INSULIN RESISTANCE IN NON-ALCOHOLIC STEATOHEPATITIS

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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 steatohepatitis (NASH) is a common liver disorder, characterized by histologic findings of steatosis, inflammation and fibrosis, that is strongly associated with obesity, diabetes, and dyslipidemia. Insulin resistance is an almost universal finding in patients with NASH and has been postulated to be causal in the accumulation of fat in the liver. NASH itself may also contribute to insulin resistance, possibly via the effects of inflammatory cytokines. Small pilot studies have shown benefit using treatments such as fibrates, which lower triglycerides; and the thiazolidinediones, which improve insulin sensitivity. However these studies have not investigated the relationships between hepatic steatosis, inflammation and hepatic and peripheral insulin sensitivity and the impact of treatment.