Fatty Liver
Conditions
Keywords
Non-Alcoholic Fatty Liver disease
Brief 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.
Interventions
DRUGRadio pharmaceuticals C-11 Acetate, and C-11 Palmitate
injection of C-11 Palmitate and C-11 Acetate during PET/CT to determine Liver metabolism
Sponsors
Barnes-Jewish Hospital
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Fatty Acid Oxidation | 3 hours | Liver fatty acid oxidation as determined by 1-11C-palmitate PET imaging. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Obese Females (Pre-bariatric Surgery) Twenty obese females (18-45 years of age, BMI \> or equal to 45) who are scheduled to undergo bariatric surgery at Barnes-Jewish Hospital will be screened for enrollment over 2 years. | 0 |
| Total | 0 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Hepatic Fatty Acid Oxidation
Liver fatty acid oxidation as determined by 1-11C-palmitate PET imaging.
Time frame: 3 hours
Population: The PI has left the institution, all efforts to locate the data have been exhausted and therefore no results are available to be reported.