Abstract

Although the association between obesity and hypertension is well-known, the underlying mechanism remains elusive. Previously, we have shown that 3 week fat feeding in rabbits produces greater visceral adiposity, hypertension, tachycardia and elevated renal sympathetic nerve activity (RSNA) compared to rabbits on a normal diet. Because hyperinsulinaemia, hyperleptinemia, and dyslipidaemia are independent cardiovascular risk factors associated with hypertension we compared plasma insulin, leptin, and lipid profiles in male New Zealand White rabbits fed a normal fat diet (NFD 4.3% fat, n = 11) or high fat diet (HFD 13.4% fat, n = 13) at days 1, 2, 3 and weeks 1, 2, 3 of the diet. Plasma concentrations of diacylglyceride (DG), triacylglyceride (TG), ceramide and cholesteryl esters (CE) were obtained after analysis by liquid chromatography mass spectrometry. Plasma insulin and glucose increased within the first 3 days of the diet in HFD rabbits (P < 0.05) and remained elevated at week 1 (P < 0.05). Blood pressure and heart rate (HR) followed a similar pattern. By contrast, in both groups, plasma leptin levels remained unchanged during the first few days (P > 0.05), increasing by week 3 in fat fed animals alone (P < 0.05). Concentrations of total DG, TG, CE, and Ceramide at week 3 did not differ between groups (P > 0.05). Our data show plasma insulin increases rapidly following consumption of a HFD and suggests that it may play a role in the rapid rise of blood pressure. Dyslipidaemia does not appear to contribute to the hypertension in this animal model.

Highlights

  • Obesity is associated with increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA)

  • Circulating leptin concentrations were unaltered by a high fat diet (HFD) at day 3 but were markedly increased by week 3 whilst in the same time period, no evidence of dyslipidaemia was found

  • These data suggest hyperinsulinemia rapidly develops after the commencement of a HFD and is a likely mechanism by which haemodynamics and sympathetic tone may change rapidly in the fat-fed rabbit model of obesity related hypertension

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Summary

Introduction

Obesity is associated with increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). Accumulating evidence suggests these changes are due to greater circulating concentrations of the adipokine leptin (Burke et al, 2013; Lim et al, 2013) which strongly correlate with RSNA and MAP in animal models of obesity (Prior et al, 2010; Burke et al, 2013). We have previously shown that insulin signaling is one of the factors responsible for the development of obesity related hypertension which is later maintained by slowly rising circulating leptin concentrations (Lim et al, 2013)

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