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Marin L Gantner, Bethany C Hazen, Elodie Eury, Erin L Brown, Anastasia Kralli
Brown adipose tissue (BAT) thermogenesis relies on a high abundance of mitochondria and the unique expression of the mitochondrial protein UCP1, which uncouples substrate oxidation from ATP synthesis. Adrenergic stimulation of brown adipocytes activates UCP1-mediated thermogenesis; it also induces the expression of Ucp1 and other genes important for thermogenesis, thereby endowing adipocytes with higher oxidative and uncoupling capacities. Adipocyte mitochondrial biogenesis and oxidative capacity are controlled by multiple transcription factors, including the estrogen-related receptor α (ERRα)...
October 20, 2016: Endocrinology
Yantao Chen, Kunshui Zhang, Yang Li, Qing He
Osteosarcoma patients often exhibit pulmonary metastasis, which results in high patient mortality. Understanding the mechanisms of advanced metastasis in osteosarcoma cell is important for the targeted treatment and drug development. Our present study revealed that transforming growth factor-β (TGF-β) treatment can significantly promote the in vitro migration and invasion of human osteosarcoma MG-63 and HOS cells. The loss of epithelial characteristics E-cadherin (E-Cad) and up regulation of mesenchymal markers Vimentin (Vim) suggested TGF-β induced epithelial-mesenchymal transition (EMT) of osteosarcoma cells...
August 17, 2016: Cell Adhesion & Migration
Shailaja D Divekar, Deanna M Tiek, Aileen Fernandez, Rebecca B Riggins
Estrogen-related receptors (ERRs) are founding members of the orphan nuclear receptor (ONR) subgroup of the nuclear receptor superfamily. Twenty-seven years of study have yet to identify cognate ligands for the ERRs, though they have firmly placed ERRα and ERRγ at the intersection of cellular metabolism and oncogenesis. The pace of discovery for novel functions of ERRβ, however, has until recently been somewhat slower than that of its family members. ERRβ has also been largely ignored in summaries and perspectives of the ONR literature...
2016: Nuclear Receptor Signaling
Liudi Zhang, Peihong Liu, Haifei Chen, Qunyi Li, Lu Chen, Huijie Qi, Xiaojin Shi, Yongli Du
The estrogen-related receptor α (ERRα) is an orphan nuclear receptor that plays a primary role in the regulation of cellular energy homeostasis and osteogenesis. It is reported that ERRα is widely expressed in a range of tissues and accumulating evidence has supported that the high expression of ERRα correlates with poor prognosis of various human malignancies, including breast, endometrium, colon, prostate and ovary cancers. Herein is described the discovery of a novel selective inverse agonist (HSP1604) of ERRα, but not of ERRβ and ERRγ, as determined using transient transfection luciferase reporter assay and a time-resolved fluorescence resonance energy transfer (TR-FRET) co-activator assay...
October 15, 2016: European Journal of Pharmacology
Saleh Omairi, Antonios Matsakas, Hans Degens, Oliver Kretz, Kenth-Arne Hansson, Andreas Våvang Solbrå, Jo C Bruusgaard, Barbara Joch, Roberta Sartori, Natasa Giallourou, Robert Mitchell, Henry Collins-Hooper, Keith Foster, Arja Pasternack, Olli Ritvos, Marco Sandri, Vihang Narkar, Jonathan R Swann, Tobias B Huber, Ketan Patel
A central tenet of skeletal muscle biology is the existence of an inverse relationship between the oxidative fibre capacity and its size. However, robustness of this relationship is unknown. We show that superimposition of Estrogen-related receptor gamma (Errγ) on the myostatin (Mtn) mouse null background (Mtn(-/-)/Errγ(Tg/+)) results in hypertrophic muscle with a high oxidative capacity thus violating the inverse relationship between fibre size and oxidative capacity. We also examined the canonical view that oxidative muscle phenotype positively correlate with Satellite cell number, the resident stem cells of skeletal muscle...
2016: ELife
Katerina Makarova, Pawel Siudem, Katarzyna Zawada, Justyna Kurkowiak
Bisphenol A (BPA) acts as an endocrine-disrupting compound even at a low concentration. Degradation of BPA could lead to the formation of toxic products. In this study, we compare the toxicity of BPA and seven intermediate products of its degradation. The accuracy of three molecular docking programs (Surflex, Autodock, and Autodock Vina) in predicting the binding affinities of selected compounds to human (ERα, ERβ, and ERRγ) and zebrafish (ERα, ERRγA, and ERRγB) estrogen and estrogen-related receptors was evaluated...
October 2016: Zebrafish
Yoon Seok Jung, Ji-Min Lee, Don-Kyu Kim, Yong-Soo Lee, Ki-Sun Kim, Yong-Hoon Kim, Jina Kim, Myung-Shik Lee, In-Kyu Lee, Seong Heon Kim, Sung Jin Cho, Won-Il Jeong, Chul-Ho Lee, Robert A Harris, Hueng-Sik Choi
BACKGROUND: Fibroblast growth factor 21 (FGF21), a stress inducible hepatokine, is synthesized in the liver and plays important roles in glucose and lipid metabolism. However, the mechanism of hepatic cannabinoid type 1 (CB1) receptor-mediated induction of FGF21 gene expression is largely unknown. RESULTS: Activation of the hepatic CB1 receptor by arachidonyl-2'-chloroethylamide (ACEA), a CB1 receptor selective agonist, significantly increased FGF21 gene expression...
2016: PloS One
Wei Gong, Jing Yu, Qilei Wang, Shuzhen Li, Jiayu Song, Zhanjun Jia, Songming Huang, Aihua Zhang
Accumulating evidence has shown that podocyte apoptosis is of vital importance for the development of glomerulosclerosis and progressive loss of renal function. However, the molecular mechanisms leading to podocyte apoptosis are still elusive. In this study, we investigated the role of estrogen-related receptor (ERR) γ in podocyte apoptosis, as well as the underlying mechanisms. Treatment of PAN caused a dose- and time-dependent podocyte apoptosis in line with a significant downregulation of ERRγ. Interestingly, the occurrence of ERRγ downregulation appeared earlier than the onset of cell apoptosis, suggesting a potential that ERRγ reduction triggered apoptotic response in podocyte...
September 2016: International Journal of Biochemistry & Cell Biology
Jagannath Misra, Don-Kyu Kim, Yoon Seok Jung, Han Byeol Kim, Yong-Hoon Kim, Eun-Kyung Yoo, Byung Gyu Kim, Sunghoon Kim, In-Kyu Lee, Robert A Harris, Jeong-Sun Kim, Chul-Ho Lee, Jin Won Cho, Hueng-Sik Choi
Estrogen-related receptor γ (ERRγ) is a major positive regulator of hepatic gluconeogenesis. Its transcriptional activity is suppressed by phosphorylation signaled by insulin in the fed state, but whether posttranslational modification alters its gluconeogenic activity in the fasted state is not known. Metabolically active hepatocytes direct a small amount of glucose into the hexosamine biosynthetic pathway, leading to protein O-GlcNAcylation. In this study, we demonstrate that ERRγ is O-GlcNAcylated by O-GlcNAc transferase in the fasted state...
October 2016: Diabetes
Xinde Zheng, Leah Boyer, Mingji Jin, Jerome Mertens, Yongsung Kim, Li Ma, Li Ma, Michael Hamm, Fred H Gage, Tony Hunter
How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival...
2016: ELife
Jina Kim, Jungwook Chin, Chun Young Im, Eun Kyung Yoo, Seoyeon Woo, Hee Jong Hwang, Joong-Heui Cho, Kyung-Ah Seo, Jaeyoung Song, Hayoung Hwang, Kyung-Hee Kim, Nam Doo Kim, Suk Kyoon Yoon, Jae-Han Jeon, Seung-Yun Yoon, Yong Hyun Jeon, Hueng-Sik Choi, In-Kyu Lee, Seong Heon Kim, Sung Jin Cho
Estrogen-related receptor gamma (ERRγ) has recently been recognized as an attractive target for treating inflammation, cancer, and metabolic disorders. Herein, we discovered and demonstrated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that could act as highly selective inverse agonists for ERRγ. The results were comparable to those for GSK5182 (4), a leading ERRγ inverse agonist ligand. Briefly, the half-maximal inhibitory concentration (IC50) range of the synthesized compounds for ERRγ was 0...
September 14, 2016: European Journal of Medicinal Chemistry
Peng Chen, Haibin Wang, Fan Yang, Hongwu Chen, Wei He, Junjian Wang
Curcumin has demonstrated valuable therapeutic potential against a variety of human cancers including osteosarcoma. However, the molecular mechanisms underlying its anti-tumor effect remain to be poorly understood. By RNA sequence profiling, we found that curcumin significantly down-regulates the expression of estrogen-related receptor alpha (ERRα) in osteosarcoma cells. Overexpression of ERRα diminished curcumin-activated apoptotic cell death and scavenged curcumin-induced reactive oxygen species (ROS), while ERRα silencing sensitized osteosarcoma cells to curcumin, resulting in increased inhibition of cell proliferation...
May 27, 2016: Journal of Cellular Biochemistry
Violaine Tribollet, Bruno Barenton, Auriane Kroiss, Séverine Vincent, Ling Zhang, Christelle Forcet, Catherine Cerutti, Séverine Périan, Nathalie Allioli, Jacques Samarut, Jean-Marc Vanacker
MicroRNA-135a (miR-135a) down-modulates parameters of cancer progression and its expression is decreased in metastatic breast cancers (as compared to non-metastatic tumors) as well as in prostate tumors relative to normal tissue. These expression and activity patterns are opposite to those of the Estrogen-Related Receptor α (ERRα), an orphan member of the nuclear receptor family. Indeed high expression of ERRα correlates with poor prognosis in breast and prostate cancers, and the receptor promotes various traits of cancer aggressiveness including cell invasion...
2016: PloS One
Kuo-Feng Chiang, Chien-Ming Cheng, Shih-Chuan Tsai, Wan-Yu Lin, Yu-Cheng Chang, Jin-Long Huang, Guang-Uei Hung, Chia-Hung Kao, Shih-Ann Chen, Pesus Chou, Ji Chen
BACKGROUND: Cardiac resynchronization therapy (CRT) can provide cardiac reverse remodeling (RR), which may include mechanical reverse remodeling (MRR) and/or electrical reverse remodeling (ERR). However, uncoupling of MRR and ERR is not uncommon, and the underlying mechanisms are not clear. This study aimed to evaluate the relationship of myocardial substrate characteristics as assessed by myocardial perfusion imaging (MPI) and cardiac RR post-CRT. MATERIALS AND METHODS: Forty-one patients (26 men, mean age 66 ± 10 years) with heart failure received CRT for at least 12 months were assigned to three groups according to their levels of RR: I, MRR + ERR (ESV reduced ≥15 % and intrinsic QRS duration reduced ≥10 ms); II, MRR only (ESV reduced ≥15 %); and III, non-responder (the others)...
August 2016: Annals of Nuclear Medicine
Pierre-Marie Badin, Isabelle K Vila, Danesh H Sopariwala, Vikas Yadav, Sabina Lorca, Katie Louche, Eun Ran Kim, Qingchun Tong, Min Sup Song, Cedric Moro, Vihang A Narkar
Dissecting exercise-mimicking pathways that can replicate the benefits of exercise in obesity and diabetes may lead to promising treatments for metabolic disorders. Muscle estrogen-related receptor gamma (ERRγ) is induced by exercise, and when over-expressed in the skeletal muscle mimics exercise by stimulating glycolytic-to-oxidative myofiber switch, mitochondrial biogenesis and angiogenesis in lean mice. The objective of this study was to test whether muscle ERRγ in obese mice mitigates weight gain and insulin resistance...
2016: Scientific Reports
Veronica Torrano, Lorea Valcarcel-Jimenez, Ana Rosa Cortazar, Xiaojing Liu, Jelena Urosevic, Mireia Castillo-Martin, Sonia Fernández-Ruiz, Giampaolo Morciano, Alfredo Caro-Maldonado, Marc Guiu, Patricia Zúñiga-García, Mariona Graupera, Anna Bellmunt, Pahini Pandya, Mar Lorente, Natalia Martín-Martín, James David Sutherland, Pilar Sanchez-Mosquera, Laura Bozal-Basterra, Amaia Zabala-Letona, Amaia Arruabarrena-Aristorena, Antonio Berenguer, Nieves Embade, Aitziber Ugalde-Olano, Isabel Lacasa-Viscasillas, Ana Loizaga-Iriarte, Miguel Unda-Urzaiz, Nikolaus Schultz, Ana Maria Aransay, Victoria Sanz-Moreno, Rosa Barrio, Guillermo Velasco, Paolo Pinton, Carlos Cordon-Cardo, Jason W Locasale, Roger R Gomis, Arkaitz Carracedo
Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewiring. Here we show that the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1α (PGC1α) suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1α is downregulated in prostate cancer and associated with disease progression...
June 2016: Nature Cell Biology
Shiyuan Huang, Lu Jin, Jie Shen, Ping Shang, Xianxun Jiang, Xiaotong Wang
Chronic obstructive pulmonary disease can cause muscle fibre transformation due to chronic intermittent hypoxia-hypercapnia (CIHH). Studies have shown that high expression of Sox6 in muscle could suppress type-I fibres through downregulating the PPARβ (peroxisome proliferator-activated receptor β)/ERRγ (oestrogen-related receptor γ)/microRNA pathway. However, whether this pathway is involved in CIHH-induced muscle fibre transformation is unknown. Electrical stimulation (ES) is an effective approach to ameliorate muscle dysfunction...
2016: Scientific Reports
C Salvador Coloma, O M Niño, J Gomez Codina, C Escoin Pérez, S Palanca, D Akhoundova Sanoyan, M Melián, J Montalar, O Juan
No abstract text is available yet for this article.
April 2016: Journal of Thoracic Oncology
Zheqiong Tan, Xiangjian Luo, Lanbo Xiao, Min Tang, Ann M Bode, Zigang Dong, Ya Cao
PGC1α is a transcription factor coactivator that influences a majority of cellular metabolic pathways. Abnormal expression of PGC1α is associated with several chronic diseases and, in recent years, it has been shown to be a critical controller of cancer development. PGC1α acts as a stress sensor in cancer cells and can be activated by nutrient deprivation, oxidative damage, and chemotherapy. It influences mitochondria respiration, reactive oxygen species defense system, and fatty acid metabolism by interacting with specific transcription factors...
May 2016: Molecular Cancer Therapeutics
Silvia Salatino, Barbara Kupr, Mario Baresic, Erik van Nimwegen, Christoph Handschin
The peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) coordinates the transcriptional network response to promote an improved endurance capacity in skeletal muscle, eg, by coactivating the estrogen-related receptor-α (ERRα) in the regulation of oxidative substrate metabolism. Despite a close functional relationship, the interaction between these 2 proteins has not been studied on a genomic level. We now mapped the genome-wide binding of ERRα to DNA in a skeletal muscle cell line with elevated PGC-1α and linked the DNA recruitment to global PGC-1α target gene regulation...
July 2016: Molecular Endocrinology
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