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histone deacetylase adipose

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https://www.readbyqxmd.com/read/29757434/hdac3-selective-inhibition-activates-brown-and-beige-fat-through-prdm16
#1
Jiling Liao, Juan Jiang, Heejin Jun, Xiaona Qiao, Margo P Emont, Dong-Il Kim, Jun Wu
It has been reported that class I histone deacetylase (HDAC) inhibition increases thermogenesis in fat, but adipocyte specific Hdac3 deletions have presented inconsistent results. In this study, we observed that HDAC3 protein levels were lower in brown fat compared to that of inguinal subcutaneous adipose tissue, and were decreased in both fat depots upon cold exposure. PRDM16 physically interacted with HDAC3, and treatment with HDAC3-selective inhibitor RGFP966 induced thermogenic gene expression in murine and human fat cultures...
May 10, 2018: Endocrinology
https://www.readbyqxmd.com/read/29517636/a-new-2-step-acceleration-protocol-using-a-histone-deacetylase-inhibitor-to-generate-insulin-producing-cells-from-adipose-derived-mesenchymal-stem-cells
#2
Tetsuya Ikemoto, Rui Feng, Mitsuo Shimada, Yu Saito, Shuichi Iwahashi, Yuji Morine, Satoru Imura
OBJECTIVES: We aimed to develop a simple protocol for deriving insulin-producing cells (IPCs) from adipose-derived mesenchymal stem cells (ADSCs). We established a 2-step creation method and an acceleration strategy with a histone deacetylase inhibitor that promoted a pro-endocrine pancreatic lineage. METHODS: We seeded ADSCs in 96-well dishes and cultured in Dulbecco's modified Eagle's medium/F12 medium containing 1% fetal bovine serum, 1% B27 supplement, 1% N2 supplement, 50-ng/mL human activin A, and 10-nM exendin-4 for step 1 of differentiation (7 days)...
April 2018: Pancreas
https://www.readbyqxmd.com/read/29482257/histone-deacetylase-inhibitor-trapoxin-a-enhances-stemness-properties-in-adipose-tissue-derived-mesenchymal-stem-cells
#3
Leila Mousazadeh, Effat Alizadeh, Nosratollah Zarghami, Shahryar Hashemzadeh, Sedigheh Fekri Aval, Leili Hasanifard, Roya Herizchi
BACK GROUND: Adipose tissue derived mesenchymal stem cells (ASCs) have unique potential for regenerative cell therapies. However, during ex-vivo cultivation, they undergo considerable quality loss regarding their phenotypic properties, stemness genes expression and differentiation potential. Recent studies reported that the loss of stemness properties of MSCs is a result of chromatin histone deacetylations through in-vitro cultivation. The present work aimed to study the effect of Trapoxin A (TPX) as a histone deacetylase inhibitor (HDACi) on overall stemness properties of ASCs...
February 26, 2018: Drug Research
https://www.readbyqxmd.com/read/29427626/leptin-induces-sirt1-expression-through-activation-of-nf-e2-related-factor-2-implications-for-obesity-associated-colon-carcinogenesis
#4
Na-Young Song, Yeon-Hwa Lee, Hye-Kyung Na, Jeong-Heum Baek, Young-Joon Surh
Leptin, a representative adipokine secreted from the white adipose tissue, is considered as a potential linker between obesity and cancer. SIRT1 is an NAD+ -dependent histone/protein deacetylase speculated to function as an oncogene. In the present study, we found that leptin signaling-defective ob/ob and db/db mice had lower colonic expression of SIRT1 compared with leptin signaling-intact C57BL/6J mice, implying that leptin signaling is crucial for SIRT1 expression in vivo. Moreover, leptin induced up-regulation of SIRT1 in human colon cancer (HCT-116) cells...
February 7, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29396182/primary-cilia-are-dysfunctional-in-obese-adipose-derived-mesenchymal-stem-cells
#5
Andreas Ritter, Alexandra Friemel, Nina-Naomi Kreis, Samira Catharina Hoock, Susanne Roth, Ulrikke Kielland-Kaisen, Dörthe Brüggmann, Christine Solbach, Frank Louwen, Juping Yuan
Adipose-derived mesenchymal stem cells (ASCs) have crucial functions, but their roles in obesity are not well defined. We show here that ASCs from obese individuals have defective primary cilia, which are shortened and unable to properly respond to stimuli. Impaired cilia compromise ASC functionalities. Exposure to obesity-related hypoxia and cytokines shortens cilia of lean ASCs. Like obese ASCs, lean ASCs treated with interleukin-6 are deficient in the Hedgehog pathway, and their differentiation capability is associated with increased ciliary disassembly genes like AURKA...
February 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29386999/intermittent-fasting-alleviates-the-increase-of-lipoprotein-lipase-expression-in-brain-of-a-mouse-model-of-alzheimer-s-disease-possibly-mediated-by-%C3%AE-hydroxybutyrate
#6
Jingzhu Zhang, Xinhui Li, Yahao Ren, Yue Zhao, Aiping Xing, Congmin Jiang, Yanqiu Chen, Li An
Intermittent fasting has been demonstrated to protect against Alzheimer's disease (AD), however, the mechanism is unclear. Histone acetylation and lipoprotein lipase (LPL) are involved in AD progression. Importantly, LPL has been documented to be regulated by histone deacetylases (HDACs) inhibitors (increase histone acetylation level) in adipocyte and mesenchymal stem cells, or by fasting in adipose and muscle tissues. In brain, however, whether histone acetylation or fasting regulates LPL expression is unknown...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29298809/sucrose-nonfermenting-related-kinase-regulates-both-adipose-inflammation-and-energy-homeostasis-in-mice-and-humans
#7
Jie Li, Bin Feng, Yaohui Nie, Ping Jiao, Xiaochen Lin, Mengna Huang, Ran An, Qin He, Huilin Emily Zhou, Arthur Salomon, Kirsten S Sigrist, Zhidan Wu, Simin Liu, Haiyan Xu
Sucrose nonfermenting-related kinase (SNRK) is a member of the AMPK-related kinase family, and its physiological role in adipose energy homeostasis and inflammation remains unknown. We previously reported that SNRK is ubiquitously and abundantly expressed in both white adipose tissue (WAT) and brown adipose tissue (BAT), but SNRK expression diminishes in adipose tissue in obesity. In this study we report novel experimental findings from both animal models and human genetics. SNRK is essential for survival; SNRK globally deficient pups die within 24 h after birth...
March 2018: Diabetes
https://www.readbyqxmd.com/read/29189132/polyphenols-novel-signaling-pathways
#8
Marie-Louise Ricketts, Bradley S Ferguson
BACKGROUND: Cardiovascular disease (CVD) is currently the leading cause of death globally. The metabolic syndrome (MetS), a clustering of risk factors including hypertension, hyperglycemia, elevated low-density lipoprotein (LDL) cholesterol, reduced high-density lipoprotein (HDL) cholesterol and increased visceral adiposity, is a significant risk factor for the development of CVD. Non-alcoholic fatty liver disease (NAFLD), often referred to as the hepatic manifestation of MetS, is a constellation of progressive liver disorders closely linked to obesity, diabetes, and insulin resistance...
November 29, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29169361/differentiation-of-human-adipose-derived-stem-cells-into-cardiomyocyte-like-cells-in-fibrin-scaffold-by-a-histone-deacetylase-inhibitor
#9
Zahra Bagheri-Hosseinabadi, Parvin Salehinejad, Seyed Alireza Mesbah-Namin
BACKGROUND: Human adipose-derived stem cells (hADSCs) are capable of differentiating into many cells such as cardiac cells. Different types of inducers are used for cardiac cell differentiation, but this question still remains to be investigated, which one is the best. The aim of this paper was to investigate the effect of combination of fibrin scaffold and trichostatin A (TSA), for differentiation of hADSCs into cardiomyocyte-like cells. METHODS: After approval of characteristics of hADSCs and fibrin scaffold, hADSCs were cultured in fibrin scaffold with 10 µM TSA for 72 h and kept in standard conditions for 4 weeks...
November 23, 2017: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28916721/loss-of-cardiac-carnitine-palmitoyltransferase-2-results-in-rapamycin-resistant-acetylation-independent-hypertrophy
#10
COMPARATIVE STUDY
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...
November 10, 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
#11
Yangmeng Wang, Esther Paulo, Dongmei Wu, Yixuan Wu, Wendong Huang, Ajay Chawla, Biao Wang
Uncoupling protein 1+ beige adipocytes are dynamically regulated by environment in rodents and humans; cold induces formation of beige adipocytes, whereas warm temperature and nutrient excess lead to their disappearance. Beige adipocytes can form through de novo adipogenesis; however, how "beiging" characteristics are maintained afterward is largely unknown. In this study, we show that beige adipocytes formed postnatally in subcutaneous inguinal white adipose tissue lost thermogenic gene expression and multilocular morphology at the adult stage, but cold restored their beiging characteristics, a phenomenon termed beige adipocyte renaissance...
December 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
#12
Ercument Dirice, Raymond W S 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...
October 27, 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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