The acute effects of exercise and postprandial hypertriglyceridemia on physiological and biochemical risk factors for disease

Abstract

Oxidative stress is an integral component in the pathology of cardiovascular disease, the leading cause of global mortality. Metabolic disturbances observed during postprandial hypertriglyceridemia have been identified as an independent risk factor within the aetiology of this disease, mainly via oxidative stress and pro-inflammatory mechanisms. Physical exercise has shown promising signs in ameliorating the symptoms of cardiovascular disease, but its role in the generation of oxidative stress, inflammation and associated molecular damage to lipids, protein and DNA is not fully understood. The principal aim of this thesis is to examine the transient effects of differing walking exercise trials on free radical metabolism, inflammation and subsequent molecular damage over time, in conditions of fasting and metabolic disturbance.

In study 1, seventeen healthy male participants (22.6 ± 4.6 years; 179.2 ± 5.6 cm; 79 ± 10.6 kg) undertook a randomised crossover exercise trial. The findings demonstrate that exercise, regardless of intensity (continuous at 60% VO2max or intermittent at 80% VO2max) promotes an increase in systemic cytokine concentrations. IL-6 increased immediately post-exercise (3-fold and 7-fold relative increase for the continuous and intermittent bouts respectively) and remained elevated at 4 h. Likewise, TNF-α followed a similar trend with relative increases of 1.5-fold and 2-fold for the respective continuous and intermittent bouts. This response occurs independently of oxidative stress (a current theory proposed to explain this occurrence), highlighting alternative mechanisms may be in operation. While lipid peroxidation and free radical production did not change, α-tocopherol increased with both trials and lycopene decreased at 2 hours post vigorous intermittent exercise compared to the moderate intensity condition. This suggests a heightened antioxidant response and preventive measure to avoid oxidative damage.

Twelve healthy male participants (22.4 ± 4.1 years; 179.2 ± 6 cm; 84.2 ± 14.7 kg) completed studies 2 and 3, which differed by way of the exercise and meal timing. The findings illustrate that 1 hour of moderate intensity walking exercise (60% maximal heart rate) whether performed prior to or following consumption of a high fat meal, has no effect on DNA instability as this increased during both trials. Pooled data from study 2 suggests DNA tail intensity increased post-meal with peak damage occurring at 4 h compared to baseline (20% rise). Similarly, pooled data indicates DNA damage increased post-meal in study 3 andremained elevated thereafter, peaking at the pre-exercise / pre-rest time point (45% rise) compared to baseline. This change in both was associated with an increase in lipid peroxidation, free radical production, triglycerides and inflammation (measured via erythrocyte sedimentation rate) highlighting potential mechanisms of action. Alongside this rise in oxidative stress, non-enzymatic antioxidant mobilisation also increased (γ-tocopherol and α-tocopherol) indicating a possible operational pathway that may attenuate the extent of damage.

The results of the studies showed that walking exercise promoted changes in cytokine secretion and antioxidant status but proved ineffective in alleviating postprandial hypertriglyceridemia-induced oxidative stress and subsequent molecular damage to lipids and DNA. It is worth considering alternative exercise intensities and durations as they may assist in attenuating oxidative stress and as a result may contribute to reductions in molecular damage. Additionally, further research is required to identify the precise biochemical mechanisms responsible for this type of response.

Date of Award	Oct 2016
Original language	English
Supervisor	Marie Murphy (Supervisor), Gareth Davison (Supervisor) & Conor McClean (Supervisor)