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histone deacetylase beige

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
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
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
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
Changchun Deng, Mark Lipstein, Richard Rodriguez, Xavier O Jirau Serrano, Christine McIntosh, Wei-Yann Tsai, Andrew S Wasmuth, Susan Jaken, Owen A O'Connor
PURPOSE: To evaluate the pharmacologic activity of a novel inhibitor of IκB kinase β (IKK2), LY2409881, in preclinical models of B- and T-cell lymphoma, as a single agent and in combination with histone deacetylase (HDAC) inhibitors. EXPERIMENTAL DESIGN: The in vitro activity of LY2409881 was determined using an ATP-based growth inhibition assay and flow cytometric assay of apoptosis in lymphoma cell lines. The in vivo activity of LY2409881 was determined using SCID-beige xenograft mouse model...
January 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Tapan K Chatterjee, Joshua E Basford, Ellen Knoll, Wilson S Tong, Victor Blanco, Andra L Blomkalns, Steven Rudich, Alex B Lentsch, David Y Hui, Neal L Weintraub
During chronic caloric excess, adipose tissue expands primarily by enlargement of individual adipocytes, which become stressed with lipid overloading, thereby contributing to obesity-related disease. Although adipose tissue contains numerous preadipocytes, differentiation into functionally competent adipocytes is insufficient to accommodate the chronic caloric excess and prevent adipocyte overloading. We report for the first time that a chronic high-fat diet (HFD) impairs adipogenic differentiation, leading to accumulation of inefficiently differentiated adipocytes with blunted expression of adipogenic differentiation-specific genes...
January 2014: Diabetes
Luca Paoluzzi, Luigi Scotto, Enrica Marchi, Jasmine Zain, Venkatraman E Seshan, Owen A O'Connor
PURPOSE: Romidepsin and belinostat are inhibitors of histone deacetylases (HDACI). HDACIs are known to induce cell death in malignant cells through multiple mechanisms, including upregulation of death receptors and induction of cell cycle arrest. They are also known to be prodifferentiating. Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin lymphoma characterized by the t(11;14)(q13;q32) translocation leading to the overexpression of cyclin D1. EXPERIMENTAL DESIGN: Assays for cytotoxicty including mathematical analysis for synergism, flow-cytometry, immunoblottings, and a xenograft severe combined immunodeficient beige mouse model were used to explore the in vitro and in vivo activity of romidepsin and/or belinostat alone or in combination with the proteasome inhibitor bortezomib in MCL...
January 15, 2010: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Luca Paoluzzi, Luigi Scotto, Enrica Marchi, Venkatraman E Seshan, Owen A O'Connor
Cyproheptadine, an inhibitor of the H1 histamine receptors, has recently shown activity in models of leukaemia and myeloma, presumably through inhibition of cyclin-D expression. Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin lymphoma characterized by overexpression of cyclin-D1. We investigated the effect of cyproheptadine alone and in combination with the proteasome inhibitor bortezomib in models of MCL. The combination of these drugs was mathematically synergistic, producing significant reductions in the mitochondrial membrane potential leading to apoptosis...
September 2009: British Journal of Haematology
Xao X Tang, Marjorie E Robinson, Justin S Riceberg, David Y Kim, Bing Kung, Tracy B Titus, Satoshi Hayashi, Alan W Flake, David Carpentieri, Naohiko Ikegaki
PURPOSE AND EXPERIMENTAL DESIGN: Neuroblastoma (NB) is a common pediatric solid tumor that exhibits a striking clinical bipolarity: favorable and unfavorable. Favorable NB genes (EPHB6, EFNB2, EFNB3, NTRK1, and CD44) are genes whose high-level expression predicts favorable NB outcome, and forced expression of these genes inhibits growth of unfavorable NB cells. In this study, we investigated whether favorable NB gene expression could be augmented in unfavorable NB cells by chemical compounds and whether an increased expression of these genes was associated with suppression of NB growth and metastasis...
September 1, 2004: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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