Effects of chronic mirabegron treatment on metabolic and cardiovascular parameters as well as on atherosclerotic lesions of WHHL rabbits with high-fructose high-fat diet-induced insulin resistance.

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Background and aimMetabolic syndrome (MetS) is a global health and economic burden. Finding a suitable pharmacological approach for managing this syndrome is crucial. We explored the therapeutic potential of mirabegron (MIR), a β3-adrenergic receptor agonist, as a repurposed agent for the treatment of MetS and its cardiovascular consequences. MethodsThirty Watanabe heritable hyperlipidemic rabbits (WHHL) were divided into 3 groups: control, high-fructose high-fat diet (HFFD) and HFFD + MIR that received a chow diet, HFFD and HFFD along with MIR treatment, respectively. The protocol lasted for 12 weeks, during which weight and abdominal circumference were monitored; plasma fasting levels of lipids, glucose and insulin were measured and an intravenous glucose tolerance test (IVGTT) was performed. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Cardiac function was assessed using in-vivo and ex-vivo approaches. Vascular reactivity was estimated via isolated carotid arteries method. Aortic atherosclerosis was evaluated using histological and immuno-histochemical techniques. ResultsIn contrast to the HFFD group, MIR-treated rabbits showed fasting insulin, HOMA-IR and TG levels stabilization and exhibited improved cardiac inotropy and lusitropy, while on the other hand, displayed aggravated atheroma plaque development. ConclusionLong-term treatment with MIR prevented the increase in TG levels and the establishment of IR and enhanced the cardiac function of a rabbit animal model of MetS with combined dyslipidemia and IR.