Combination of vildagliptin and rosiglitazone ameliorates nonalcoholic fatty liver disease in C57BL/6 mice

Abstract

Objectives:To evaluate the effect of vildagliptin alone and in combination with metformin or rosiglitazone on murine hepatic steatosis in diet-induced nonalcoholic fatty liver disease (NAFLD).Materials and Methods:Male C57BL/6 mice were fed with high fat diet (60 Kcal %) and fructose (40%) in drinking water for 60 days to induce NAFLD. After the induction period, animals were divided into different groups and treated with vildagliptin (10 mg/kg), metformin (350 mg/kg), rosiglitazone (10 mg/kg), vildagliptin (10 mg/kg) + metformin (350 mg/kg), or vildagliptin (10 mg/kg) + rosiglitazone (10 mg/kg) orally for 28 days. Following parameters were measured: body weight, food intake, plasma glucose, triglyceride (TG), total cholesterol, liver function tests, and liver TG. Liver histopathology was also examined.Results:Oral administration of vildagliptin and rosiglitazone in combination showed a significant reduction in fasting plasma glucose, hepatic steatosis, and liver TGs. While other treatments showed less or no improvement in the measured parameters.Conclusions:These preliminary results demonstrate that administration of vildagliptin in combination with rosiglitazone could be a promising therapeutic strategy for the treatment of NAFLD.

Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models

“…If NASH persists, an inflammatory necrosis cycle occurs, which then progresses to fatty liver fibrosis and fatty liver cirrhosis. In Western countries, NAFLD has become a common chronic liver disease with approximately 20% of the population suffering from this disease, and the rate of NAFLD in the obese population is 70%–80% [ 7 , 8 , 9 ]. In approximately 25% of patients with NASH, fibrosis of the hepatic portal vein [ 10 ] evolves into liver cirrhosis.…”

Comparison of efficacy of anti-diabetics on non-diabetic NAFLD: A network meta-analysis

“…Both pioglitazone and rosiglitazone belong to TZD functioning as highly selective PPAR-γ agonists, which is a key factor in the regulation of glucose and lipid metabolism ( Francque et al, 2021 ). Activation of PPAR-γ increases adipocyte uptake of free fatty acids, protecting the liver, skeletal muscle, and beta cells against the deleterious metabolic effects of lipid poisoning ( Mookkan et al, 2014 ). PPAR-γ receptors are widely distributed in adipose tissue and hepatic Kupffer cells, which are associated with liver fibrosis ( Raschi et al, 2018 ; American Diabetes Association, 2019 ; Francque et al, 2021 ).…”

“…Interestingly, Mookkan discovered that hepatic steatosis and TGs were significantly reduced in the mice treated with vildagliptin and rosiglitazone combo ( Mookkan et al, 2014 ). However, clinical investigations are necessary to establish this finding.…”

Altered pharmacokinetics of rosiglitazone in a mouse model of non-alcoholic fatty liver disease

“…In the present study, we utilized a validated model of NAFLD in C57BL/6 mice [14]. The current model displayed most of the characteristic features of NAFLD like obesity, metabolic syndrome and pro-inflammatory condition along with accumulation of fat in the liver.…”

“…Hence, the aim of the present study was to investigate the effect of the NAFLD condition on the pharmacokinetics of RSG in a mice model after a single oral administration. For this, we utilized an established an animal model of NAFLD in mice [14].…”