Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease (NAFLD) in rats

Abstract

Abstract:Objective: The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone (PGZ) acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding. Methods: The rats were separated randomly into 6 groups: model group I were fed high fat diet for 8 weeks, PGZ prevention group were given PGZ 4 mg/(kg⋅d) simultaneously, while control group I were fed normal food for 8 weeks; model group II were fed high fat diet for 16 weeks, PGZ treatment group were given PGZ 4 mg/(kg⋅d) orally simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group II were fed normal food for 16 weeks. The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), tumor necrosis factor alpha (TNF-α), fasting blood glucose (FBG), fasting plasma insulin (FINS), HOMA (homeostasis model assessment) insulin resistance index (HOMA-IR), and the liver histology of rats of all groups were assayed. Results: After 8 weeks, the liver in model group I showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT, AST, ALP, TNF-α were significantly increased (P<0.05) compared with control group I. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased (P<0.05) compared with model group I. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group II rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels of ALT, AST, ALP, FINS and HOMA-IR were significantly increased (P<0.05) in model group II compared with control group II. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT, ALP, TNF-α and HOMA-IR were significantly decreased compared with model group II. Conclusion: Insulin resistance plays a role in the pathogenesis of NAFLD in rats. Pioglitazone can attenuate insulin resistance and biochemical and histological injury in high fat-induced fatty liver in rats.

Inhibition of hepatic interleukin-18 production by rosiglitazone in a rat model of nonalcoholic fatty liver disease

“…In line with the above reports [12,21,22] , our study showed that increased liver weight and liver weight index, elevated serum liver enzyme levels and altered liver histological conditions including steatosis, inflammation and fibrosis were observed in the NAFLD rats, which were significantly improved 4 wk after RGZ treatment. In agreement with previous reports [12,21] , the present study also showed that the levels of serum insulin, leptin, FFA and triglycerides as well as HOMA-IR were significantly increased, whereas the levels of serum adiponectin remarkably decreased in the NAFLD group. Four weeks after RGZ treatment, these abnormalities were significantly improved, suggesting that insulin resistance may play an important role in the pathogenesis of NAFLD.…”

“…These findings sug gest that insulin resistance contributes to the development of NAFLD and that insulin sensitizers may represent important agents for the treatment of NAFLD. Furthermore, the beneficial effects of insulin-sensitizing agents, RGZ [21,22] , pioglitazone [12] and [21] , on hepatic steatosis and inflammation have been confirmed in various animal models of NAFLD. Compared to metformin, RGZ appears to be a better drug for improving hepatic steatosis [21] .…”

“…Rats in the control group were maintained on the standard chow diet for 12 wk. A rat model of NAFLD was induced by a high-fat diet (standard chow diet + 10% lard + 2% cholesterol) for 8 wk as previously described [12] . Subsequently, rats in the RGZ-treated NAFLD group were treated with RGZ maleate (Avandia®, 4 mg/kg per day) via gavage, whereas rats in the NAFLD group were given normal saline for another 4 wk.…”

Thiazolidinedione induces a therapeutic effect on hepatosteatosis by regulating stearoyl‑CoA desaturase‑1, lipase activity, leptin and resistin

“…This result is supported by Xu et al (5) who used TZD at 4 mg for 8 weeks in HFCD rats. TZD may mitigate insulin resistance as well as histological injury and biochemical markers in high fat-induced fatty livers in rats as reported by Mohan et al (46) and Peng et al (23).…”

“…Hepatosteatosis is associated with metabolic syndrome, high alcohol consumption, a poor diet and obesity (1,5,6). The symptoms of hepatosteatosis are often nonspecific, which makes them easy to miss and means that hepatosteatosis can be difficult to diagnose (7).…”