Liver Positron Emission Tomography (PET) Study of Non Alcoholic Fatty Liver Disease
Condition: Fatty Liver
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The purpose of this study is to evaluate how the liver receives and uses fats for energy.
      This will help the investigators further understand the physical and chemical processes
      responsible for Non-Alcoholic Fatty Liver Disease (NAFLD) in overweight females with or
      without NAFLD who are scheduled to undergo gastric bypass surgery.
    

Detailed description: 
      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.
    

Intervention name(s): Radio pharmaceuticals C-11 Acetate, and C-11 Palmitate
Intervention type(s): Drug
Intervention description(s): injection of C-11 Palmitate and C-11 Acetate during PET/CT to determine Liver metabolism
Intervention MeSH terms: Radiopharmaceuticals
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Non-Alcoholic Fatty Liver disease