Effect of Diet Composition on Liver Fat and Glucose Metabolism

A condition called non-alcoholic steatohepatitis is characterized by fat accumulation in the
liver and associated inflammation. This condition is strongly associated with obesity,
insulin resistance and type 2 diabetes. Diets high in saturated fat result in fatty liver,
insulin resistance and liver injury in animal models. Dietary composition may contribute not
only to hepatic fat accumulation and insulin resistance but may also promote inflammation
leading to chronic liver disease in humans. This study will test the hypothesis that a diet
high in fat and saturated fat contributes to liver fat accumulation, insulin resistance and
inflammation by comparing the effects of a four-week, weight stable high fat/high saturated
fat diet (55% calories from fat/25% saturated fat) with a four-week, weight stable low
fat/low saturated fat diet (20% fat/8% saturated fat) in overweight and obese subjects.

Inclusion Criteria:

- Age 18-55 years old, men and women, otherwise in good general health, BMI >27 kg/m2

Exclusion Criteria:

- Abnormal glucose tolerance, fasting glucose>100 mg/dl or diabetes

- History of liver condition or alanine aminotransferase (ALT) above the upper limit of
the normal range

- Use of medications that cause insulin resistance or fatty liver: niacin,
glucocorticoids, estrogens, tamoxifen, amiodarone, accutane, sertraline, atypical
antipsychotics, anti-HIV medications

- Chronic use of anti-inflammatory medications (aspirin, ibuprofen, naprosyn, steroids,
etc)

- Average alcohol intake >20 grams/day

- Tobacco use

- Creatinine >1.5 mg/dl for men and >1.4 mg/dl for women

- Hematocrit <33%

- Pregnancy or lactation

- Significant weight loss within the past 6 months (>5% body weight)

- Claustrophobia or any contraindications to being placed in the magnet for the MRS
scan such as pacemakers, defibrillators, brain aneurysm clips, etc.

- Other serious medical conditions or inflammatory conditions such as cancer,
inflammatory arthritis, etc.

- History of multiple food allergies or intolerances or severe food allergies

- History of coronary artery disease, history of or treatment of hyperlipidemia, LDL
>200 mg/dl, fasting triglycerides >300 mg/dl

- Weight >300 pounds