FGF21 and Fructose Challenge in Humans

Inclusion criteria for lean subjects: * Men and women ages 18-60 * BMI 19-25 kg/m2; 19-23 for Asian subjects * Stable weight (variation \< 3 kg within 6 months of screening visit) * Ability to give informed consent * Ability to follow verbal and written instructions in English * Use of medically approved form of contraception (monophasic oral contraception, intra uterine device, surgical sterilization or 2 combined barrier methods) Specific exclusion criteria for lean subjects: * Fasting blood glucose \>100; 2 hr OGTT blood glucose \>140 * Fasting triglycerides \>150 Inclusion criteria for metabolic syndrome subjects: 3 or more of the following (based on joint scientific statement by Alberti et al, 2009: * Fasting triglycerides \>150 mg/dl (or on treatment for elevated triglycerides) * HDL cholesterol \<40 mg/dl in men or \<50 mg/dl in women * Blood pressure \> 130/85 (or antihypertensive treatment in a subject with history of hypertension) * Fasting BG \>100 * Elevated waist circumference \*\* see below for race and ethnic specifications Men Women * Asian or Central, South or Native American \> 90 cm \> 80 cm * Non-Asian, Non-Latino United States \> 102 cm \> 88 cm General Exclusion criteria * Type 1 or type 2 diabetes mellitus diagnosed according to American Diabetes Association criteria * Coronary heart disease (history of myocardial infarction, unstable angina pectoris, or congestive heart failure) * Uncontrolled hypertension (BP \> 160/100 mmHg on or off antihypertensive medication) * Marijuana or intravenous drug use * Recent weight loss (\> 3 kg within 6 months of the screening visit) * Gastroparesis * Inflammatory or irritable bowel disease * Malignancy treated with chemotherapy within the past 3 years * Depression or psychosis requiring hospitalization * Renal insufficiency (creatinine clearance \< 40 ml/min) * Transaminases \> 2x above the normal range * Known liver disease * Pregnancy within 6 months of the screening visit * Lactation * Failure to use medically approved contraceptive methods * History of surgery for the treatment of obesity (gastric banding, gastric bypass, gastric stapling) * Change in dose of thyroid hormone or antithyroidal medication within 3 months of screening visit * History of alcohol abuse within the past 5 years * Fructose intolerance Exclusionary medications: * Oral steroids * Metformin * Weight loss medications including nonprescription supplements