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Oral awarded R01 grant for further research on leptin therapy in nonalcoholic steatohepatitis (NASH)

dr elif oralDr. Elif Oral

 

The aggressive form of fatty liver disease appears to reverse when patients are given the missing hormone

 

ANN ARBOR (June 2011) — Elif Oral, M.D., has been awarded her first R01 grant, from the National Institute of Diabetes, Digestive and Kidney Diseases of the National Institutes of Health. The grant project will study the effects of recombinant human leptin on nonalcoholic steatohepatitis (NASH), an aggressive form of nonalcoholic fatty liver disease.

Dr. Oral is Assistant Professor of Internal Medicine in the Metabolism, Endocrinology & Diabetes (MEND) Division, Department of Internal Medicine, as well as Director of the MEND Post-Bariatric Surgery Clinic and Medical Director of the UMHS Bariatric Surgery Program.

Obesity and insulin resistance afflict millions of Americans and can lead to many debilitating conditions, including nonalcoholic fatty liver disease (NAFLD). A more aggressive form of NAFLD is called nonalcoholic steatohepatitis (NASH), characterized by fatty inflammation of the liver in people who do not abuse alcohol.

NASH tends to occur especially in overweight men and women with insulin resistance. It is typically a chronic condition that causes no symptoms or very mild symptoms, and can sometimes cause progressive scarring and cirrhosis of the liver. "However, new research has shown that fatty liver disease may forecast future diabetes and/or cardiovascular disease, even if it does not progress to more severe liver disease," Dr. Oral states.

The fat cell hormone leptin is thought to play a role in preventing the accumulation of fat deposits in the liver, which is the first step in fatty liver disease. Approximately 20 percent of people who develop fatty liver disease don’t have enough leptin in their bodies. In 1997, Dr. Oral was one of the first researchers to become interested in the idea of supplying leptin to patients who are deficient, similar to how insulin is replaced in type 1 diabetes patients who cannot manufacture it in their own bodies.

Dr. Oral had success with this idea when she began treating lipodystrophy patients with recombinant human leptin therapy while at the National Institutes of Health in 2001–2002 and, in 2009, when she continued the project at the University of Michigan — making it the third medical center in the U.S. (and only the fourth in the world) to offer the leptin therapy for lipodystrophy.

Lipodystrophy is a rare metabolic disorder in which patients have low or nonexistent levels of leptin in their bodies. When given the leptin that their bodies are lacking, the lipodystrophy patients show dramatic and life-changing improvements.

Studies in human lipodystrophy and leptin deficiency indicate that supplying the missing leptin results in a decrease in cellular injury, in addition to reversing liver fat accumulation.

Dr. Oral’s R01 study will investigate how well recombinant leptin therapy works for patients with NASH, as well as for patients with relative leptin deficiency, against patients receiving a placebo. The study will also evaluate the long-term effects in patients who have been treated with recombinant leptin therapy in Dr. Oral’s prior pilot studies.

Patients will participate in the study for a period of one year. The project was awarded $1,250,000 for five years.

There are at least 5 million people in the US with NASH, and approximately 20% of these — 1 million Americans — demonstrate relative leptin deficiency, making them ideal candidates for restorative therapy with recombinant leptin. Thus, discovery of effective strategies to treat NASH could make a big impact on health-care costs in the US.