Studies on transient receptor potential TRP channel based dietary triagonists for obesity prevention

Abstract

In the present thesis we aimed to develop a polypharmacological approach using bioactive natural compounds to prevent obesity. We combined the sub-effective doses of three natural TRP channel agonists (capsaicin, menthol and cinnamaldehyde) and evaluated their anti-obesity potential using in-vitro and in-vivo models. The in-vitro experiments show that the tri-agonist combination formed using one-fifth doses of individual agonists enhanced energy expenditure phenotype in the cells. Tri-agonist combination enhanced glucose utilization, delayed cell cycle progression, enhanced mitochondrial biogenesis and browning of adipocytes. The preventive and therapeutic in-vivo experiments show that the combination has potential anti-obesity effects as it improved glucose homeostasis, enhanced insulin sensitivity, prevented WAT hypertrophy, enhanced mitochondrial activity and browning in HFD-fed mice. Overall, the work presented in this thesis provide evidence for the benefits of dietary TRP channel activating tri-agonist on adipogenesis, glucose homeostasis, insulin sensitivity, energy expenditure and obesity (preventive and therapeutic effects). Novel combination based pharmacological approaches (dual and triple incretins) are the probable forthcoming advances to clinical practice for preventing obesity and its metabolic consequences. In future, attempts should be made to formulate functional foods or nutraceuticals, combining these agents which can induce energy expanding phenotype and improved metabolic profile. Formulated functional foods and nutraceuticals should be clinically validated for their effects on energy expenditure both in healthy individuals and obese participants. newline