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. 2010 Feb 1;12(2):117-24.
doi: 10.1111/j.1751-7176.2009.00230.x.

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

Albert P Rocchini  1 , John Q Yang, Marla J Smith, Mark A Supiano
Affiliations

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

Albert P Rocchini et al. J Clin Hypertens (Greenwich). .

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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Figures

Figure 1
Figure 1
(A) The regression relationship between the change in NE release into the extravascular compartment (ΔNE2) after 1 week of the high fat diet and the change in insulin mediated glucose uptake (Δ MPRF) in mg glucose per kg of pre‐fat body weight per min. The data from the seven animals that had week 1 measurements made are shown. (B) The regression relationship between the change in NE release into the extravascular compartment (ΔNE2) after 6 weeks of the high fat diet and the change in insulin mediated [2 mU/(kg min)] glucose uptake (Δ MPRF) in mg glucose per kg of pre‐fat body weight per min. The data from all eight animals that had week six measurements made are shown.
Figure 2
Figure 2
(A) The regression relationship between the change in NE release into the extravascular compartment (ΔNE2) after 1 week of the high fat diet and the change in mean arterial pressure (ΔBP). The data from the seven animals that had week 1 measurements made are shown. (B) The regression relationship between the change in NE release into the extravascular compartment (ΔNE2) after 6 weeks of the high fat diet and the change in mean arterial pressure (ΔBP). The data from all eight animals that had week six measurements made are shown.
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