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The study was not funded
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The investigators overall hypothesis is that exacerbation of endoplasmic reticulum (ER) stress in the liver is associated with significant alterations in phosphatidylcholines that drive the NASH phenotype in obese humans. The investigators plan to examine this hypothesis in a well-characterized cohort of obese subjects that are scheduled for bariatric surgery. Methyl-D9-choline chloride will be infused before and after a 2-week high fructose or glucose feeding to determine the biosynthesis and kinetics of secretory lipoprotein phospholipids. It is proposed that phospholipid metabolism play an important role in the pathogenesis or etiology of fatty liver in non-alcoholic conditions through mechanisms that invoke ER and oxidative stress responses.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fructose | Experimental | Participants will receive fructose (3g/kg/day) for 2 weeks. |
|
| Glucose | Active Comparator | Participants will receive glucose (3g/kg/day) for 2 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| methyl-D9-choline | Drug | Subjects in both arms will be infused with methyl-D9-choline in order to assess the biosynthesis and kinetics of secretory lipoprotein phospholipids. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Net hepatic phospholipid production | Net hepatic phospholipid production will be determined using [11C]choline dynamic Positron Emission Tomography (PET) before and after high fructose feeding for two weeks. A similar group of control obese subjects will undergo the same procedures before and after two weeks isocaloric glucose feeding. | Baseline and 2 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Kinetics of secretory lipoprotein phospholipids | The biosynthesis and kinetics of secretory lipoprotein phospholipids will be determined using methyl-D9-choline chloride infusion before and after high fructose (or glucose) feeding. | Baseline and 2 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in zonation of phospholipids and PEMT in liver tissues | Changes in zonation of phospholipids and PEMT in liver tissues acquired from the same subjects intraoperatively during bariatric surgery will be assessed using MALDI-IMS. | 60 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Charles R Flynn, PhD | Vanderbilt University Medical Center | Principal Investigator |
| Naji N Abumrad, MD | Vanderbilt University Medical Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D065626 | Non-alcoholic Fatty Liver Disease |
| D005234 | Fatty Liver |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |