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EXPLORING LINKS BETWEEN OXIDATIVE STRESS, METABOLIC DYSREGULATION AND THE ONSET OF CARDIO-METABOLIC DISEASES

EXPLORING LINKS BETWEEN OXIDATIVE STRESS, METABOLIC DYSREGULATION AND THE ONSET OF CARDIO-METABOLIC DISEASES

Faadiel ESSOP

(Stellenbosch, South Africa)

EXPLORING LINKS BETWEEN OXIDATIVE STRESS, METABOLIC DYSREGULATION AND THE ONSET OF CARDIO-METABOLIC DISEASES

11:30 AM 23 April / Nisan 2018

Abstract

Although frequent sugar-sweetened beverage (SSB) consumption correlates with the development of obesity, diabetes and heart diseases, the underlying molecular mechanisms remain elusive. Moreover, previous laboratory-based studies have employed relatively large SSB dosages that may not reflect real-life consumption patterns, thus potentially skewing the significance of findings generated. For this study, we therefore hypothesized that frequent ‘’moderate’’ SSB consumption triggers oxidative stress and metabolic dysregulation in rats that result in impaired cardiac function.

A model of long-term SSB consumption was established where male Wistar rats (~200 gr) were gavaged with 3-5.1 mL of a local SSB daily for 6 months (~125 mL/day in human terms). In parallel, a control group was gavaged with an iso-volumetric amount of water. Isolated rat liver and heart tissues were subsequently analyzed for oxidative stress markers. As previous research work conducted in our laboratory implicated dysregulation of non-oxidative glucose pathways in the development of cardio-metabolic complications, markers of the polyol pathway, hexosamine biosynthetic pathway (HBP), advanced glycation end-products, and PKC were also assessed. A proteomics analysis was completed for the liver samples, while ex vivo and in vivo heart functional assessments were also performed.

Our data demonstrate that SSB consumption elicited moderate weight gain, while fasting metabolite levels generally remained unchanged vs. controls. Heart function was not significantly altered after 6 months of SSB intake, while myocardial cholesterol and triglyceride levels were not changed. There were early signs of oxidative stress in both liver and heart tissues, but counteracted by compensatory mechanisms. However, SSB intake triggered the activation of the HBP and the PKC pathways in heart and liver tissues, respectively vs. controls. The liver proteomic analysis revealed that the expression level of 140 proteins was significantly altered in the SSB group, with a major finding that SSB consumption induces hepatic endoplasmic reticulum stress. These findings reveal early SSB-induced metabolic changes in liver and heart tissues that may place organisms at risk in the long-term despite an apparently ‘’healthy’’ phenotype.

Keywords: Sugar-sweetened beverages; cardio-metabolic perturbations; oxidative stress