Cotadutida (análogo a oxintomodulina) e tecido adiposo branco epididimário em camundongos obesos

Abstract

Obesity and inflammation of adipose tissue are associated with insulin resistance and type 2 diabetes mellitus (DM2). Cotadutida is a double agonist GLP-1/glucagon in preclinical study indicated to treat DM2 and has anti-obesity effect. Diet-induced obese C57BL/6 mice were treated for four weeks with coductide at a dosage of 30nmol/kg. The study aimed to investigate the effects of coductide in an obese mouse model, emphasizing epididymal white adipose tissue (EWAT), inflammation and endoplasmic reticulum (ER) stress. Cotadutide disrupted body mass and glucose intolerance/insulin resistance and increased insulin sensitivity in obese mice. In addition, codutide had beneficial effects on plasma markers leptin, adiponectin, monocyte chemoattractant protein 1, resistin, interleukin 6 and tumor necrosis factor alpha, and pro-inflammatory and ER stress markers in BAT. Cotadutide also had effects considered on the related aspects of the TABe, with reduction of markers related to hypertrophy, adipocyte perspective and apoptosis. In conclusion, in obese mice, coductide leads to weight loss and controls insulin resistance, with improvement in insulin sensitivity. Cotadutide absorbed inflammatory cytokines from adipose tissue, as well as ER stress, with reduced adipocyte hypertrophy and apoptosis. These effects are very satisfactory in the treatment of DM2 and associated obesity, which indicate positively for its use as a drug in preclinical analysis