The Role of Atypical Cannabinoid Ligands O-1602 and O-1918 on Skeletal Muscle Homeostasis with a Focus on Obesity.

O-1602 and O-1918 are atypical cannabinoid ligands for GPR55 and GPR18, which may be novel pharmaceuticals for the treatment of obesity by targeting energy homeostasis regulation in skeletal muscle. This study aimed to determine the effect of O-1602 or O-1918 on markers of oxidative capacity and fatty acid metabolism in the skeletal muscle. Diet-induced obese (DIO) male Sprague Dawley rats were administered a daily intraperitoneal injection of O-1602, O-1918 or vehicle for 6 weeks.

Direct activation of the proposed anti-diabetic receptor, GPR119 in cardiomyoblasts decreases markers of muscle metabolic activity.

GPR119 agonists are emerging rapidly as a pharmaceutical treatment of diabetes. Diabetes is a known risk factor for cardiovascular disease yet the cardiac-specific consequences of GPR119 activation are unknown. This study demonstrated that GPR119 agonism in cardiac myoblasts reduces metabolic activity in high and low concentrations of fatty acids, with high concentrations of palmitate largely attenuating the effects of the GPR119 agonist, PSN632408.

GPR120 agonism as a countermeasure against metabolic diseases.

Obesity, type 2 diabetes mellitus and cardiovascular disease are at epidemic proportions in developed nations globally, representing major causes of ill-health and premature death. The search for drug targets to counter the growing prevalence of metabolic diseases has uncovered G-protein-coupled receptor 120 (GPR120). GPR120 agonism has been shown to improve inflammation and metabolic health on a systemic level via regulation of adiposity, gastrointestinal peptide secretion, taste preference and glucose homeostasis.

The therapeutic potential of GPR43: a novel role in modulating metabolic health.

GPR43 is a receptor for short-chain fatty acids. Preliminary data suggest a putative role for GPR43 in regulating systemic health via processes including inflammation, carcinogenesis, gastrointestinal function, and adipogenesis. GPR43 is involved in secretion of gastrointestinal peptides, which regulate appetite and gastrointestinal motility.

Is GPR119 agonism an appropriate treatment modality for the safe amelioration of metabolic diseases?

Introduction: GPR119 is a recently deorphanised G-protein coupled receptor which has been suggested to be important in mediating systemic metabolic homeostasis. Research to date has primarily focused on the ability of GPR119 to promote euglycaemia and thus as a therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). Indeed, previous studies have shown that GPR119 promotes glucose-stimulated insulin secretion, pancreatic β-cell function and glucagon-like peptide-1 release, all of which provide valid mechanisms through which GPR119 may improve systemic glucose homeostasis.

Diet-induced obesity up-regulates the abundance of GPR43 and GPR120 in a tissue specific manner.

Background/aims: GPR43 and GPR120 have recently been deorphanised as receptors for fatty acids. Fatty acids mediate a variety of metabolic processes in the body, however, the effect these receptors have on metabolism is not fully understood. Here, we characterise the effect of diet-induced obesity on the expression of GPR43 and GPR120 in tissues important in maintaining metabolic health.

The role of angiotensin in obesity and metabolic disease.

Obesity is associated with increased body fat composition and elevated risk of metabolic and cardiovascular disease. The activity of the renin-angiotensin system is generally increased in obesity and experimental evidence has shown that angiotensin influences appetite and metabolism as well as mechanisms that induce adipose tissue growth and metabolism in peripheral organs. This review summarises some of the key evidence from animal and human experiments that links the renin-angiotensin system to obesity and metabolic disease.