Renal Cannabinoid Receptor Expression\ud and Function: Their Role in Obesity and\ud Diabetes

Obesity and diabetes are clearly established independent risk factors for renal\ud disease. Therapeutic targets have been investigated for their role in treating obesity\ud and diabetic associated renal damage. The endocannabinoid system is an important\ud endogenous lipid signalling system known to mediate glucose and lipid metabolism,\ud inflammation and energy storage. Specifically, diabetes mellitus and obesity induces\ud alterations in the expression of cannabinoid receptor 1 (CB1), cannabinoid receptor\ud 2 (CB2) and putative cannabinoid receptor G-protein coupled receptor 55 (GPR55)\ud in a tissue specific manner. Renal expression and function of these receptors,\ud particularly within the pathophysiological context of obesity and diabetes related\ud renal damage is poorly understood. The research presented in this thesis examines\ud the renal expression and function of CB1, CB2 and GPR55. The significant aim of\ud this PhD candidature was to examine the expression of cannabinoid receptors in the\ud kidney in obese and diabetic conditions. Subsequent studies sought to evaluate the\ud actions of selective manipulation of the receptors by synthetic compounds on\ud markers of renal damage and structure in an animal model of diet induced obesity\ud (DIO)