排序方式: 共有36条查询结果,搜索用时 15 毫秒
1.
Sampey BP Vanhoose AM Winfield HM Freemerman AJ Muehlbauer MJ Fueger PT Newgard CB Makowski L 《Obesity (Silver Spring, Md.)》2011,19(6):1109-1117
Obesity has reached epidemic proportions worldwide and reports estimate that American children consume up to 25% of calories from snacks. Several animal models of obesity exist, but studies are lacking that compare high-fat diets (HFD) traditionally used in rodent models of diet-induced obesity (DIO) to diets consisting of food regularly consumed by humans, including high-salt, high-fat, low-fiber, energy dense foods such as cookies, chips, and processed meats. To investigate the obesogenic and inflammatory consequences of a cafeteria diet (CAF) compared to a lard-based 45% HFD in rodent models, male Wistar rats were fed HFD, CAF or chow control diets for 15 weeks. Body weight increased dramatically and remained significantly elevated in CAF-fed rats compared to all other diets. Glucose- and insulin-tolerance tests revealed that hyperinsulinemia, hyperglycemia, and glucose intolerance were exaggerated in the CAF-fed rats compared to controls and HFD-fed rats. It is well-established that macrophages infiltrate metabolic tissues at the onset of weight gain and directly contribute to inflammation, insulin resistance, and obesity. Although both high fat diets resulted in increased adiposity and hepatosteatosis, CAF-fed rats displayed remarkable inflammation in white fat, brown fat and liver compared to HFD and controls. In sum, the CAF provided a robust model of human metabolic syndrome compared to traditional lard-based HFD, creating a phenotype of exaggerated obesity with glucose intolerance and inflammation. This model provides a unique platform to study the biochemical, genomic and physiological mechanisms of obesity and obesity-related disease states that are pandemic in western civilization today. 相似文献
2.
Shearer J Fueger PT Rottman JN Bracy DP Binas B Wasserman DH 《American journal of physiology. Endocrinology and metabolism》2005,288(2):E292-E297
The role of heart-type cytosolic fatty acid-binding protein (H-FABP) in mediating whole body and muscle-specific long-chain fatty acid (LCFA) and glucose utilization was examined using exercise as a phenotyping tool. Catheters were chronically implanted in a carotid artery and jugular vein of wild-type (WT, n = 8), heterozygous (H-FABP(+/-), n = 8), and null (H-FABP(-/-), n = 7) chow-fed C57BL/6J mice, and mice were allowed to recover for 7 days. After a 5-h fast, conscious, unrestrained mice were studied during 30 min of treadmill exercise (0.6 mph). A bolus of [(125)I]-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid and 2-deoxy-[(3)H]glucose was administered to obtain rates of whole body metabolic clearance (MCR) and indexes of muscle LCFA (R(f)) and glucose (R(g)) utilization. Fasting, nonesterified fatty acids (mM) were elevated in H-FABP(-/-) mice (2.2 +/- 0.9 vs. 1.3 +/- 0.1 and 1.3 +/- 0.2 for WT and H-FABP(+/-)). During exercise, blood glucose (mM) increased in WT (11.7 +/- 0.8) and H-FABP(+/-) (12.6 +/- 0.9) mice, whereas H-FABP(-/-) mice developed overt hypoglycemia (4.8 +/- 0.8). Examination of tissue-specific and whole body glucose and LCFA utilization demonstrated a dependency on H-FABP with exercise in all tissues examined. Reductions in H-FABP led to decreasing exercise-stimulated R(f) and increasing R(g) with the most pronounced effects in heart and soleus muscle. Similar results were seen for MCR with decreasing LCFA and increasing glucose clearance with declining levels of H-FABP. These results show that, in vivo, H-FABP has reciprocal effects on glucose and LCFA utilization and whole body fuel homeostasis when metabolic demands are elevated by exercise. 相似文献
3.
4.
Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer 总被引:18,自引:0,他引:18
Thomas GV Tran C Mellinghoff IK Welsbie DS Chan E Fueger B Czernin J Sawyers CL 《Nature medicine》2006,12(1):122-127
Inhibitors of the kinase mammalian target of rapamycin (mTOR) have shown sporadic activity in cancer trials, leading to confusion about the appropriate clinical setting for their use. Here we show that loss of the Von Hippel-Lindau tumor suppressor gene (VHL) sensitizes kidney cancer cells to the mTOR inhibitor CCI-779 in vitro and in mouse models. Growth arrest caused by CCI-779 correlates with a block in translation of mRNA encoding hypoxia-inducible factor (HIF1A), and is rescued by expression of a VHL-resistant HIF1A cDNA lacking the 5' untranslated region. VHL-deficient tumors show increased uptake of the positron emission tomography (PET) tracer fluorodeoxyglucose (FDG) in an mTOR-dependent manner. Our findings provide preclinical rationale for prospective, biomarker-driven clinical studies of mTOR inhibitors in kidney cancer and suggest that FDG-PET scans may have use as a pharmacodynamic marker in this setting. 相似文献
5.
Fueger PT Hess HS Posey KA Bracy DP Pencek RR Charron MJ Wasserman DH 《The Journal of biological chemistry》2004,279(49):50956-50961
Previous work suggests that normal GLUT4 content is sufficient for increases in muscle glucose uptake (MGU) during exercise because GLUT4 overexpression does not increase exercise-stimulated MGU. Instead of glucose transport, glucose phosphorylation is a primary limitation of exercise-stimulated MGU. It was hypothesized that a partial ablation of GLUT4 would not impair exercise-stimulated MGU when glucose phosphorylation capacity is normal but would do so when glucose phosphorylation capacity was increased. Thus, C57BL/6J mice with hexokinase II (HKII) overexpression (HK(Tg)), a GLUT4 partial knock-out (G4(+/-)), or both (HK(Tg) + G4(+/-)) and wild-type (WT) littermates were implanted with carotid artery and jugular vein catheters for sampling and infusions at 4 months of age. After a 7-day recovery, 5-h fasted mice remained sedentary or ran on a treadmill at 0.6 mph for 30 min (n = 9-12 per group) and received a bolus of 2-deoxy[3H]glucose to provide an index of MGU (Rg). Arterial blood glucose and plasma insulin concentrations were similar in WT, G4(+/-), HKTg, and HKTg + G4(+/-) mice. Sedentary Rg values were the same in all genotypes in all muscles studied, confirming that glucose transport is a significant barrier to basal glucose uptake. Gastrocnemius and soleus Rg were greater in exercising compared with sedentary mice in all genotypes. During exercise, G4(+/-) mice had a marked increase in blood glucose that was corrected by the addition of HK II overexpression. Exercise Rg (micromol/100g/min) was not different between WT and G4(+/-) mice in the gastrocnemius (24 +/- 5 versus 21 +/- 2) or the soleus (54 +/- 6 versus 70 +/- 7). In contrast, the enhanced exercise Rg observed in HKTg mice compared with that in WT mice was absent in HKTg + G4(+/-) mice in both the gastrocnemius (39 +/- 7 versus 22 +/- 6) and the soleus (98 +/- 13 versus 65 +/- 13). Thus, glucose transport is not a significant barrier to exercise-stimulated MGU despite a 50% reduction in GLUT4 content when glucose phosphorylation capacity is normal. However, when glucose phosphorylation capacity is increased by HK II overexpression, GLUT4 availability becomes a marked limitation to exercise-stimulated MGU. 相似文献
6.
7.
Paul REL Lafond T Müller-Graf CDM Nithiuthai S Brey PT Koella JC 《BMC evolutionary biology》2004,4(1):1-13
Background
Theoretical studies suggest that direct and indirect selection have the potential to cause substantial evolutionary change in female mate choice. Similarly, sexual selection is considered a strong force in the evolution of male attractiveness and the exaggeration of secondary sexual traits. Few studies have, however, directly tested how female mate choice and male attractiveness respond to selection. Here we report the results of a selection experiment in which we selected directly on female mating preference for attractive males and, independently, on male attractiveness in the guppy, Poecilia reticulata. We measured the direct and correlated responses of female mate choice and male attractiveness to selection and the correlated responses of male ornamental traits, female fecundity and adult male and female survival.Results
Surprisingly, neither female mate choice nor male attractiveness responded significantly to direct or to indirect selection. Fecundity did differ significantly among lines in a way that suggests a possible sexually-antagonistic cost to male attractiveness.Conclusions
The opportunity for evolutionary change in female mate choice and male attractiveness may be much smaller than predicted by current theory, and may thus have important consequences for how we understand the evolution of female mate choice and male attractiveness. We discuss a number of factors that may have constrained the response of female choice and male attractiveness to selection, including low heritabilities, low levels of genetic (co)variation in the multivariate direction of selection, sexually-antagonistic constraint on sexual selection and the "environmental covariance hypothesis".8.
Alexis Llewellyn Craig Whittington Gavin Stewart Julian PT Higgins Nick Meader 《PloS one》2015,10(12)
Background
The grades of recommendation, assessment, development and evaluation (GRADE) approach is widely implemented in systematic reviews, health technology assessment and guideline development organisations throughout the world. We have previously reported on the development of the Semi-Automated Quality Assessment Tool (SAQAT), which enables a semi-automated validity assessment based on GRADE criteria. The main advantage to our approach is the potential to improve inter-rater agreement of GRADE assessments particularly when used by less experienced researchers, because such judgements can be complex and challenging to apply without training. This is the first study examining the inter-rater agreement of the SAQAT.Methods
We conducted two studies to compare: a) the inter-rater agreement of two researchers using the SAQAT independently on 28 meta-analyses and b) the inter-rater agreement between a researcher using the SAQAT (who had no experience of using GRADE) and an experienced member of the GRADE working group conducting a standard GRADE assessment on 15 meta-analyses.Results
There was substantial agreement between independent researchers using the Quality Assessment Tool for all domains (for example, overall GRADE rating: weighted kappa 0.79; 95% CI 0.65 to 0.93). Comparison between the SAQAT and a standard GRADE assessment suggested that inconsistency was parameterised too conservatively by the SAQAT. Therefore the tool was amended. Following amendment we found fair-to-moderate agreement between the standard GRADE assessment and the SAQAT (for example, overall GRADE rating: weighted kappa 0.35; 95% CI 0.09 to 0.87).Conclusions
Despite a need for further research, the SAQAT may aid consistent application of GRADE, particularly by less experienced researchers. 相似文献9.
Suzanne Arends Marianne Hofman Yvo PT Kamsma Eveline van der Veer Pieternella M Houtman Cees GM Kallenberg Anneke Spoorenberg Elisabeth Brouwer 《Arthritis research & therapy》2013,15(4):R99
Introduction
The aim of this study was to investigate the construct validity and test-retest reliability of the International Physical Activity Questionnaire (IPAQ; long form) and the Short QUestionnaire to Assess Health-enhancing physical activity (SQUASH) and to investigate the relation between daily physical activity and clinical assessments in patients with ankylosing spondylitis (AS).Methods
For validity, the self-report questionnaires IPAQ and SQUASH were compared with daily physical activity assessed with the ActiGraph accelerometer during 7 consecutive days in 63 AS outpatients. For reliability, the IPAQ and SQUASH were administered twice approximately 1 week apart in 52 AS outpatients. In all 115 patients, clinical assessments were performed at the outpatient clinic.Results
IPAQ and SQUASH total scores correlated significantly with accelerometer outcome: ρ = 0.38 and r = 0.35, respectively. Intraclass correlation coefficients between first and second assessments of the IPAQ and SQUASH were 0.83 and 0.89, respectively. Bland-Altman analyses showed no systemic bias, but in particular for the IPAQ the 95% limits of agreement were wide. Daily physical activity assessed by accelerometer, IPAQ, and SQUASH correlated significantly with disease activity, physical activity, and quality of life. A relation with spinal mobility was found only for the accelerometer and SQUASH. The direction of these correlations indicates that higher daily physical activity is related to lower disease activity and better physical function, spinal mobility and quality of life.Conclusions
Both physical activity questionnaires showed modest construct validity. The SQUASH showed good test-retest reliability, superior to the IPAQ. These results indicate that the SQUASH is more suitable than the IPAQ to assess daily physical activity in AS population studies. However, it is desirable to add questions on AS-specific physical activity. Further studies are needed to investigate the causality of the relation between daily physical activity and clinical assessments. 相似文献10.
Steven PT Hooton Andrew R Timms Joanna Rowsell Ray Wilson Ian F Connerton 《Virology journal》2011,8(1):1-14