U.S. Department of Health and Human Services

Clinical Research Section - Liver and Energy Metabolism Unit

Yaron Rotman, M.D., M.Sc., Chief

About the Unit

Generation of fat is an important mechanism for the body to store excess energy for future use. However, excess accumulation of fat, or deposition of fat in locations other than the adipose tissue, is associated with negative impact on health. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in the Western world, estimated to affect at least 30% of Americans, and is becoming a leading cause of liver-related suffering and death. It is commonly associated with obesity, diabetes, elevated blood lipids and the metabolic syndrome. At its core, NAFLD encompasses fat accumulation in the liver in response to excess nutrients, and in some patients also causes liver injury (non-alcoholic steatohepatitis - NASH), which can lead to progression of liver disease. Interestingly, different individuals will accumulate different amounts of fat in their liver and not all individuals with NAFLD will also develop the progressive form of NASH. The focus of our unit is to understand this variability in the response to excess energy by studying mechanisms of fat accumulation in the liver, genetic influences, the natural history and progression to injury. Our ultimate goal is to use this knowledge to identify interventions to treat NAFLD in individuals with the disorder and prevent it in those at risk.

Current Research

There are two groups of projects currently active in our unit:

  1. Through genetic studies we identified several genes that are implicated in the occurrence of NAFLD and its progression. We are utilizing molecular biology techniques, animal models and human tissue and blood samples to dissect the mechanism by which these genes affect fat metabolism in the liver, as well as understand their normal physiological role.
  2. Clinical studies that aim to understand the effect of interventions on NAFLD. Many studies in NAFLD and other disorders evaluate patients when they are at a stable, steady-state condition. Our unique approach has been to utilize short-term and long-term perturbations from steady-state to unmask information about the underlying mechanisms of disease. We are collecting specimens from liver, adipose tissue and blood, as well as using archived samples, and Current projects include:
    • Clinical trials that utilize blood tests or a breath test device to assess the response of patients with NAFLD and controls to a defined meal
    • A clinical trial to understand the mechanism of response of NAFLD patients to vitamin E treatment and to lifestyle changes.
    • Studies looking for biomarkers of response to treatment using archived samples from previous treatment trials.

We also collaborate with other investigators on studies where fat accumulation in the liver is the hepatic response to a genetic disorder or to medical treatment.

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