NONALCOHOLIC STEATOHEPATITIS (NASH): IS LEPTIN AN ETIOLOGICAL FACTOR (PHASE 1)

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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. Being overweight impairs the action of the insulin hormone, the primary hormone responsible from controlling sugar levels in the body. This is called a state of insulin resistance. Insulin resistance is commonly seen in patients who have fat accumulation in their liver. About 10% of patients with fat accumulation in their liver develop scarring that can lead to failure of liver and death. Another factor that has been shown in research studies to play a role in preventing fat accumulation in the liver is the leptin hormone, a hormone secreted by the fat cells. Previously we have observed very low leptin hormone concentrations in an unusual group of patients with abnormal body fat. In this group, there was marked fat accumulation and scarring in the liver as well as very severe insulin resistance. Both the liver problem and the insulin resistance remarkably reversed when we administered leptin hormone and achieved near normal leptin levels in these patients for about 4 months. These results made us wonder whether leptin hormone plays a role in the fat accumulation and scarring process in other patients with this condition. However, knowledge about the variation of leptin hormone levels and body composition and how these relate to each other and insulin resistance is lacking. In this study, we would like to determine the variation in body fat distribution and blood chemistry in patients known to have fat accumulation and scarring in their liver. We also would like to know how blood chemistry and body fat distribution in these patients affect the circulating leptin concentrations. This study comprises of one day of testing that involves baseline blood work, imaging studies that help to determine body fat distribution and a test that lasts three hours to determine how effective insulin is working in the cells. We will perform these studies on 50 patients with known fat accumulation and scarring. We will use this information to determine if we can develop new therapies to reverse or slow down fat accumulation and scarring in the liver.