We also acknowledge the major contribution http://www.selleckchem.com/products/GDC-0449.html made by Sandrine Kraemer to this trial.
Nonalcoholic fatty liver disease (NAFLD), the most common hepatic disorder of industrialized countries, affects approximately 15�C25% of the general population (1). Previously unrecognized until the early 1980s, NAFLD is a progressive disease with an etiology related to recent changes in diet and lifestyle. In a number of cases, patients go on to develop nonalcoholic steatohepatitis (NASH), a more severe disease associated with obesity, insulin resistance (2), and mitochondrial dysfunction (3). Estimations of the incidence of NASH in the general population vary from 2�C3% (4), with indications that this condition is becoming increasingly prevalent even in the pediatric population (5), who are nearly always insulin resistant regardless of body mass index (6).

Insulin resistance is a common occurrence in obesity, metabolic syndrome, and type 2 diabetes and can be induced experimentally by high-fat diets (7). Since 1970, consumption of oils and fats in the US has increased by 62% (8), with vegetable oil assuming a larger percentage of total fat intake. Trans-fatty acids (TFAs) derived from vegetable oils and shortenings now accounting for between 1.7% and 8% of the world dietary fat consumption (9). TFA ingestion promotes obesity, decreases insulin sensitivity (10), and increases the risk of cardiovascular disease in the general population (11). Central obesity and insulin resistance can also be induced experimentally via ablation of the arcuate nucleus using neonatal administration of a high dose(s) of the food flavor enhancer monosodium glutamate (MSG) (12�C14).

The mechanism for this is believed to involve glutamate-induced degeneration of those areas of the immature brain that are insufficiently protected by a mature blood-brain barrier, including regions that regulate feeding and satiety (15). MSG consumption has increased globally in recent years, with recent GSK-3 estimations of the current average daily intake believed to be up to 10 g/day (16). In 1974, an acceptable daily intake for MSG was set at 0�C120 mg/kg body weight (bw) (17). In Europe, intake of MSG consumption is estimated as approximately 30 mg/kg bw (18), although in some countries, intake of MSG could be as high as 143 mg/kg bw (16).