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Title: Impact of dietary manipulation on cardiac hypertrophy
Author: Butler, Thomas J.
Awarding Body: University of Hull
Current Institution: University of Hull
Date of Award: 2012
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Left ventricular hypertrophy (LVH) is a significant risk factor for the development of heart failure (HF), the incidence of which is increased by obesity. Diets high in fat and sugar have been linked with the development of the metabolic syndrome and obesity, and may expose the heart to a unique environment via the differential actions of dietary macronutrients. The main objectives of this study were to determine the effect of differing dietary regimens upon (i) the progression of LVH and whole organism morphology (ii) function and metabolism in the hypertrophied heart, and (iii) cardiac ceramide content. Cardiac hypertrophy was surgically induced in male Sprague-Dawley rats via abdominal aortic constriction (AC). Animals were assigned to either a diet containing 5% sucrose/7% fat (standard diet, SD), 9 % sucrose/45 % fat (high-fat diet, HFD), or 14% sucrose/44% fat (western diet, WD) for 9 weeks. LVH was observed in all AC groups but was greatest in those fed a SD or WD. Both HFD and WD resulted in a significant increase in abdominal fat mass, which was positively associated with serum concentrations of leptin. In vitro cardiac function was unaltered by any dietary regimen alone, but was significantly enhanced in hypertrophied hearts from HFD and WD-fed animals, consistent with a compensated phase of hypertrophic remodelling. This was accompanied by a small reduction in palmitate oxidation and increased reliance upon lactate, an effect which was exacerbated in hearts from WD-fed animals. In WD-fed animals, there was a substantial increase in cardiac triglyceride (TG), which was not affected by AC. PPARα protein was reduced following AC in the hearts of animals fed a SD or WD, whereas the HFD prevented this decline. CD36 protein expression was not different between control and AC animals, but was highest in those fed a WD. In addition to elevated TG, WD hearts also exhibited a significant accumulation of long-chain ceramide species (C16-C24) compared with other dietary groups; consistent with metabolic remodelling. This effect was observed independent of AC. In order to simulate a model of HF, WD animals were treated with adriamycin (ADR), and cardiac ceramide content was further increased with the specific accumulation of C16 and C18 ceramide. These findings suggest that dietary macronutrient composition can have a profound effect upon the progression of LVH. Furthermore, the enhanced ceramide content in WD hearts indicates that the macronutrient composition of this dietary profile is most deleterious to the hypertrophied heart. Prolonged exposure of the hypertrophied heart to the WD may lead to increased apoptosis and accelerate the transition to HF.
Supervisor: Seymour, Anne-Marie ; Ashford, David Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine