Role of angiotensin in obesity: inflammation and autophagy

Abstract

Obesity is a chronic metabolic disease that may be associated with physiological disorders, such as diabetes mellitus (DM) and hypertension. Studies have shown common pathways linking obesity to insulin resistance and the renin-angiotensin system (RAS). Angiotensinogen (Agt) is the main precursor of RAS. Activation of Agt is often linked to dysfunctions in cellular processes, such as autophagy. In obesity, the pro-inflammatory profile in adipose tissue leads to the production of adipokines and cytokines that promote glucose intolerance and insulin resistance. Leukotriene B4 (LTB4) plays a central role in the establishment of insulin resistance and development of low grade inflammation in animal models. In adipose tissue of HFD induced T2D mice, monocyte recruitment, macrophage polarization into the M1 profile, proinflammatory cytokine production and insulin resistance have been shown to be dependent on LTB4 production. In liver and muscle LTB4 promotes inflammation and insulin resistance. We intend to investigate the involvement of leukotrienes in RAS in mice with obesity, with specific emphasis on the role of inflammation, autophagy and signaling of the insulin receptor in metabolically active organs/tissues. Understanding the molecular mechanisms involved in these diseases can bring a direct benefit to the patient, improving their quality of life, as well as reducing the public expenses resulting from the complications of these metabolic syndromes. (AU)