BACKGROUND:

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide. Pioglitazone is a pharmacologic agonist of peroxisome proliferators-activated receptor-γ (PPAR-γ) that was reported to ameliorate hepatic steatosis and inflammatory changes.

OBJECTIVE:

We aimed to evaluate the effects of pioglitazone in NAFLD and investigate the underlying mechanism by testing platelet derived growth factor (PDGF) and tissue inhibitory of metalloproteinase-2 (TIMP-2).

METHODS:

A total of C57BL/6 wild-type mice were randomized to three groups, control group (NC, n= 60), high-fat control group (HF, n= 60), and pioglitazone treatment group (L, n= 60). Mice were administrated with high-fat diet to construct NAFLD model. Enzyme-linked immunosorbent assay (ELISA) was used to measure protein expression of PDGF and TIMP-2. Liver histology samples were stained with hematoxylin and eosin (H&E).

RESULTS:

Upon pioglitazone treatment, the PDGF and TIMP-2 expression levels were decreased compared with high-fat diet-fed mice devoid of drug stimulation. Analysis of liver histology showed pioglitazone treatment could reduce steatosis and inflammatory changes, which was helpful to inhibit hepatic fibrosis in NAFLD mice.

CONCLUSIONS:

The study showed pioglitazone might exert an inhibitory effect on hepatic inflammation and fibrosis in NAFLD. Moreover, this study provided novel evidence for the promising clinical application of pioglitazone in intervening NAFLD.

1. Background

Nonalcoholic fatty liver disease (NAFLD) is an umbrella term for a spectrum of conditions characterized by lipid deposition in hepatocytes. With the improvement of living standard, NAFLD is increasingly common worldwide and patients trend to suffer this disease at a younger age. In the United States, it is estimated to occur in one-third of the general population [1, 2, 3]. From a pathological point of view NAFLD may be classified into nonalcoholic simple fatty liver (NAFL, or steatosis), nonalcoholic steatohepatitis (NASH-fatty changes with inflammation and hepatocellular injury or fibrosis), and advanced cirrhosis. Although simple steatosis will usually follow a slow course, it is well documented that it can progress to NASH and fibrosis [4], and approximately 15% to 25% of patients with NASH progress to cirrhosis and its complications over 10 to 20 years. Patients with the latter two diseases are at a significant risk of increasing morbidity [5, 6, 7]. Although the clinical course of NAFLD is variable, the most prevalent causes of deaths in NAFLD patients are cardiovascular disorders and malignancy followed by liver-related deaths [8]. The pathogenesis of NAFLD is multifactorial and epidemiological associations strongly support the notion that NAFLD is closely associated with MetS and its individual components [1, 9]. Currently, NAFLD appears as a global public medical hotspot, where multiple insulin resistance (IR)-related complications are involved [2, 8]. There is a directional association between NAFLD and metabolic syndrome (MS), MS plays an crucial role for the onset and perpetuation of NAFLD and, in return, NAFLD may be also a cause of MS [10, 11].