Ursodeoxycholic Acid Ameliorates Fructose-Induced Metabolic Syndrome in Rats

Abstract

The metabolic syndrome (MS) is characterized by insulin resistance, dyslipidemia and hypertension. It is associated with increased risk of cardiovascular diseases and type-2 diabetes. Consumption of fructose is linked to increased prevalence of MS. Ursodeoxycholic acid (UDCA) is a steroid bile acid with antioxidant, anti-inflammatory activities and has been shown to improve insulin resistance. The current study aims to investigate the effect of UDCA (150 mg/kg) on MS induced in rats by fructose administration (10%) in drinking water for 12 weeks. The effects of UDCA were compared to fenofibrate (100 mg/kg), an agonist of PPAR-α receptors. Treatment with UDCA or fenofibrate started from the 6th week after fructose administration once daily. Fructose administration resulted in significant increase in body weight, elevations of blood glucose, serum insulin, cholesterol, triglycerides, advanced glycation end products (AGEs), uric acid levels, insulin resistance index and blood pressure compared to control rats. Moreover, fructose increased oxidative stress in aortic tissues indicated by significant increases of malondialdehyde (MDA), expression of iNOS and reduction of reduced glutathione (GSH) content. These disturbances were associated with decreased eNOS expression, increased infiltration of leukocytes and loss of aortic vascular elasticity. Treatment with UDCA successfully ameliorated the deleterious effects of fructose. The protective effect of UDCA could be attributed to its ability to decrease uric acid level, improve insulin resistance and diminish oxidative stress in vascular tissues. These results might support possible clinical application of UDCA in MS patients especially those present with liver diseases, taking into account its tolerability and safety. However, further investigations on human subjects are needed before the clinical application of UDCA for this indication.

Consequences of bile salt biotransformations by intestinal bacteria

“…101,102 Rodent models even suggest UDCA may be therapeutic in fructose-induced metabolic syndrome. 103 Recently, trials have been underway to determine the efficacy of UDCA to prevent colorectal adenoma recurrence, and results have been mixed. [104][105][106] Animal models have suggested that UDCA can prevent azomethane-induced colon carcinogenesis.…”

Role of PPARα in down-regulating AGE-induced TGF-β and MMP-9 expressions in chondrocytes

“…AGE generation is an unavoidable and irreversible process (Fu et al, 2014). Research has demonstrated that the generation and accumulation of a large number of AGEs in vivo play a vital role in the development and acceleration of OA (Mahmoud and Elshazly, 2014); moreover, these act as the molecular foundation for the effect of age on OA. However, its mechanism remains unclear.…”

Protective effect of ursodeoxycholic acid, resveratrol, andN-acetylcysteine on nonalcoholic fatty liver disease in rats

“…Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is used in this experiment as a reference treatment for NAFLD, and is known to act by competitive displacement of hepatotoxic hydrophobic endogenous bile acids that facilitate apoptosis, minimizing their toxicity and leading to a decrease in oxidative stress and hepatic injury (Mahmoud & Elshazly, 2014).…”