THE ROLE OF SIRTUIN1 DURING HIGH-FAT FEEDING

Author: Kamelya Aliakbari

Aliakbari, Kamelya, 2014 THE ROLE OF SIRTUIN1 DURING HIGH-FAT FEEDING, Flinders University, School of Medicine

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Abstract

Background: More than half of the Australian adult population is overweight or obese. High-fat feeding is the main culprit for these staggering statistics. Oxidative stress, inflammation and decreased nitric oxide bioavailability in obese patients increase their likelihood of developing stroke or dementia. Purpose: Sirtuin 1 (SIRT1) is a protein deacetylase with known antioxidant properties and ability to enhance nitric oxide bioavailability. Studies from our laboratory and others have shown that high-fat feeding leads to SIRT1 depletion within the vasculature. In the present study, we tested the hypothesis that SIRT1 overexpression during high-fat feeding would attenuate the phenotypes of vascular ageing, including inflammation and oxidative stress. Methods: Wildtype (WT) and SIRT1 overexpressing mice (SIRT1-KI) were fed either a normal diet or high-fat diet for two months. At the end of the study, whole blood, plasma and vascular samples were obtained and stored for analysis. Results: WT mice on a high-fat diet displayed decreased SIRT1 protein expression and increased nitrotyrosine expression, as measured in the carotid artery, which were both prevented in SIRT1-KI mice. Conclusions: Our results highlight the potential benefits of targeting SIRT1 as a therapeutic strategy in reducing the clinical complications associated with vascular impairment during high-fat feeding.

Keywords: High-fat feeding,Oxidative stress,Nitric oxide,Sirtuin1 overexpression
Subject: Medicine thesis, Medical Biotechnology thesis, Biotechnology thesis

Thesis type: Masters
Completed: 2014
School: School of Medicine
Supervisor: Dr Elke Sokoya