Investigating molecular adaptations in adipose tissue and skeletal muscle in response to intermittent fasting and exercise training

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Wilson, Robin A (2018) Investigating molecular adaptations in adipose tissue and skeletal muscle in response to intermittent fasting and exercise training. PhD thesis, Victoria University.

Abstract

The rapid rise in obesity prevalence appears to be a reflection of the changes in dietary and behavioural patterns, with eating habits shifting to higher consumption of energy-dense foods which are rich in fats and sugars, while at the same time, levels of physical activity are decreasing. These differences in energy intake and expenditure, often referred to as energy balance, have direct implications for weight regulation, with even small deviations in daily energy balance resulting in large body weight changes over the long term. Diet and exercise interventions aiming to shift the energy balance towards negative by either decreasing caloric intake and/or increasing physical activity have shown to be effective for weight loss. Many iterations of such dietary and physical activity interventions have been proposed, but intermittent fasting (IF) and high intensity interval training (HIIT) have recently been purported as effective strategies. Despite their effectiveness, the molecular mechanisms by which these lifestyle interventions induce their effects are unclear. Therefore, the purpose of this thesis was to examine the effects of IF and HIIT, alone and in combination, on anthropometric and metabolic health parameters in a model of diet-induced obese mice. To elucidate possible mechanisms of action, we investigated the impact of both lifestyle interventions on mRNA-miRNA regulatory networks, but more importantly, how such changes may translate into exercise- induced and diet-induced improvements in body composition and metabolic health. The findings from the thesis demonstrate that intermittent fasting with or without high intensity interval training resulted in significantly less weight gain in male mice despite concurrently consuming a high fat and sugar diet. The reduced weight gain was predominantly in the form of lower fat mass accumulation, with no significant loss in lean mass. These observations were supported by enhanced expression of adipose tissue genes relating to fragmentation of unilocular lipid droplets, lipolysis, fatty acid oxidation and efflux. Moreover, lower expression levels of leptin, pro-inflammatory markers and markers of hypoxia were also observed. These changes were also reflected by changes in miRNA-24, -222, -145 and -143. Within the skeletal muscle, the combination of diet and exercise demonstrated minimal impact on mRNA and miRNA expression markers relating to energy metabolism, however IF alone displayed significantly lower expression of all markers compared to control mice or other intervention groups. Interestingly, the changes in body composition, glycaemic control, lipid panels and expression of mRNA and miRNA seem to be gender specific with different responses, independent of intervention, demonstrated in male mice compared to the female mice. In conclusion, the novel results from this thesis have demonstrated superior effects on body composition and lipid profiles following combined IF and HIIT compared to either diet or exercise intervention alone while concurrently consuming a high fat and sugar diet. These observations are likely due to the physiological and biochemical changes that occur within the adipose and skeletal muscle tissue when creating a negative energy balance shift. The gender specific responses to the same diet and/or exercise intervention could indicate potential hormonal differences influencing metabolic control/adaptation in mice. Identification of important regulatory miRNAs through this thesis could provide potential therapeutic targets for obesity treatment and management.

Item type Thesis (PhD thesis)
URI https://vuir.vu.edu.au/id/eprint/42888
Subjects Current > FOR (2020) Classification > 3205 Medical biochemistry and metabolomics
Current > FOR (2020) Classification > 4207 Sports science and exercise
Current > Division/Research > College of Health and Biomedicine
Keywords molecular adaptations; adipose tissue; skeletal muscle; intermittent fasting; exercise; high intensity interval training; metabolic health; mice; obesity; miRNA
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