The Experts below are selected from a list of 15 Experts worldwide ranked by ideXlab platform
Christopher C. T. Smith - One of the best experts on this subject based on the ideXlab platform.
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The Cardioprotective Actions of Leptin Are Lost in the Zucker Obese (fa/fa) Rat
Journal of cardiovascular pharmacology, 2009Co-Authors: Richard A. Dixon, Sean M. Davidson, Abigail M. Wynne, Derek M. Yellon, Christopher C. T. SmithAbstract:Protection against myocardial ischemia-reperfusion injury, including that induced by leptin, involves activation of the reperfusion injury salvage kinase pathway and inhibition of the mitochondrial permeability transition pore. In the current study, we explored the mechanisms underlying leptin-induced cardioprotection further with reference to the leptin receptor (OB-R) and obesity. We examined hearts from Wistar and Zucker Lean Rats that express functional OB-R and Zucker obese (fa/fa) Rats with nonfunctional OB-R. In Langendorff experiments, leptin (10 nM) caused significant reductions in infarct size in hearts from Wistar (leptin treated, 32.4% +/- 3.9% vs. control, 53.2% +/- 3.2%, P < 0.01) and Zucker Lean animals (leptin treated, 25.2% +/- 3.7% vs. control, 53.9% +/- 11.3%, P < 0.01). By contrast, hearts from (fa/fa) did not exhibit significant decreases in infarct size. Leptin increased p44 and p42 phosphorylation in Wistar Rat hearts by 103.9% (P < 0.05) and 157.3% (P < 0.001), respectively, and by 97.0% (P < 0.05) and 158.1% (P < 0.05) in hearts from Zucker Lean Rats. Akt/serine-473 phosphorylation was increased in Wistar hearts by 96.7% (P < 0.05), whereas Akt/threonine-308 phosphorylation was elevated by 43.9% (P < 0.05) in Zucker Lean Rat hearts. Leptin did not influence Akt or p44/42 phosphorylation in (fa/fa) animals. On leptin treatment, mitochondrial permeability transition pore opening was delayed by 43% (P < 0.01) and 30.9% (P < 0.01), respectively, in cardiomyocytes from Wistar and Zucker Lean Rat hearts but not in cardiomyocytes from (fa/fa). This study provides the first evidence that myocardial sensitivity to the tissue preserving actions of leptin is influenced by adiposity and OB-R status.
Richard A. Dixon - One of the best experts on this subject based on the ideXlab platform.
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The Cardioprotective Actions of Leptin Are Lost in the Zucker Obese (fa/fa) Rat
Journal of cardiovascular pharmacology, 2009Co-Authors: Richard A. Dixon, Sean M. Davidson, Abigail M. Wynne, Derek M. Yellon, Christopher C. T. SmithAbstract:Protection against myocardial ischemia-reperfusion injury, including that induced by leptin, involves activation of the reperfusion injury salvage kinase pathway and inhibition of the mitochondrial permeability transition pore. In the current study, we explored the mechanisms underlying leptin-induced cardioprotection further with reference to the leptin receptor (OB-R) and obesity. We examined hearts from Wistar and Zucker Lean Rats that express functional OB-R and Zucker obese (fa/fa) Rats with nonfunctional OB-R. In Langendorff experiments, leptin (10 nM) caused significant reductions in infarct size in hearts from Wistar (leptin treated, 32.4% +/- 3.9% vs. control, 53.2% +/- 3.2%, P < 0.01) and Zucker Lean animals (leptin treated, 25.2% +/- 3.7% vs. control, 53.9% +/- 11.3%, P < 0.01). By contrast, hearts from (fa/fa) did not exhibit significant decreases in infarct size. Leptin increased p44 and p42 phosphorylation in Wistar Rat hearts by 103.9% (P < 0.05) and 157.3% (P < 0.001), respectively, and by 97.0% (P < 0.05) and 158.1% (P < 0.05) in hearts from Zucker Lean Rats. Akt/serine-473 phosphorylation was increased in Wistar hearts by 96.7% (P < 0.05), whereas Akt/threonine-308 phosphorylation was elevated by 43.9% (P < 0.05) in Zucker Lean Rat hearts. Leptin did not influence Akt or p44/42 phosphorylation in (fa/fa) animals. On leptin treatment, mitochondrial permeability transition pore opening was delayed by 43% (P < 0.01) and 30.9% (P < 0.01), respectively, in cardiomyocytes from Wistar and Zucker Lean Rat hearts but not in cardiomyocytes from (fa/fa). This study provides the first evidence that myocardial sensitivity to the tissue preserving actions of leptin is influenced by adiposity and OB-R status.
Xiaoxi Qiao - One of the best experts on this subject based on the ideXlab platform.
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Dietary fat up-regulates the apolipoprotein E mRNA level in the Zucker Lean Rat brain.
Neuroreport, 2001Co-Authors: David S. Knight, Damodar K. Mahajan, Xiaoxi QiaoAbstract:High-fat diet alters apo E-dependent processing of beta-amyloid precursor protein. Here we have evaluated the effects of dietary fat on brain apo E mRNA in Zucker Lean and obese Rats. After approximately 2 months on a high-fat diet, there was significant up-regulation of brain apo E mRNA in the Zucker Lean Rat in parallel with weight gain. Densitometric quantification revealed a 17% increase in apo E mRNA in the brains of Lean Rats fed high-fat diet compared with those of Lean Rats fed Rat chow. No significant difference in brain apo E mRNA of Zucker obese Rats fed different diets was found. These results suggest that dietary fat alters brain apo E levels, which may be regulated, in part, through the leptin receptor.
Didier Laurent - One of the best experts on this subject based on the ideXlab platform.
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Age and muscle-type modulated role of intramyocellular lipids in the progression of insulin resistance in nondiabetic Zucker Rats
Metabolism: clinical and experimental, 2005Co-Authors: Marion Korach-andré, John S. Gounarides, Richard Deacon, Michael E. Beil, Dongming Sun, Jiaping Gao, Didier LaurentAbstract:The effect of muscle fiber type and matuRation on intramyocellular lipid (IMCL) content and its relationship to insulin resistance was investigated. Intramyocellular lipid content in slow-twitch (soleus) and fast-twitch (tibialis anterior, TA) muscles of fa/fa (Zucker fatty Rat, ZFR) and age-matched Lean (Zucker Lean Rat, ZLR) Zucker Rats were repeatedly measured over 3 months. Intramyocellular lipid levels in both the soleus and the TA were significantly higher in the ZFR relative to the ZLR. For the ZFR, IMCLTA increased by ~2-fold from 5.3 to 8.4 weeks of age. No subsequent accumulation of IMCLTA occurred in ZFR from 8.4 up to 13.1 weeks of age. For ZLR, IMCLTA contents steadily decreased from 6.6 to 13.1 weeks of age (−77%, P < .05). In contrast, IMCL levels in the soleus were not significantly altered in either Rat strain over the course of the study. Maximum impairment in whole-body insulin sensitivity in ZFR was observed at 9-weeks of age, concomitant with peak IMCLTA accumulation. Insulin-stimulated 2-deoxy-d-glucose (2DG) transport in the TA muscle of 10.2- and 14.1-week-old ZFR was significantly impaired relative to age-matched ZLR. Insulin-stimulated glucose uptake in the soleus of ZFR and ZLR decreased (P < .05) as the animals matured (ZFR, −49%; ZLR, −69%). Overall, these results support the hypothesis that fast-twitch glycolytic muscles play a major role during the onset of insulin resistance. In addition, proper timing may govern the success of a pharmacological studies aimed at measuring the impact of insulin-sensitizing drugs on IMCL.
Ulrich Wenzel - One of the best experts on this subject based on the ideXlab platform.
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Differential impact of diabetes mellitus type II and arterial hypertension on collateral artery growth and concomitant macrophage accumulation.
VASA. Zeitschrift fur Gefasskrankheiten, 2015Co-Authors: Wulf D. Ito, Natalie Lund, Hendrik Sager, Wiebke Becker, Ulrich WenzelAbstract:Background: Diabetes mellitus type II and arterial hypertension are major risk factors for peripheral arterial disease and have been considered to reduce collateral growth (arteriogenesis). Collateral growth proceeds through different stages. Vascular prolifeRation and macrophage accumulation are hallmarks of early collateral growth. Material and methods: We here compare the impact of arterial hypertension and diabetes mellitus type II on collateral prolifeRation (Brdu incorpoRation) and macrophage accumulation (ED 2 staining) as well as collateral vessel function (collateral conductance) in a Rat model of peripheral vascular disease (femoral artery occlusion), diabetes mellitus type II (Zucker fatty diabetic Rats and Zucker Lean Rat controls) and arterial hypertension (induced via clip placement around the right renal arteriy). We furthermore tested the impact of monocyte chemoattractant protein-1 (MCP‑1) on collateral prolifeRation and macrophage accumulation in these models Results: Diabetic animals sh...
