Efeito do tratamento crônico com liraglutida no desenvolvimento da aterosclerose em camundongas Knockout para o receptor de LDL (LDLr-/-)

Abstract

Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue widely used in the treatment of type 2 diabetes mellitus and as an adjunct in obesity management due to its multiple actions, such as appetite reduction and improved insulin secretion and action. Cardioprotective effects, including atherosclerosis prevention, have already been demonstrated. However, the literature still lacks studies evaluating the impact of liraglutide in females, particularly postmenopausal ones, to determine whether they could benefit from treatment when predisposed to atherosclerosis. Therefore, this study aimed to evaluate liraglutide treatment in LDL receptor knockout (LDLr-/-) mice, with or without estrogen deprivation. LDLr-/- and wild-type (C57) mice were divided into five experimental groups: Wild Type (WT), Sham with saline (S), Sham with liraglutide (SL), Ovariectomized with saline (O), and Ovariectomized with liraglutide (OL). LDLr-/- groups received a high-fat diet. The treatment consisted of subcutaneous administration of liraglutide at a dose of 1.2 mg/kg/day, divided into two daily doses of 0.6 mg/kg/day, for eight weeks. The results showed that liraglutide significantly reduced vascular lipid deposition, decreased caloric intake, prevented weight gain, and improved glucose tolerance. These findings suggest the therapeutic potential of liraglutide in mitigating the deleterious effects associated with estrogen deprivation and predisposition to atherosclerosis development.