Roy, Anna (2017) The Effects O-1602, O-1918 or Different Dietary Fatty Acids have on Whole body and Skeletal Muscle Energy Homeostasis: A Focus on Putative Cannabinoid Receptors, Adiponectin and Fatty Acid Signalling. PhD thesis, Victoria University.

Abstract

The prevalence and incidence of obesity and related co-morbidities such as insulin resistance and type two diabetes mellitus (T2DM) are rapidly increasing world-wide. These health burdens negatively impact individuals, families, the community and the government, for a multitude of reasons. The search for suitable therapeutic targets for obesity, in combination with a healthy diet and increased physical activity is a strategy for weight management and associated co-morbidities such as T2DM. The endocannabinoid system is a lipid derived signalling system that is modulated by different dietary fatty acids and has a role in regulating energy homeostasis. Modulation of cannabinoid receptor 1 (CB1) reduces whole body adiposity and increases oxidative capacity within the skeletal muscle. The skeletal muscle is a major contributor to whole body energy metabolism through the oxidation of fatty acids, insulin signalling and glucose uptake, therefore understanding the impact that endocannabinoid pharmaceutics have on this tissue is essential. Putative endocannabinoid receptors including G Protein- Coupled Receptor (GPR55) and G Protein-Coupled Receptor 18 (GPR18) may potentially be beneficial pharmaceutical targets for obesity and associated co-morbidities. GPR55 expression is upregulated in visceral adipose tissue in obesity and T2DM. Surprisingly GPR55 knockout mice have increased adiposity and reduced physical activity. While GPR18 has been shown to be expressed in adipose tissue, its role in obesity is unknown. Furthermore the role that atypical cannabinoid compounds, O-1602 or O-1918 (which have/ are hypothesised to have affinities for these receptors and therefore modulate these putative cannabinoid receptors) have in obesity and skeletal muscle homeostasis, following chronic treatment has yet to be determined. The dietary intake of specific fatty acids can also alter circulating endocannabinoid concentrations depending on the type of fatty acid consumed. The effect that different dietary fatty acids have on the putative cannabinoid receptors GPR55 and GPR18 and whole body energy homeostasis in obesity is unknown. Therefore the overall focus for this thesis was to determine the role that atypical cannabinoids have on homeostatic skeletal muscle signalling and whole body energy metabolism in obesity. In addition to this, the effect that different dietary fatty acids have in obesity and whole body energy metabolism were also determined, which may partially be attributed to GPR55 and GPR18 signalling.

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