Serial changes in norepinephrine kinetics associated with feeding dogs a high-fat diet.

Department of Pediatrics, Pediatric Cardiology Division, University of Michigan, Ann Arbor, MI 48109-5204, USA.
Journal of Clinical Hypertension (Impact Factor: 2.96). 02/2010; 12(2):117-24. DOI: 10.1111/j.1751-7176.2009.00230.x
Source: PubMed

ABSTRACT The role of increased sympathetic nervous system (SNS) activity in the pathogenesis of obesity hypertension and insulin resistance is controversial. Eight dogs were instrumented and fed a high-fat diet (HFD) for 6 weeks. Dogs were evaluated for changes in weight, blood pressure, insulin resistance, and norepinephrine (NE) kinetics using a two-compartment model. The HFD resulted in weight gain, hypertension, and insulin resistance. During the 6 weeks of the HFD, although plasma NE concentration trended toward increasing (P=.09), SNS, assessed by NE kinetic studies, significantly increased (P=.009). Within 1 week of starting the HFD, NE release into the extravascular compartment (NE(2)) increased from 3.44+/-0.59 microg/mL to 4.87+/-0.80 microg/mL (P<.01) and this increase was maintained over the next 5 weeks of the HFD (NE(2) at week 6 was 4.66+/-0.97 microg/mL). In addition to the increased NE(2) there was also a significant increase in NE clearance (P=.04). There were significant correlations between the increase in NE(2) and both the development of insulin resistance and hypertension. This study supports the hypothesis that activation of the SNS plays a pivotal role in the metabolic and hemodynamic changes that occur with weight gain induced by HFD.

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    ABSTRACT: High fructose consumption contributes to metabolic syndrome incidence while exercise training promotes several beneficial adaptations. In this study, we demonstrated the preventive role of exercise training in the metabolic syndrome derangements in a rat model. Wistar rats receiving fructose overload in drinking water (100g/l) were concomitantly trained on a treadmill (FT) or kept sedentary (F) for 10 weeks. Control rats treated with normal water were also submitted to exercise training (CT) or sedentarism (C). Metabolic evaluations consisted of the Lee index, glycemia and insulin tolerance test (kITT). Blood pressure (BP) was directly measured while heart rate (HR) and BP variabilities were evaluated in time and frequency domains. Renal sympathetic nerve activity was also recorded. F rats presented significant alterations when compared to all the other groups in insulin resistance (F:3.4±0.2; C:4.7±0.2; CT: 5.0±0.5 FT: 4.6±0.4 mg/dl/min), mean BP (F:117±2; C:100±2; CT:98±2; FT:105±2mmHg) and Lee index (F=0.31±0.001; C=0.29±0.001; CT=0.27±0.002; FT=0.28±0.002 g/mm), confirming the metabolic syndrome diagnosis. Exercise training blunted all these derangements. Additionally, FS group presented autonomic dysfunction in relation to the others, as seen by an approximate 50% decrease in baroreflex sensitivity and 24% in HR variability, and increases in sympathovagal balance (140%) and in renal sympathetic nerve activity (45%). These impairments were not observed in FT group, as well in C and CT. Correlation analysis showed that both Lee index and kITT were associated with vagal impairment caused by fructose. Therefore, exercise training plays a preventive role in both autonomic and hemodynamic alterations related to the excessive fructose consumption.
    Journal of Applied Physiology 01/2013; 114(6). DOI:10.1152/japplphysiol.00586.2012 · 3.43 Impact Factor


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