Abstract:
BACKGROUND:Recent studies suggest that the oxygen-sensing pathway consisting of transcription factor hypoxia-inducible factor and prolyl hydroxylase domain proteins (PHDs) plays a critical role in glucose metabolism. However, the role of adipocyte PHD in the development of obesity has not been clarified. We examined whether deletion of PHD2, the main oxygen sensor, in adipocytes affects diet-induced obesity and associated metabolic abnormalities. METHODS AND RESULTS:To delete PHD2 in adipocyte, PHD2-floxed mice were crossed with aP2-Cre transgenic mice (Phd2(f/f)/aP2-Cre). Phd2(f/f)/aP2-Cre mice were resistant to high-fat diet-induced obesity (36.7±1.7 versus 44.3±2.0 g in control; P<0.01) and showed better glucose tolerance and homeostasis model assessment-insulin resistance index than control mice (3.6±1.0 versus 11.1±2.1; P<0.01). The weight of white adipose tissue was lighter (epididymal fat, 758±35 versus 1208±507 mg in control; P<0.01) with a reduction in adipocyte size. Macrophage infiltration into white adipose tissue was also alleviated in Phd2(f/f)/aP2-Cre mice. Target genes of hypoxia-inducible factor, including glycolytic enzymes and adiponectin, were upregulated in adipocytes of Phd2(f/f)/aP2-Cre mice. Lipid content was decreased and uncoupling protein-1 expression was increased in brown adipose tissue of Phd2(f/f)/aP2-Cre mice. Knockdown of PHD2 in 3T3L1 adipocytes induced a decrease in the glucose level and an increase in the lactate level in the supernatant with upregulation of glycolytic enzymes and reduced lipid accumulation. CONCLUSIONS:PHD2 in adipose tissue plays a critical role in the development of diet-induced obesity and glucose intolerance. PHD2 might be a novel target molecule for the treatment of obesity and associated metabolic abnormalities.
journal_name
Circulationjournal_title
Circulationauthors
Matsuura H,Ichiki T,Inoue E,Nomura M,Miyazaki R,Hashimoto T,Ikeda J,Takayanagi R,Fong GH,Sunagawa Kdoi
10.1161/CIRCULATIONAHA.113.001742subject
Has Abstractpub_date
2013-05-28 00:00:00pages
2078-87issue
21eissn
0009-7322issn
1524-4539pii
CIRCULATIONAHA.113.001742journal_volume
127pub_type
杂志文章相关文献
CIRCULATION文献大全abstract:BACKGROUND:The clinical efficacy of alcohol septal ablation for drug-refractory hypertrophic cardiomyopathy remains unclear. This study examines the outcome of alcohol septal ablation performed at a tertiary hypertrophic cardiomyopathy referral center. METHODS AND RESULTS:Among 601 patients with severely symptomatic o...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.107.738740
更新日期:2008-07-08 00:00:00
abstract:BACKGROUND:Myocardial necrosis can occur during percutaneous coronary intervention (PCI) despite optimal adjunctive pharmacology and careful technique. We investigated the mechanisms of procedural infarction using angiographic analysis, intravascular ultrasound, and delayed-enhancement magnetic resonance imaging. METH...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/CIRCULATIONAHA.105.593210
更新日期:2006-08-15 00:00:00
abstract::Mitral valve closure during cardiopulmonary resuscitation may result from direct cardiac compression. An alternative hypothesis is that with a rise in intrathoracic pressure, mitral valve closure can occur but may be influenced by whether the lungs are inflated or deflated. To test this hypothesis, we placed a large-b...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.78.3.754
更新日期:1988-09-01 00:00:00
abstract::A case history of a 46-year-old Negro male was presented with rheumatic aortic insufficiency, angina pectoris, and possible subacute bacterial endocarditis. While hospitalized, the patient developed angina pectoris associated with micturition. This was not accompanied by a change in blood pressure, pulse, or increase ...
journal_title:Circulation
pub_type: 历史文章,杂志文章
doi:10.1161/01.cir.27.1.85
更新日期:1963-01-01 00:00:00
abstract::This is a report of a 10-year-old child who underwent surgery for complex congenital heart disease consisting of corrected transposition of the great vessels, ventricular septal defect, patent ductus arterisus, severe left-sided atrioventricular (AV) valve insuffieicney (Ebstein's deformity) and Wolff-Parkinson-White ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.61.6.1256
更新日期:1980-06-01 00:00:00
abstract:BACKGROUND:Healthy levels of lifestyle factors can reduce the risk of cardiovascular disease. However, except for smoking status, often considered a traditional risk factor, their effect on cardiovascular risk prediction is unclear. METHODS AND RESULTS:We used a case-cohort design of postmenopausal nonsmokers in the m...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.114.012069
更新日期:2014-10-21 00:00:00
abstract:BACKGROUND:Clinical detection of transplant rejection by repeated endomyocardial biopsy requires catheterization and entails risks. Recently developed molecular and cellular imaging techniques that visualize macrophage host responses could provide a noninvasive alternative. Yet, which macrophage functions may provide u...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.108.796888
更新日期:2009-04-14 00:00:00
abstract:BACKGROUND:Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute corona...
journal_title:Circulation
pub_type: 杂志文章,meta分析,评审
doi:10.1161/CIR.0000000000000019
更新日期:2014-03-25 00:00:00
abstract:BACKGROUND AND PURPOSE:The guidelines presented in this consensus statement are intended to serve researchers, clinicians, reviewers, and regulators in the selection of the most appropriate primary outcome for a clinical trial of cardiac arrest therapies. The American Heart Association guidelines for the treatment of c...
journal_title:Circulation
pub_type: 杂志文章,实务指引
doi:10.1161/CIR.0b013e3182340239
更新日期:2011-11-08 00:00:00
abstract::An experiment was designed to determine optimal methods of myocardial reperfusion after normothermic ischemic arrest in the in vivo pig heart. Four variables were studied: 1) ischemic arrest for 15 minutes repeated six times vs 30 minutes repeated three times: 2) coronary reperfusion between each arrest period lasting...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract:BACKGROUND:Abnormal vascular reactivity represents a fundamental disturbance in vascular biology with the development of atherosclerosis. Because endothelial vasodilator function plays a pivotal role in controlling vasomotor tone, we hypothesized that atherosclerotic wall thickening might directly interfere with defici...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.89.6.2525
更新日期:1994-06-01 00:00:00
abstract::The electrophysiologic effects of intravenously administered disopyramide (2 mg/kg) on three parameters of sinus node function were examined in 16 symptomatic patients with sinus node dysfunction. Based on their ECG data before study, patients were subdivided into group A (n = 8), those with sinus pauses and/or sinoat...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.59.2.226
更新日期:1979-02-01 00:00:00
abstract::Cerebral neurons can tolerate at least 20 min of normothermic ischemic anoxia. Cerebral recovery from more than 5 min of cardiac arrest is hampered by complex secondary derangements of multiple organ systems after reperfusion. There is increasing support of our hypothesis that this "postresuscitation syndrome" include...
journal_title:Circulation
pub_type: 杂志文章,评审
doi:
更新日期:1986-12-01 00:00:00
abstract:BACKGROUND:A key component of reperfusion of myocardial infarction is an immediate inflammatory response, which enhances tissue repair. Matrix turnover is crucial to tissue repair, and matrix metalloproteinases (MMPs) are key enzymes involved in matrix degradation. The hypothesis tested is that one inflammation-based e...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.103.17.2181
更新日期:2001-05-01 00:00:00
abstract::The electrophysiologic mechanisms for the initiation and termination of re-entrant ventricular arrhythmias (RVA) were critically analyzed in dogs 3-7 days following ligation of the anterior descending coronary artery, utilizing direct recordings of the re-entrant pathway (RP) from the epicardial surface of the infarct...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.55.5.702
更新日期:1977-05-01 00:00:00
abstract:BACKGROUND:Since 1990, sternotomy has been the preferred approach for construction of a modified Blalock-Taussig shunt (MBTS) at Children's Hospital, Boston, Mass. In retrospect, we sought to test the hypothesis that this approach yields less mortality and morbidity than the traditional thoracotomy approach. METHODS A...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.92.9.256
更新日期:1995-11-01 00:00:00
abstract:BACKGROUND:Patients with bicuspid aortic valve (AV) stenosis were excluded from the pivotal evaluations of transcatheter AV replacement (TAVR) devices. We sought to evaluate the outcomes of TAVR in patients with bicuspid AV stenosis in comparison with those with tricuspid AV stenosis. METHODS:We used data from the Soc...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.119.040333
更新日期:2020-03-31 00:00:00
abstract:BACKGROUND:There are no reported studies on the safety and efficacy of low-dose aspirin with low-intensity oral anticoagulation in patients with heart valve replacement. In this study, we compared the use of 100 mg/d aspirin with 650 mg/d aspirin in the prevention of systemic embolism and vascular death in patients wit...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.94.9.2113
更新日期:1996-11-01 00:00:00
abstract:BACKGROUND:Conflicting results from recent observational studies have raised questions concerning the benefit of β-blockers for patients undergoing coronary artery bypass grafting (CABG). Furthermore, the efficacy of long-term β-blocker therapy in CABG patients after hospital discharge is uncertain. METHODS AND RESULT...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.114.014209
更新日期:2015-06-23 00:00:00
abstract::Two-dimensional echocardiography can provide serial cross-sectional images of the left ventricular cavity. We examined whether such serial images from steady-state ejecting hearts would allow three-dimensional reconstruction and accurate volume estimation without major geometric assumptions. Cross-circulated, paced do...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.60.2.320
更新日期:1979-08-01 00:00:00
abstract:BACKGROUND:During heart development, the ventricular activation sequence changes from a base-to-apex to an apex-to-base pattern. We investigated the possibility of impulse propagation through remnants of atrioventricular (AV) connections in quail hearts. METHODS AND RESULTS:In 86 hearts (group A, HH30-34, n=15; group ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.106.658807
更新日期:2007-01-02 00:00:00
abstract::We have compared casual indirect measurements of arterial pressure obtained 1) by the general practitioner (GP) and 2) in the outpatient clinic (OPC) with 24 hour continuous recording of direct arterial pressure in two selected group of unrestricted patients. 1) Eight asymptomatic, untreated patients with suspected hy...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.51.6.1101
更新日期:1975-06-01 00:00:00
abstract:BACKGROUND:The American Heart Association Cardiovascular Health score (CVH score) is inversely associated with cardiovascular disease (CVD) incidence, but the mechanisms underlying this association warrant exploration. METHODS AND RESULTS:We related the CVH score to circulating biomarkers and prevalent subclinical CVD...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.114.009273
更新日期:2014-11-04 00:00:00
abstract::A genetic-epidemiologic study was undertaken of a white Colorado population of 207 patients who had a myocardial infarction before age 55 years. Nineteen independent variables were compared between the 207 cases and 621 controls, matched 3:1. The highest risk ratios were associated with a positive family history for i...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.61.3.503
更新日期:1980-03-01 00:00:00
abstract:BACKGROUND:An inverse association between height and risk of coronary heart disease (CHD) has been reported in several case-control and cohort studies, but the reasons for the association remain uncertain. We evaluated this association among 22,071 male physicians, a population homogeneous for high educational attainme...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.88.4.1437
更新日期:1993-10-01 00:00:00
abstract:BACKGROUND:Adenosine receptor activation has been proposed to explain the cardioprotective effect of ischemic preconditioning in rabbit hearts. We tested this hypothesis in a rat model by assessing whether administration of an adenosine antagonist could block the protective effect of preconditioning and whether adenosi...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.87.5.1642
更新日期:1993-05-01 00:00:00
abstract:BACKGROUND:Impaired endothelium-dependent, nitric oxide (NO)-mediated vasodilation may contribute to increased vasomotor tone in patients with heart failure. Whether decreased endothelium-dependent, NO-mediated vasodilation in patients with heart failure is due to decreased synthesis or increased degradation of NO is u...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.99.16.2113
更新日期:1999-04-27 00:00:00
abstract::The amplitude and distribution of epicardial ST-segment elevation (ST) were examined for an 8-hour period after coronary occlusion in eight baboons and five pigs. ST was determined from unipolar epicardial electrograms obtained from a high-resolution matrix of fixed electrodes overlying a transmural region of ischemia...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.60.4.930
更新日期:1979-10-01 00:00:00
abstract:BACKGROUND:To date, the uptake of drugs into the human heart by transport proteins is poorly understood. A candidate protein is the organic cation transporter novel type 2 (OCTN2) (SLC22A5), physiologically acting as a sodium-dependent transport protein for carnitine. We investigated expression and localization of OCTN...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.586107
更新日期:2006-02-28 00:00:00
abstract::The goals of electrocardiographic (ECG) monitoring in hospital settings have expanded from simple heart rate and basic rhythm determination to the diagnosis of complex arrhythmias, myocardial ischemia, and prolonged QT interval. Whereas computerized arrhythmia analysis is automatic in cardiac monitoring systems, compu...
journal_title:Circulation
pub_type: 指南,杂志文章,实务指引
doi:10.1161/01.CIR.0000145144.56673.59
更新日期:2004-10-26 00:00:00