title: Serial changes in norepinephrine kinetics associated with feeding dogs a high-fat diet.
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.
authors.affiliation: Department of Pediatrics, Pediatric Cardiology Division, University of Michigan, Ann Arbor, MI 48109-5204, USA. rocchini@umich.edu
authors.forename: Albert P
authors.initials: AP
authors.lastname: Rocchini
authors.forename: John Q
authors.initials: JQ
authors.lastname: Yang
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Smith
authors.forename: Mark A
authors.initials: MA
authors.lastname: Supiano
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004041:Dietary Fats; D004285:Dogs; D005260:Female; D006801:Humans; D006973:Hypertension; D007333:Insulin Resistance; D008297:Male; D009638:Norepinephrine / Q000096:biosynthesis / Q000097:blood / Q000493:pharmacokinetics*; D012307:Risk Factors; D013223:Statistics as Topic; D013564:Sympathetic Nervous System; D015430:Weight Gain
chemical_list: D004041:Dietary Fats; D009638:Norepinephrine