The purpose of this study is to examine how acute nutritional challenges affect levels of several proteins involved in metabolism. These proteins will be measured in blood and fat tissue.

This study will have several aims.

One aim is to examine the effect of 72 hours of fasting on fibroblast growth factor-21 (FGF-21) levels. Participants will spend 3 days and nights in the Clinical Research Center at the Beth Israel Deaconess Medical Center in Boston, MA. Daily blood samples will be taken. Two fat samples will be taken prior to and at the end of the fast. A subset of participants will also have two MRIs, one prior to and one at the end of the fast. We will study healthy adults and obese adults with liver-biopsy-diagnosed non-alcoholic fatty liver disease (NAFLD). THIS STUDY ARM IS CURRENTLY NOT RECRUITING

Another aim is to examine the effect of low-calorie diet on FGF-21 levels. Subjects will follow a hypocaloric diet that will be designed to achieve 3-5% weight loss. We will enroll participants with liver-biopsy-diagnosed non-alcoholic fatty liver disease. Participants will report weekly to the Clinical Research Center at Beth Israel Deaconess Medical Center for weight measurements. Blood will be drawn before and after the weight loss. Participants will also have an MRI before and after the weight loss.

THIS ARM IS CURRENTLY NOT RECRUITING

Another aim of the study is to examine the effect of acute ingestion of glucose, fructose, and other sugars on serum FGF21 levels. Subjects in this study will be lean volunteers and individuals with metabolic syndrome.

THIS ARM IS CURRENTLY RECRUITING

Participation in this study involves fasting overnight, drinking a sweet beverage, and several blood draws through an IV line. Each subject may drink up to 5 different sweet beverages, separated by 2 weeks.

72-hour fast in healthy volunteers (Study Arm A):

Inclusion Criteria:

• Age 18-50 years
• Body Mass Index 21-26 kg/m^2
• Ability to give informed consent
• Ability to follow verbal and written instructions in English

Exclusion Criteria:

• Type 1 or Type 2 diabetes mellitus diagnosed according to the American Diabetes Association criteria

• Coronary heart disease (history of myocardial infarction, unstable angina pectoris, or congestive heart failure)

• Tobacco, marijuana, or intravenous drug use within 1 year of screening visit

• Recent weight change (>3 kg within 6 months of screening visit)

• Malignancy treated with chemotherapy within past 3 years

• History of depression, psychosis, or other psychiatric illness requiring hospitalization

• History of hyperthyroidism

• Renal insufficiency (creatinine clearance < 50 ml/min)

• Transaminases > 2X above the normal range

• Known liver disease

• Pregnancy within 12 months of screening visit

• Lactation within 12 months of screening visit

• Failure to use medically approved contraceptive methods (oral contraceptive, 2 barrier methods, surgical sterilization)

• History of an eating disorder (anorexia, bulimia, or laxative abuse)

• History of surgery for the treatment of obesity (gastric banding, gastric bypass, gastric stapling)

• New diagnosis of hypothyroidism within 1 year of screening visit or change in dose of thyroid hormone within 3 months of screening visit

• History of alcohol abuse within the past 3 years

• History of keloid formation

• History of allergy to lidocaine or marcaine

• Use of plavix, coumadin, or heparin

  72-hour fast or hypocaloric diet in subjects with non-alcoholic fatty liver disease (NAFLD) (Study Arms B & C):

Inclusion Criteria:

• Age 18-60
• BMI 25-45 kg/m^2
• Known nonalcoholic fatty liver disease based on liver biopsy
• Ability to give informed consent
• Ability to follow verbal and written instructions in English

Exclusion Criteria:

• Type I diabetes mellitus diagnosed according to the American Diabetes Association criteria or Type II diabetes mellitus with A1c > 7.5% or taking metformin or thiazolidinediones
• Coronary Heart Disease (history of myocardial infarction, unstable angina pectoris, or congestive heart failure)
• Uncontrolled hypertension (BP > 150/90 mmHg on or off antihypertensive medication)
• Tobacco, marijuana, or intravenous drug use within 1 year of screening visit
• Recent weight change (> 3 kg within 6 months of screening visit)
• Malignancy treated with chemotherapy within the past 3 years
• History of depression, psychosis, or other psychiatric illness requiring hospitalization
• History of hypo or hyperthyroidism
• Renal insufficiency (creatinine clearance < 50 ml/min)
• Pregnancy within 12 months of screening visit
• Lactation within 12 months of screening visit
• Failure to use medically approved contraceptive methods (oral contraceptive, 2 barrier methods, surgical sterilization)
• History of an eating disorder (anorexia, bulimia, or laxative abuse)
• History of surgery for the treatment of obesity (gastric banding, gastric bypass, gastric stapling)
• New diagnosis of hypo or hyperthyroidism within 1 year of screening visit or change in dose of thyroid hormone within 3 months of screening visit
• History of alcohol abuse within the past 3 years
• Cardiac pacemaker or aneurysm clips
• Metal implants in the body (pins, plates, shrapnel, intact bullets, IUD)
• Claustrophobia