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histone deacetylase adipose

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
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
Sabbir Khan, Sandeep Kumar, Gopabandhu Jena
Recent evidences highlighted the role of histone deacetylases (HDACs) in insulin-resistance, gluconeogenesis and islet function. HDACs can modulate the expression of various genes, which directly or indirectly affect glucose metabolism. This study was aimed to evaluate the role of valproic acid (VPA) on fat deposition, insulin-resistance and gluconeogenesis in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet and low dose streptozotocin. VPA at the doses of 150 and 300 mg/kg/day and metformin (positive control) 150 mg/kg twice daily for 10 weeks were administered by oral gavage...
June 2016: Biochimie
Dan Yang, Haimei Chen, Xu Zeng, Ping Xie, Xincun Wang, Chang Liu
BACKGROUND/AIMS: Comparative gene identification-58 (CGI-58), an adipose triglyceride lipase (ATGL) coactivator, strongly promotes ATGL-mediated triglyceride (TG) catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CGI-58 in the regulation of inflammatory responsiveness in macrophages. METHODS: Macrophage-specific GCI-58 transgenic mice (TG) and wild type mice (WT) were fed a high fat diet (HFD), and RAW264...
2016: Cellular Physiology and Biochemistry
Mina Desai, Guang Han, Michael G Ross
Maternal overnutrition results in programmed offspring obesity, mediated in part, by hyperphagia. This is remarkably similar to the effects of maternal undernutrition on offspring hyperphagia and obesity. In view of the marked differences in the energy environment of the over and under-nutrition exposures, we studied the expression of select epigenetic modifiers associated with energy imbalance including neurogenic factors and appetite/satiety neuropeptides which are indicative of neurogenic differentiation...
April 1, 2016: Appetite
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
Jienny Lee, Jeong Su Byeon, Keum Sil Lee, Na-Yeon Gu, Gyeong Been Lee, Hee-Ryang Kim, In-Soo Cho, Sang-Ho Cha
Mesenchymal stem cells (MSCs) have the ability to differentiate into multi-lineage cells, which confers great promise for use in regenerative medicine. In this study, canine adipose MSCs (cAD-MSCs) were isolated from canine adipose tissue. These cells clearly represented stemness (Oct4, Sox2, and Nanog) and differentiation potential into the mesoderm (adipocytes, chondrocytes, and osteoblasts) at early passages. The aim of this study was to evaluate the effects of hypoxia on the differentiation potential into mesoderm, and the expression of anti-apoptotic genes associated with cell survival for the optimal culturing of MSCs...
March 2016: Veterinary Research Communications
Ana Elena Peredo-Escárcega, Verónica Guarner-Lans, Israel Pérez-Torres, Sergio Ortega-Ocampo, Elizabeth Carreón-Torres, Vicente Castrejón-Tellez, Eulises Díaz-Díaz, María Esther Rubio-Ruiz
Resveratrol (RSV) and quercetin (QRC) modify energy metabolism and reduce cardiovascular risk factors included in the metabolic syndrome (MetS). These natural compounds upregulate and activate sirtuins (SIRTs), a family of NAD-dependent histone deacetylases. We analyzed the effect of two doses of a commercial combination of RSV and QRC on serum fatty acid composition and their regulation of SIRTs 1-3 and PPAR-γ expression in white adipose tissue. MetS was induced in Wistar rats by adding 30% sucrose to drinking water for five months...
2015: Evidence-based Complementary and Alternative Medicine: ECAM
I S Stafeev, M Y Menshikov, Z I Tsokolaeva, M V Shestakova, Ye V Parfyonova
The problem of metabolic syndrome is one of the most important in medicine today. The main hazard of metabolic syndrome is development of latent inflammation in adipose tissue, which promotes atherosclerosis, non-alcoholic fatty liver disease, myocarditis, and a number of other illnesses. Therefore, understanding of molecular mechanisms of latent inflammation in adipose tissue is very important for treatment of metabolic syndrome. Three main components that arise during hypertrophy and hyperplasia of adipocytes underlie such inflammation: endoplasmic reticulum stress, oxidative stress, and hypoxia...
October 2015: Biochemistry. Biokhimii︠a︡
Yu-Chou Tseng, Samuel K Kulp, I-Lu Lai, En-Chi Hsu, Wei A He, David E Frankhouser, Pearlly S Yan, Xiaokui Mo, Mark Bloomston, Gregory B Lesinski, Guido Marcucci, Denis C Guttridge, Tanios Bekaii-Saab, Ching-Shih Chen
BACKGROUND: Cancer cachexia is a debilitating condition that impacts patient morbidity, mortality, and quality of life and for which effective therapies are lacking. The anticachectic activity of the novel HDAC inhibitor AR-42 was investigated in murine models of cancer cachexia. METHODS: The effects of AR-42 on classic features of cachexia were evaluated in the C-26 colon adenocarcinoma and Lewis lung carcinoma (LLC) models. Effects on survival in comparison with approved HDAC inhibitors (vorinostat, romidepsin) were determined...
December 2015: Journal of the National Cancer Institute
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
Ling Gan, Emily England, Jeong-Yeh Yang, Natalie Toulme, Suresh Ambati, Diane L Hartzell, Richard B Meagher, Clifton A Baile
BACKGROUND: Recent evidence identifies the hippocampus, a brain structure commonly associated with learning and memory, as key to the regulation of food intake and the development and consequences of obesity. Intake of a high fat diet (HFD) results in altered consumptive behavior, hippocampal damage, and cognitive deficits. While many studies report the effects of HFD after chronic consumption and in the instance of obesity, few examine the events that occur following acute HFD consumption...
2015: BMC Neuroscience
Tsutomu Sasaki
The hypothalamus is the principal regulator of body weight and energy balance. It modulates both energy intake and energy expenditure by sensing the energy status of the body through neural inputs from the periphery as well as direct humoral inputs. Leptin, an adipokine, is one of the humoral factors responsible for alerting the hypothalamus that enough energy is stored in the periphery. Plasma leptin levels are positively linked to adiposity; leptin suppress energy intake and stimulates energy expenditure...
2015: Frontiers in Endocrinology
Meghan E McGee-Lawrence, Lomeli R Carpio, Ryan J Schulze, Jessica L Pierce, Mark A McNiven, Joshua N Farr, Sundeep Khosla, Merry Jo Oursler, Jennifer J Westendorf
Bone loss and increased marrow adiposity are hallmarks of aging skeletons. Conditional deletion of histone deacetylase 3 (Hdac3) in murine osteochondroprogenitor cells causes osteopenia and increases marrow adiposity, even in young animals, but the origins of the increased adiposity are unclear. To explore this, bone marrow stromal cells (BMSCs) from Hdac3-depleted and control mice were cultured in osteogenic medium. Hdac3-deficient cultures accumulated lipid droplets in greater abundance than control cultures and expressed high levels of genes related to lipid storage (Fsp27/Cidec, Plin1) and glucocorticoid metabolism (Hsd11b1) despite normal levels of Pparγ2...
January 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Sekyu Choi, Dae-Sik Lim, Jongkyeong Chung
LKB1 plays important roles in governing energy homeostasis by regulating AMP-activated protein kinase (AMPK) and other AMPK-related kinases, including the salt-inducible kinases (SIKs). However, the roles and regulation of LKB1 in lipid metabolism are poorly understood. Here we show that Drosophila LKB1 mutants display decreased lipid storage and increased gene expression of brummer, the Drosophila homolog of adipose triglyceride lipase (ATGL). These phenotypes are consistent with those of SIK3 mutants and are rescued by expression of constitutively active SIK3 in the fat body, suggesting that SIK3 is a key downstream kinase of LKB1...
May 2015: PLoS Genetics
Rafael Mayoral, Olivia Osborn, Joanne McNelis, Andrew M Johnson, Da Young Oh, Cristina Llorente Izquierdo, Heekyung Chung, Pingping Li, Paqui G Traves, Gautam Bandyopadhyay, Ariane R Pessentheiner, Jachelle M Ofrecio, Joshua R Cook, Li Qiang, Domenico Accili, Jerrold M Olefsky
OBJECTIVE: Adipose tissue is the primary site for lipid deposition that protects the organisms in cases of nutrient excess during obesogenic diets. The histone deacetylase Sirtuin 1 (SIRT1) inhibits adipocyte differentiation by targeting the transcription factor peroxisome proliferator activated-receptor gamma (PPARγ). METHODS: To assess the specific role of SIRT1 in adipocytes, we generated Sirt1 adipocyte-specific knockout mice (ATKO) driven by aP2 promoter onto C57BL/6 background...
May 2015: Molecular Metabolism
Cheng Xu, Yu Cai, Pengcheng Fan, Bo Bai, Jie Chen, Han-Bing Deng, Chi-Ming Che, Aimin Xu, Paul M Vanhoutte, Yu Wang
Adipose tissue is a pivotal organ determining longevity, due largely to its role in maintaining whole-body energy homeostasis and insulin sensitivity. SIRT1 is a NAD-dependent protein deacetylase possessing antiaging activities in a wide range of organisms. The current study demonstrates that mice with adipose tissue-selective overexpression of hSIRT1(H363Y), a dominant-negative mutant that disrupts endogenous SIRT1 activity, show accelerated development of metabolic aging. These mice, referred to as Adipo-H363Y, exhibit hyperglycemia, dyslipidemia, ectopic lipid deposition, insulin resistance, and glucose intolerance at a much younger age than their wild-type littermates...
May 2015: Diabetes
Emma Henriksson, Johanna Säll, Amélie Gormand, Sebastian Wasserstrom, Nicholas A Morrice, Andreas M Fritzen, Marc Foretz, David G Campbell, Kei Sakamoto, Mikael Ekelund, Eva Degerman, Karin G Stenkula, Olga Göransson
Salt-inducible kinase 2 (SIK2) is an AMP-activated protein kinase (AMPK) related kinase abundantly expressed in adipose tissue. Our aim was to identify molecular targets and functions of SIK2 in adipocytes, and to address the role of PKA-mediated phosphorylation of SIK2 on Ser358. Modulation of SIK2 in adipocytes resulted in altered phosphorylation of CREB-regulated transcription co-activator 2 (CRTC2), CRTC3 and class IIa histone deacetylase 4 (HDAC4). Furthermore, CRTC2, CRTC3, HDAC4 and protein phosphatase 2A (PP2A) interacted with SIK2, and the binding of CRTCs and PP2A to wild-type but not Ser358Ala SIK2, was reduced by cAMP elevation...
February 1, 2015: Journal of Cell Science
Venkat N Vangaveti, Catherine Rush, Linda Thomas, Roy R Rasalam, Usman H Malabu, Scott G McCoombe, Richard L Kennedy
OBJECTIVE: Stromal cell-derived factor-1 (SDF-1) is expressed in pre-adipocytes but its role is unknown. We investigated butyrate (a histone deacetylase inhibitor--HDACi) and other short-chain fatty acids (SCFA) in the regulation of SDF-1. We further investigated whether effects of SCFA were signalled through G protein-coupled receptors FFA2 and FFA3. DESIGN AND RESULTS: SDF-1 mRNA expression and protein secretion were studied in 3T3-L1 cells and human pre-adipocytes...
October 2014: Hormones: International Journal of Endocrinology and Metabolism
Sun-O Ka, Mi-Young Song, Eun Ju Bae, Byung-Hyun Park
Inflammation is an important factor in the development of insulin resistance. SIRT1, a class 3 histone/protein deacetylase, has anti-inflammatory functions. Myeloid-specific deletion of Sirt1 promotes macrophage infiltration into insulin-sensitive organs and aggravates tissue inflammation. In this study, we investigated how SIRT1 in macrophages alters tissue inflammation in the pancreas as well as liver and adipose tissue, and further explored the role of SIRT1 in locomotion of macrophages. Myeloid-specific Sirt1-deleted mice (mS1KO) and WT littermates were fed a 60% calorie high-fat diet (HFD) for 16 weeks...
February 2015: Journal of Endocrinology
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