This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from fatty liver to non-alcoholic steatohepatitis (NASH). The pathogenesis for the progression of normal liver to hepatic steatosis to NASH is unknown, although insulin resistance and unopposed oxidative stress has been implicated. The purpose of this pilot study is to investigate for alterations in methionine metabolism in patients with hepatic steatosis and NASH, which may affect the antioxidant status in hepatocytes. Fifty obese, NAFLD patients between 25-60 years of age (25 with steatosis and 25 with NASH) with a BMI between 25-35 kg/m2 will be recruited. Twenty-five non-diabetic healthy volunteers of the same age group will serve as controls. After an overnight fast, an indwelling intravenous cannula (heparin lock) will be placed in a superficial vein of the forearm. Following a 30 minute rest period, a 1 mL blood sample will be drawn for the measurement of glucose and insulin. At 35 minutes, a 20 mL blood sample will be drawn for measurement of glucose, insulin, vitamin levels, a genetic polymorphism (MTHFR C677T), intermediates of methionine metabolism, and serum cytokine concentrations. At 40 minutes, 1 mL blood sample will be drawn for measurement of glucose and insulin. The groups will be compared for differences in these parameters in relation to insulin resistance, vitamin levels, presence of a genetic polymorphism, and alterations in methionine metabolism and cytokine concentrations. NAFLD is the most common chronic liver disease today. Understanding the etiopathogenesis is of utmost importance. The study proposed will provide preliminary data to clarify the mechanisms responsible for the development of NASH; specifically the role of methionine metabolism, which may provide the basis for the development of future treatment strategies.
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