Abstract:
:Recent studies have established the involvement of the fat mass and obesity-associated gene (FTO) in metabolic disorders such as obesity and diabetes. However, the precise molecular mechanism by which FTO regulates metabolism remains unknown. Here, we used a structure-based virtual screening of U.S. Food and Drug Administration-approved drugs to identify entacapone as a potential FTO inhibitor. Using structural and biochemical studies, we showed that entacapone directly bound to FTO and inhibited FTO activity in vitro. Furthermore, entacapone administration reduced body weight and lowered fasting blood glucose concentrations in diet-induced obese mice. We identified the transcription factor forkhead box protein O1 (FOXO1) mRNA as a direct substrate of FTO, and demonstrated that entacapone elicited its effects on gluconeogenesis in the liver and thermogenesis in adipose tissues in mice by acting on an FTO-FOXO1 regulatory axis.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Peng S,Xiao W,Ju D,Sun B,Hou N,Liu Q,Wang Y,Zhao H,Gao C,Zhang S,Cao R,Li P,Huang H,Ma Y,Wang Y,Lai W,Ma Z,Zhang W,Huang S,Wang H,Zhang Z,Zhao L,Cai T,Zhao YL,Wang F,Nie Y,Zhi G,Yang YG,Zhang EE,doi
10.1126/scitranslmed.aau7116subject
Has Abstractpub_date
2019-04-17 00:00:00issue
488eissn
1946-6234issn
1946-6242pii
11/488/eaau7116journal_volume
11pub_type
杂志文章abstract::A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heteroto...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3005271
更新日期:2013-04-24 00:00:00
abstract::As the prevalence of Alzheimer's disease (AD) grows, so do the costs it imposes on society. Scientific, clinical, and financial interests have focused current drug discovery efforts largely on the single biological pathway that leads to amyloid deposition. This effort has resulted in slow progress and disappointing ou...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3008228
更新日期:2014-06-18 00:00:00
abstract::The Point-Person Project, a child-health research initiative, enables rapid response to opportunities for participation in multicenter pediatric clinical trials. ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaa2045
更新日期:2015-03-18 00:00:00
abstract::Gene therapy is emerging as a therapeutic modality for treating disorders of the retina. Photoreceptor cells are the primary cell type affected in many inherited diseases of retinal degeneration. Successfully treating these diseases with gene therapy requires the identification of efficient and safe targeting vectors ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3002103
更新日期:2011-06-22 00:00:00
abstract::Acquired lymphedema is a cancer sequela and a global health problem currently lacking pharmacologic therapy. We have previously demonstrated that ketoprofen, an anti-inflammatory agent with dual 5-lipoxygenase and cyclooxygenase inhibitory properties, effectively reverses histopathology in experimental lymphedema. We ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aal3920
更新日期:2017-05-10 00:00:00
abstract::Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This st...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaz0463
更新日期:2020-06-03 00:00:00
abstract::Overcoming drug resistance and targeting leukemic stem cells (LSCs) remain major challenges in curing BCR-ABL+ human leukemia. Using an advanced drug/proliferation screen, we have uncovered a prosurvival role for protein phosphatase 2A (PP2A) in tyrosine kinase inhibitor (TKI)-insensitive leukemic cells, regulated by ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aan8735
更新日期:2018-02-07 00:00:00
abstract::Migraine-related photophobia is multifaceted and may be mediated by numerous pathways. ...
journal_title:Science translational medicine
pub_type: 评论,杂志文章
doi:10.1126/scitranslmed.aan8206
更新日期:2017-07-12 00:00:00
abstract::Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision thro...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaa8791
更新日期:2015-07-15 00:00:00
abstract::We outline the fundamental properties of a highly participatory rapid learning system that can be developed in part from meaningful use of electronic health records (EHRs). Future widespread adoption of EHRs will make increasing amounts of medical information available in computable form. Secured and trusted use of th...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3001456
更新日期:2010-11-10 00:00:00
abstract::Aggregation of β-amyloid (Aβ) in the brain begins to occur years before the clinical onset of Alzheimer's disease (AD). Before Aβ aggregation, concentrations of extracellular soluble Aβ in the interstitial fluid (ISF) space of the brain, which are regulated by neuronal activity and the sleep-wake cycle, correlate with...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3004291
更新日期:2012-09-05 00:00:00
abstract::Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, are the most widely prescribed medications for diseases involving bone, with nearly 200 million prescriptions written annually. Recently, widespread use of N-BPs has been challenged due to the risk of rare but traumatic side effects such as atypical fem...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aav9166
更新日期:2020-05-20 00:00:00
abstract::The U.S.-Latin America Cancer Research Network strives to expand translational research capabilities and forge new collaborations. ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aad5859
更新日期:2015-12-23 00:00:00
abstract::Accumulating evidence has shown that repeated exposure to general anesthesia during critical stages of brain development results in long-lasting behavioral deficits later in life. To date, there has been no effective treatment to mitigate the neurotoxic effects of anesthesia on brain development. By performing calcium...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaf7151
更新日期:2016-06-22 00:00:00
abstract::Case fatality rates for severe malaria remain high even in the best clinical settings because antimalarial drugs act against the parasite without alleviating life-threatening inflammation. We assessed the potential for host-directed therapy of severe malaria of a new class of anti-inflammatory drugs, the innate defens...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3003515
更新日期:2012-05-23 00:00:00
abstract::Tumor escape from immune-mediated destruction has been associated with immunosuppressive mechanisms that inhibit T cell activation. Although evidence for an active immune response, including infiltration with CD8(+) T cells, can be found in a subset of patients, those tumors are nonetheless not immunologically rejecte...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3006504
更新日期:2013-08-28 00:00:00
abstract::Acquired ESR1 mutations are a major mechanism of resistance to aromatase inhibitors (AIs). We developed ultra high-sensitivity multiplex digital polymerase chain reaction assays for ESR1 mutations in circulating tumor DNA (ctDNA) and investigated the clinical relevance and origin of ESR1 mutations in 171 women with ad...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aac7551
更新日期:2015-11-11 00:00:00
abstract::Merkel cell polyomavirus (MCV) causes ~80% of primary and metastatic Merkel cell carcinomas (MCCs). By comparing digital transcriptome subtraction deep-sequencing profiles, we found that transcripts of the cellular survivin oncoprotein [BIRC5a (baculoviral inhibitor of apoptosis repeat-containing 5)] were up-regulated...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3003713
更新日期:2012-05-09 00:00:00
abstract::High doses of oral vitamin D3 attenuate skin inflammation following experimentally induced sun damage. ...
journal_title:Science translational medicine
pub_type: 评论,杂志文章
doi:10.1126/scitranslmed.aan5233
更新日期:2017-06-14 00:00:00
abstract::Biallelic mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a disease characterized by calcification in the skin, eyes, and blood vessels. The function of ATP-binding cassette C6 (ABCC6) and the pathogenesis of PXE remain unclear. We used mouse models and patient fibroblasts to demonstrate genetic interaction a...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aal1669
更新日期:2017-06-07 00:00:00
abstract::Epidermal growth factor receptor (EGFR) gene mutations (G719X, exon 19 deletions/insertions, L858R, and L861Q) predict favorable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). However, EGFR exon 20 insertion mutations (~10% of all EGFR mutations) are generally assoc...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3007205
更新日期:2013-12-18 00:00:00
abstract::Pathogenic immunoglobulin G (IgG) autoantibodies characterize some human autoimmune diseases; their high concentration and long half-life are dependent on recycling by the neonatal Fc receptor (FcRn). Inhibition of FcRn is an attractive new treatment concept for IgG-mediated autoimmune diseases. Rozanolixizumab (UCB76...
journal_title:Science translational medicine
pub_type: 杂志文章,随机对照试验
doi:10.1126/scitranslmed.aan1208
更新日期:2017-11-01 00:00:00
abstract::Physiologically relevant ALK (anaplastic lymphoma kinase) expression was not detected in human and mouse monocytes and macrophages, suggesting that the effects of bioactive compounds on stimulator of interferon genes (STING) activation may not depend on ALK. ...
journal_title:Science translational medicine
pub_type: 评论,杂志文章
doi:10.1126/scitranslmed.aar4321
更新日期:2018-12-12 00:00:00
abstract::About one-third of people in the developed world will undergo cataract surgery in their lifetime. Although marked improvements in surgical technique have occurred since the development of the current approach to lens replacement in the late 1960s and early 1970s, some critical steps of the procedure can still only be ...
journal_title:Science translational medicine
pub_type: 临床试验,杂志文章
doi:10.1126/scitranslmed.3001305
更新日期:2010-11-17 00:00:00
abstract::Adults with relapsed B cell acute lymphoblastic leukemia (B-ALL) have a dismal prognosis. Only those patients able to achieve a second remission with no minimal residual disease (MRD) have a hope for long-term survival in the context of a subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We ha...
journal_title:Science translational medicine
pub_type: 临床试验,杂志文章
doi:10.1126/scitranslmed.3005930
更新日期:2013-03-20 00:00:00
abstract::Neuroinflammation has been increasingly recognized to play a critical role in Alzheimer's disease (AD). The epoxy fatty acids (EpFAs) are derivatives of the arachidonic acid metabolism pathway and have anti-inflammatory activities. However, their efficacy is limited because of their rapid hydrolysis by the soluble epo...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.abb1206
更新日期:2020-12-09 00:00:00
abstract::Attention deficit hyperactivity disorder (ADHD) is a common and persistent condition characterized by developmentally atypical and impairing inattention, hyperactivity, and impulsiveness. We identified de novo and rare copy number variations (CNVs) in 248 unrelated ADHD patients using million-feature genotyping arrays...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3002464
更新日期:2011-08-10 00:00:00
abstract::Lung cancer is more deadly than colon, breast, and prostate cancers combined, and treatment improvements have failed to improve prognosis significantly. Here, we identify a critical mediator of lung cancer progression, Rac1b, a tumor-associated protein with cell-transforming properties that are linked to the matrix me...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3004062
更新日期:2012-07-11 00:00:00
abstract::Conventional radiation therapy for cancer usually consists of multiple treatments (called fractions) with low doses of radiation. These dose schemes are planned with the guidance of the linear-quadratic (LQ) model, which has been the most prevalent model for designing dose schemes in radiation therapy. The high-dose f...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3000864
更新日期:2010-07-07 00:00:00
abstract::Canavan disease is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to loss of enzyme activity and increased concentrations of the substrate N-acetyl-aspartate (NAA) in the brain. Accumulation of NAA results in spongiform degeneration of white matter and severe impairment of p...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3003454
更新日期:2012-12-19 00:00:00