Liver Positron Emission Tomography (PET) Study of Non Alcoholic Fatty Liver Disease

This study involves a multidisciplinary approach that will address the metabolic mechanisms
responsible for Non-alcoholic Fatty Liver Disease (NAFLD) in humans. Nonalcoholic fatty liver
disease (NAFLD) has become an important public health problem in many industrialized
countries because of its high prevalence, potential progression to severe liver disease, and
association with cardiometabolic abnormalities, including diabetes, the metabolic syndrome,
dilated cardiomyopathy, and coronary heart disease. Although obesity is an important risk
factor for NAFLD many obese persons have minimal or no steatosis. The mechanism responsible
for the pathogenesis of steatosis is not known, but must involve one or more of the
following:

1. Increased hepatic fatty acid (FA) delivery

2. Decreased hepatic FA oxidation

3. Increased de novo lipogenesis (DNL)

4. Inadequate hepatic triglyceride secretion

We hypothesize that alterations in all of these metabolic processes are involved in the
pathogenesis of NAFLD. However, a comprehensive evaluation of these factors in individual
cohorts of subjects has never been performed, and the ability to measure hepatic FA oxidation
in vivo in human subjects has not been available.

The following Specific Aims will be evaluated in obese women with and without NAFLD, who are
scheduled for bariatric surgery:

1. Determine hepatic FA uptake and oxidation by using novel PET techniques in combination
with measurements of DNL using stable isotope tracers and by assessing liver tissue FA
oxidative capacity by evaluating gene expression of FA oxidative enzymes and
mitochondrial content.

2. Determine hepatic fatty acid delivery by using stable isotope tracers to assess the rate
of free FA (FFA) release into plasma and cellular biology methods to determine the
expression and protein content of the major tissue FA transporter (CD36).

3. Determine hepatic very-low-density lipoprotein TG (VLDL-TG) secretion rate by using
stable isotope tracers.

4. Determine liver histology and factors involved in inflammation and fibrosis by using
routine staining and immunohistochemistry.

Inclusion Criteria:

- Obese females with a BMI of greater then or equal to 45.

- Age range between 18-45 years.

- Patients undergoing bariatric surgery at Barnes-Jewish Hospital-St.Louis,MO.

Exclusion Criteria:

- Any prior history or evidence of liver disease other than Non-Alcoholic Fatty liver
Disease, severe hypertriglyceridemia and diabetes mellitis.

- Consumed greater then or equal to 20 grams of alcohol per day.

- Taking medications that are known to cause hepatic steatosis & liver damage.