid oxidation, but the molecular basis of this link is unclear. Here, we investigated the loss of an obligate enzyme in mitochondrial long-chain fatty acid oxidation, carnitine palmitoyltransferase 2 (CPT2), on muscle and heart structure, function, and molecular signatures in a muscle- and heart-specific CPT2-deficient mouse (Cpt2M-/-) model. CPT2 loss in heart and muscle reduced complete oxidation of long-chain fatty acids by 87% and 69%, respectively, without altering body weight, energy expenditure, respiratory quotient, or adiposity...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28882900/adipocyte-liver-kinase-b1-suppresses-beige-adipocyte-renaissance-through-class-iia-histone-deacetylase-4
#2
Yangmeng Wang, Esther Paulo, Dongmei Wu, Yixuan Wu, Wendong Huang, Ajay Chawla, Biao Wang
Uncoupling protein 1(+) (UCP1(+)) beige adipocytes are dynamically regulated by environment in rodents and humans; cold induces formation of beige adipocytes, while warm temperature and nutrient excess lead to their disappearance. Beige adipocytes can form through de novo adipogenesis, however how "beigeing" characteristics are maintained afterwards is largely unknown. Here we show that beige adipocytes formed postnatally in subcutaneous inguinal white adipose tissue (iWAT) lost thermogenic gene expression and multilocular morphology at adult stage, but cold restored their "beigeing" characteristics, a phenomenon termed as beige adipocyte renaissance...
September 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28860191/isoform-selective-inhibitor-of-histone-deacetylase-3-hdac3-limits-pancreatic-islet-infiltration-and-protects-female-nonobese-diabetic-mice-from-diabetes
#3
Ercument Dirice, Raymond Ng, Rachael Martinez, Jiang Hu, Florence F Wagner, Edward B Holson, Bridget K Wagner, Rohit N Kulkarni
Preservation of insulin-secreting β-cells is an important goal for therapies aimed at restoring normoglycemia in patients with diabetes. One approach, the inhibition of histone deacetylases (HDACs), has been reported to suppress pancreatic islet inflammation and β-cell apoptosis in vitro. In this report, we demonstrate the efficacy of HDAC inhibitors (HDACi) in vivo. We show that daily administration of BRD3308, an isoform-selective HDAC3 inhibitor, for 2 weeks to female nonobese diabetic (NOD) mice, beginning at 3 weeks of age, followed by twice-weekly injections until age 25 weeks, protects the animals from diabetes...
August 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28733645/hdac3-is-a-molecular-brake-of-the-metabolic-switch-supporting-white-adipose-tissue-browning
#4
Alessandra Ferrari, Raffaella Longo, Erika Fiorino, Rui Silva, Nico Mitro, Gaia Cermenati, Federica Gilardi, Béatrice Desvergne, Annapaola Andolfo, Cinzia Magagnotti, Donatella Caruso, Emma De Fabiani, Scott W Hiebert, Maurizio Crestani
White adipose tissue (WAT) can undergo a phenotypic switch, known as browning, in response to environmental stimuli such as cold. Post-translational modifications of histones have been shown to regulate cellular energy metabolism, but their role in white adipose tissue physiology remains incompletely understood. Here we show that histone deacetylase 3 (HDAC3) regulates WAT metabolism and function. Selective ablation of Hdac3 in fat switches the metabolic signature of WAT by activating a futile cycle of de novo fatty acid synthesis and β-oxidation that potentiates WAT oxidative capacity and ultimately supports browning...
July 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28698144/inhibiting-glycogen-synthase-kinase-3-and-transforming-growth-factor-%C3%AE-signaling-to-promote-epithelial-transition-of-human-adipose-mesenchymal-stem-cells
#5
Melina Setiawan, Xiao-Wei Tan, Tze-Wei Goh, Gary Hin-Fai Yam, Jodhbir S Mehta
BACKGROUND: This study was aimed to investigate the epithelial differentiation of human adipose-derived mesenchymal stem cells (ADSCs) by inhibiting glycogen synthase kinase-3 (GSK3) and transforming growth factor β (TGFβ) signaling. METHODS AND RESULTS: STEMPRO human ADSCs at passage 2 were treated with CHIR99021 (GSK3 inhibitor), E-616452 (TGFβ1 receptor kinase inhibitor), A-83-01 (TGFβ type 1 receptor inhibitor), valproic acid (histone deacetylase inhibitor), tranylcypromine (monoamine oxidase inhibitor) and all-trans retinoic acid for 72 h...
September 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28663238/remarkable-evolutionary-conservation-of-antiobesity-adipose-wdtc1-homologs-in-animals-and-plants
#6
Eric Ducos, Valentin Vergès, Thomas Dugé de Bernonville, Nathalie Blanc, Nathalie Giglioli-Guivarc'h, Christelle Dutilleul
ASG2 (Altered Seed Germination 2) is a prenylated protein in Arabidopsis thaliana that participates to abscisic acid signaling and is proposed to act as a substrate adaptor for the DDB1 (DNA damage-binding protein 1)-CUL4 (Cullin 4) E3 ubiquitin ligase complex. ASG2 harbors WD40 and TetratricoPeptide Repeat (TPR) domains, and resembles the well-conserved animal gene called ADP (antiobesity factor ADIPOSE) in fly and WDTC1 (WD40 and TPR 1) in humans. Loss of function of WDTC1 results in an increase in adipocytes, fat accumulation, and obesity...
September 2017: Genetics
https://www.readbyqxmd.com/read/28614293/histone-deacetylase-3-prepares-brown-adipose-tissue-for-acute-thermogenic-challenge
#7
Matthew J Emmett, Hee-Woong Lim, Jennifer Jager, Hannah J Richter, Marine Adlanmerini, Lindsey C Peed, Erika R Briggs, David J Steger, Tao Ma, Carrie A Sims, Joseph A Baur, Liming Pei, Kyoung-Jae Won, Patrick Seale, Zachary Gerhart-Hines, Mitchell A Lazar
Brown adipose tissue is a thermogenic organ that dissipates chemical energy as heat to protect animals against hypothermia and to counteract metabolic disease. However, the transcriptional mechanisms that determine the thermogenic capacity of brown adipose tissue before environmental cold are unknown. Here we show that histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude. Mice with brown adipose tissue-specific genetic ablation of HDAC3 become severely hypothermic and succumb to acute cold exposure...
June 22, 2017: Nature
https://www.readbyqxmd.com/read/28610961/histone-acetylation-favours-the-cardiovascular-commitment-of-adipose-tissue-derived-stromal-cells
#8
Elena De Falco, Antonella Bordin, Eleonora Scaccia, Francesca Pagano, Mohsen Ibrahim, Leonardo Schirone, Francesco Angelini, Silvia Palmerio, Michele Madonna, Luca Fianchini, Isotta Chimenti, Sebastiano Sciarretta, Giacomo Frati
BACKGROUND: Although adipose stromal cells (ASCs) retain the ability to transdifferentiate at low rate towards the cardiac lineage, the potential mechanisms underlying such process have still to be elucidated. METHODS: Since chromatin state modifications are involved in several processes regulating the cellular cell fate commitment, we aimed at evaluating the role of histone protein acetylation in the cardiovascular-like transdifferentiation of ASCs. RESULTS: We found a clear increase of histone 3 acetylation status paralleled by a significant upregulation of cardiac TnI gene expression, in ASCs treated with the conditioned medium of primary cardiomyocyte cell cultures for 72h...
September 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28489652/histone-deacetylase-inhibitors-enhance-cytotoxicity-towards-breast-tumors-while-preserving-the-wound-healing-function-of-adipose-derived-stem-cells
#9
Kiavash R Koko, Shaohua Chang, Ashleigh L Hagaman, Marc W Fromer, Ryan S Nolan, John P Gaughan, Ping Zhang, Jeffrey P Carpenter, Spencer A Brown, Martha Matthews, Dorothy Bird
INTRODUCTION: Paclitaxel improves the oncologic response of breast cancer resections; however, it may negatively affect the wound-healing potential of human adipose-derived stem cells (hASCs) for fat grafting and reconstructive surgery. Histone deacetylase inhibitors (HDACis) modify the epigenetic regulation of gene expression and stabilize microtubules similarly to paclitaxel, thus, creating a synergistic mechanism of cell cycle arrest. We aim to combine these drugs to enhance cytotoxicity towards breast cancer cells, while preserving the wound-healing function of hASCs for downstream reconstructive applications...
June 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28287402/hdac6-mediated-acetylation-of-lipid-droplet-binding-protein-cidec-regulates-fat-induced-lipid-storage
#10
Hui Qian, Yuanying Chen, Zongqian Nian, Lu Su, Haoyong Yu, Feng-Jung Chen, Xiuqin Zhang, Wenyi Xu, Linkang Zhou, Jiaming Liu, Jinhai Yu, Luxin Yu, Yan Gao, Hongchao Zhang, Haihong Zhang, Shimin Zhao, Li Yu, Rui-Ping Xiao, Yuqian Bao, Shaocong Hou, Pingping Li, Jiada Li, Haiteng Deng, Weiping Jia, Peng Li
Obesity is characterized by aberrant fat accumulation. However, the intracellular signaling pathway that senses dietary fat and leads to fat storage remains elusive. Here, we have observed that the levels of histone deacetylase 6 (HDAC6) and the related family member HDAC10 are markedly reduced in adipose tissues of obese animals and humans. Mice with adipocyte-specific depletion of Hdac6 exhibited increased fat accumulation and reduced insulin sensitivity. In normal adipocytes, we found that reversal of P300/CBP-associated factor-induced (PCAF-induced) acetylation at K56 on cell death-inducing DFFA-like effector C (CIDEC, also known as FSP27) critically regulated lipid droplet fusion and lipid storage...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28107769/the-transcriptional-modulator-ifrd1-controls-pgc-1%C3%AE-expression-under-short-term-adrenergic-stimulation-in-brown-adipocytes
#11
Gyujin Park, Tetsuhiro Horie, Takashi Kanayama, Kazuya Fukasawa, Takashi Iezaki, Yuki Onishi, Kakeru Ozaki, Yukari Nakamura, Yukio Yoneda, Takeshi Takarada, Eiichi Hinoi
Sympathetic tone activates the function of classical brown adipocytes, which constitutively exist in the brown adipose tissue (BAT), and inducible brown adipocytes (so-called beige adipocytes), which sporadically reside within the white adipose tissue (WAT). Here we identified the transcriptional modulator interferon-related developmental regulator 1 (Ifrd1) as a negative regulator of thermogenic and mitochondrial gene expression in brown adipocytes. Ifrd1 expression was markedly induced by cold exposure and administration of CL-316243 (a β3 adrenergic agonist) in interscapular brown adipose and inguinal subcutaneous WATs, but not in epididymal visceral WAT, in vivo...
March 2017: FEBS Journal
https://www.readbyqxmd.com/read/27987529/melatonin-promotes-circadian-rhythm-induced-proliferation-through-clock-histone-deacetylase-3-c-myc-interaction-in-mouse-adipose-tissue
#12
Zhenjiang Liu, Lu Gan, Dan Luo, Chao Sun
Melatonin is synthesized in the pineal gland and controls circadian rhythm of peripheral adipose tissue, resulting in changes in body weight. Although core regulatory components of clock rhythmicity have been defined, insight into the mechanisms of circadian rhythm-mediated proliferation in adipose tissue is still limited. Here, we showed that melatonin (20 mg/kg/d) promoted circadian and proliferation processes in white adipose tissue. The circadian amplitudes of brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1, P<...
May 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/27900262/impaired-histone-deacetylases-5-and-6-expression-mimics-the-effects-of-obesity-and-hypoxia-on-adipocyte-function
#13
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/27875543/irisin-ameliorates-hypoxia-reoxygenation-induced-injury-through-modulation-of-histone-deacetylase-4
#14
Yu Tina Zhao, Hao Wang, Shouyan Zhang, Jianfeng Du, Shougang Zhuang, Ting C Zhao
Irisin is a recently identified myokine which brings increases in energy expenditure and contributes to the beneficial effects of exercise through the browning of white adipose tissues. However, its effects in the heart remains unknown. This study sought to determine the effects of irisin on hypoxia/reoxygenation injury and its relationship with HDAC4. Wild type and stable HDAC4-overexpression cells were generated from H9c2 cardiomyoblasts. HDAC4 overexpression cells and wild type H9c2 cells were exposed to 24 hours of hypoxia followed by one hour of reoxygenation in vitro in the presence or absence of irisin (5 ng/ml)...
2016: PloS One
https://www.readbyqxmd.com/read/27861911/metabolism-of-ketone-bodies-during-exercise-and-training-physiological-basis-for-exogenous-supplementation
#15
Mark Evans, Karl E Cogan, Brendan Egan
Optimising training and performance through nutrition strategies is central to supporting elite sportspeople, much of which has focused on manipulating the relative intake of carbohydrate and fat and their contributions as fuels for energy provision. The ketone bodies, namely acetoacetate, acetone and β-hydroxybutyrate (βHB), are produced in the liver during conditions of reduced carbohydrate availability and serve as an alternative fuel source for peripheral tissues including brain, heart and skeletal muscle...
May 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/27819724/histone-h3k9-acetylation-influences-growth-characteristics-of-goat-adipose-derived-stem-cells-in-vitro
#16
X Wang, F X Zhang, Z M Wang, Q Wang, H F Wang, Y Ren, D P Tai, H Liang, D J Liu
Adipose-derived stem cells (ADSCs) show nearly unlimited potential in medical and animal science. Currently, understanding of the biological mechanisms regulating ADSC growth in vitro remains very limited. Histone acetylation, an epigenetic modification, plays a key role in maintaining stem cell properties. To further study its effect on ADSC growth characteristics in vitro, we treated goat ADSCs with the histone deacetylase inhibitors trichostatin A (TSA) and vorinostat (SAHA). This inhibited SIRT1 expression and increased histone H3K9 acetylation, leading to decreased cell viability, cell cycle arrest, and apoptosis...
November 3, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27807598/salt-inducible-kinase-2-and-3-are-downregulated-in-adipose-tissue-from-obese-or-insulin-resistant-individuals-implications-for-insulin-signalling-and-glucose-uptake-in-human-adipocytes
#17
Johanna Säll, Annie M L Pettersson, Christel Björk, Emma Henriksson, Sebastian Wasserstrom, Wilhelm Linder, Yuedan Zhou, Ola Hansson, Daniel P Andersson, Mikael Ekelund, Eva Degerman, Karin G Stenkula, Jurga Laurencikiene, Olga Göransson
AIMS/HYPOTHESIS: Salt-inducible kinases (SIKs) are related to the metabolic regulator AMP-activated protein kinase (AMPK). SIK2 is abundant in adipose tissue. The aims of this study were to investigate the expression of SIKs in relation to human obesity and insulin resistance, and to evaluate whether changes in the expression of SIKs might play a causal role in the development of disturbed glucose uptake in human adipocytes. METHODS: SIK mRNA and protein was determined in human adipose tissue or adipocytes, and correlated to clinical variables...
February 2017: Diabetologia
https://www.readbyqxmd.com/read/27795551/attenuation-of-diet-induced-obesity-and-induction-of-white-fat-browning-with-a-chemical-inhibitor-of-histone-deacetylases
#18
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 dimethylsulfoxide (DMSO) or with the class I selective HDAC inhibitor MS-275 every other day for 22 days...
February 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27270450/sodium-butyrate-reduces-insulin-resistance-fat-accumulation-and-dyslipidemia-in-type-2-diabetic-rat-a-comparative-study-with-metformin
#19
COMPARATIVE STUDY
Sabbir Khan, Gopabandhu Jena
Recent evidences highlighted that histone deacetylases (HDACs) can deacetylate the histone, various transcription factors and regulatory proteins, which directly or indirectly affect glucose metabolism. The present study aimed to evaluate the comparative effects of sodium butyrate (NaB) and metformin on the glucose homeostasis, insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet (HFD) and low dose streptozotocin (STZ, 35 mg/kg)...
July 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27247940/a-drosophila-model-for-screening-antiobesity-agents
#20
Tran Thanh Men, Duong Ngoc Van Thanh, Masamitsu Yamaguchi, Takayoshi Suzuki, Gen Hattori, Masayuki Arii, Nguyen Tien Huy, Kaeko Kamei
Although triacylglycerol, the major component for lipid storage, is essential for normal physiology, its excessive accumulation causes obesity in adipose tissue and is associated with organ dysfunction in nonadipose tissue. Here, we focused on the Drosophila model to develop therapeutics for preventing obesity. The brummer (bmm) gene in Drosophila melanogaster is known to be homologous with human adipocyte triglyceride lipase, which is related to the regulation of lipid storage. We established a Drosophila model for monitoring bmm expression by introducing the green fluorescent protein (GFP) gene as a downstream reporter of the bmm promoter...
2016: BioMed Research International
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