The Takeda G-protein-coupled receptor 5 (TGR5) is a functional receptor which mediates a variety of metabolic and immune processes and is involved in the regulation of adipocyte pathophysiology. Experimental data from animal models show that TGR5 promotes mitochondrial function and increases ¿-oxidation and lipolysis in the adipose tissue, overall reducing lipid accumulation. Moreover, TGR5 activation is demonstrated to increase the energy expenditure and displays central anorexigenic effects in mice. Conversely, data on the expression of TGR5 in humans are very limited.
Therefore, this study proposal aims to explore the expression of TGR5 in human visceral adipose tissue (VAT) and to investigate correlates of differential VAT TGR5 expression in obese patients. This project will be carried out in a population of 50 obese individuals candidate to bariatric surgery for clinical purposes. Specific objectives will be: 1) to study the relationship between VAT TGR5 and presence of insulin resistance-associated disorders, i.e. abnormal glucose metabolism and impaired lipid profile; 2) to investigate the association between the TGR5 expression and the presence of signs of VAT dysfunction, as indicated by local inflammation and impaired lipid trafficking; 3) to test whether VAT TGR5 expression at baseline may predict metabolic outcomes of bariatric surgery at the 6-month post-intervention evaluation.
TGR5 represents a primary regulator of adipose tissue homeostasis and is a pharmacologically targetable receptor; therefore, this study will add insights on VAT pathophysiology in human obesity and might open a new scenario towards novel treatments for metabolic disorders.
