Fatty Liver and the Metabolic Syndrome

Brent A Neuschwander-Tetri


Curr Opin Gastroenterol. 2007;23(2) 

In This Article

Abstract and Introduction


Purpose of review: Nonalcoholic fatty liver disease and its subset nonalcoholic steatohepatitis represent the liver manifestations of insulin resistance. This review briefly summarizes advances in our understanding of the pathogenesis of nonalcoholic fatty liver disease and its prevalence, natural history and treatment.
Recent findings: The recognition of the role the renin-angiotensin system in promoting insulin resistance is worth noting because of available drugs. Endoplasmic reticulum stress has also become a recent target of investigation because endoplasmic reticulum stress is common in obesity, diabetes and various forms of liver disease including nonalcoholic fatty liver disease. Endoplasmic reticulum stress may be responsible for activation of c-Jun kinase, a process that may cause the hepatocellular injury in nonalcoholic steatohepatitis. Progress has also been made in estimating the prevalence of nonalcoholic fatty liver disease in adults and children. Patients enrolled in the Dallas Heart Study were found to have a 33% prevalence of nonalcoholic fatty liver disease and children dying of accidental deaths in San Diego were found to have a 13% prevalence of nonalcoholic fatty liver disease. Because about 10% of people with nonalcoholic fatty liver disease are at risk for progressive fibrosis, the burden of this disease is now quite substantial.
Summary: Incremental progress in understanding nonalcoholic fatty liver disease and nonalcoholic steatohepatitis promises to lead to new therapeutic options for this common disease.


Obesity is now recognized as a major challenge to health, quality of life and longevity in the developed world. The adverse impact of overweight and obesity on the risks for cardiovascular disease, cancer and musculoskeletal disorders is well documented, especially when coupled with components of the metabolic syndrome. More recently recognized is the risk of developing end stage liver disease and hepatocellular cancer as a consequence of nonalcoholic fatty liver disease (NAFLD), the primary hepatic complication of obesity and insulin resistance. Although NAFLD has not been included as a component of the metabolic syndrome as it has been defined, available data indicate that the onset of NAFLD is an early event in the development of insulin resistance and might thus predict the presence or future development of the metabolic syndrome. The purpose of this review is to selectively examine important studies published over the past year that provide new insights into the pathogenesis of NAFLD, its prevalence and its management.


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