Mirabegron alleviates fructose induced nonalcoholic fatty liver disease in rats: Insights into the underlying mechanisms

Abstract

Aim

Non-alcoholic fatty liver disease (NAFLD) is one of the progressive and chronic disease encompass a range of conditions such as non-alcoholic steatohepatitis (NASH) and cirrhosis. The present study is aimed to elucidate the possible actions of mirabegron, a β3-adrenoreceptor agonist used in the treatment of over active bladder, against NAFLD induced by fructose.

Method

30 male Wistar rats were randomized into 5 groups (A) Veh, (B) Fru, (C) Fru + Sita, (D) Fru + Mira and (E) Fru + Mira + Resv. Rats of respective groups were treated with mirabegron (10 mg/kg, p.o.), sitagliptin (10 mg/kg, p.o.) and resveratrol (20 mg/kg, p.o.) daily for 14 days. Fructose water was given to all rats to induce NAFLD till end of the study. Simultaneously, biochemical analysis such as glucose, SGOT, SGPT, HDL, LDL, TC and TG were performed to assess the disease progression. In the end of study hepatic biochemistry, SOD, MDA, GSH, inflammatory markers such as TNF-α, IL-1β and Hematoxylin and Eosin (H&E) analysis were performed.

Key findings

The NAFLD rats exhibited a significant weight gain, substantial increase in liver enzymes, glucose, circulating and hepatic total cholesterol, triglycerides, inflammatory cytokines and histological analysis showed hepatic steatosis and inflammation in the Fru group. In contrast, mirabegron alone and in combination with antioxidant provided a promising data on ameliorative effect on hepatic inflammation and steatosis caused by fructose. As a result, mirabegron is found to be a promising therapeutic treatment strategy for NAFLD and its associated complications.

Significance

Collectively, findings in this present study revealed that mirabegron reversed NAFLD by suppressing fructose mediated inflammation, oxidative stress and steatosis.