ER Stress in NAFLD



Status:Not yet recruiting
Conditions:Obesity Weight Loss
Therapuetic Areas:Endocrinology
Healthy:No
Age Range:30 - 60
Updated:10/19/2013
Start Date:October 2013
End Date:April 2018
Contact:Charles R Flynn, PhD
Email:robb.flynn@vanderbilt.edu
Phone:615-343-8329

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Phospholipid Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease


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.


Inclusion Criteria:

- Ambulatory females age 30-60 years old

- Women of all ethnic groups

- BMI≥35 kg/m2

- Approval for Roux-en-Y gastric bypass or sleeve gastrectomy.

Exclusion Criteria:

- Smoking >7 cigarettes per day

- Previous malabsorptive or restrictive intestinal surgery

- Pregnant or breastfeeding

- Recent history of neoplasia (<5 years ago)

- Malabsorptive syndromes

- Inflammatory intestinal disease

- Patients with established organ dysfunction

- Diagnosis of type 1 or type 2 diabetes mellitus or current use of anti-diabetic
medication (last 30 days; last 60days for thiazolidinediones)

- Diagnosed hyperbetalipoproteinemia or hypobetalipoproteinemia

- Patients on cholesterol lowering medicines

- Vegan diet

- Hepatic fat content <10% by MRI

- Inability to comply with study protocol such as unable to make study visits or be
available daily for phone contact

- Any condition which would interfere with MRI or PET studies, e.g. claustrophobia,
cochlear implant, chronic back pain limiting ability to lay flat, metal fragments in
eyes, cardiac pacemaker, neural stimulator, tattoos with iron pigment and metallic
body inclusions or other metal implanted in the body which may interfere with MRI
scanning.
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1211 Medical Center Dr
Nashville, Tennessee 37232
(615) 322-5000
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