Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease

Sedentary lifestyle and poor dietary choices are leading to a weight gain epidemic and increasing the risk for developing nonalcoholic fatty liver disease (NAFLD). NAFLD is a group of diseases with too much fat in liver in the absence of excess alcohol consumption. NAFLD encompasses a histological spectrum ranging from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. NAFLD is estimated to affect 25% of the worldwide population\[1\] and 15.35% of adults in shanghai urban area\[2\]. Epidemiological data showed that the fatty liver may predict, independent of other factors, the metabolic syndrome, type 2 diabetes, and cardiovascular disease. Therefore, we may prevent those diseases by treating NAFLD.Life style intervention including activity and reducing energy intake is recommended by health care providers for optimal health and is the most common prescribed therapy for individuals diagnosed with NAFLD. TZDs are oral glucose-lowering medications used to treat type 2 diabetes that enhance insulin sensitivity. The strong relationship between insulin resistance and NAFLD suggests that insulin sensitizing therapies such as TZDs might be beneficial in the prevention or improvement in NAFLD.TZDs bind to the peroxisome proliferator-activated receptors (PPARs), in part, by facilitating enhanced TG storage by adipocytes, suppressing the ectopic storage of lipids into liver and skeletal muscle. In addition, TZDs appear to have anti-inflammatory properties, inhibiting adipocyte gene expression and reducing circulating levels of TNFα\[3\] and resistin\[4\], and increasing adiponectin concentrations\[5\]. Some researches demonstrated that pioglitazone(a TZD) significantly reduced liver fat content of NAFLD, and ameliorated biological parameters and liver histology of NASH\[6\]. However, there have not been similar data of treating chinese NAFLD with pioglitazone. Berberine (BBR), a compound isolated from a Chinese herb was identified by Weijia \[7\] as a new cholesterol-lowering drug with a mechanism different from that of statin drugs. BBR elevates LDL receptor(LDLR) expression through a post-transcriptional mechanism that stabilizes the LDLR-mRNA. Considering the close relationship between NAFLD and lipid metabolism, we assume that BBR may be effective for NAFLD by improving lipid metabolism. In order to evaluate these hypotheses, we plan to treat a group of NAFLD patients with impaired glucose regulation (IGR) or T2DM with pioglitazone or BBR in a randomized, open, controlled trial for 16 weeks.