Investigating Whether Acute Elevation of Fatty Acid Levels Alters Cerebral Glucose Transport and Metabolism

There are 2 aims of this study. The intent of aim 1 is to measure the effect of obesity on glucose transport and metabolism in the human brain. This study aim will be conducted in non-diabetic, obese individuals and age- and HbA1c-matched normal weight individuals. A total of 15 non-diabetic - normal weight individuals and 15 obese individuals will be enrolled.

The second aim randomizes 40 non-diabetic, normal weight individuals. The intent of aim 2 is to determine whether acute elevation of NEFA levels in lean, healthy individuals will alter cerebral glucose transport. Eligible participants will be randomized (1:1) to receive either intralipid or normal saline.

The focus of this protocol registration is the randomized portion of the study (aim 2).

Inclusion criteria

• Age 18-45 years
• HbA1C <6.5%
• Normal weight individuals: BMI 17-25 kg/m^2
• Obese individuals: BMI >30 kg/m^2

Exclusion criteria

• Creatinine >1.5mg/dL
• Hematocrit <35% for females and <39% for males
• ALT and AST >2.5X upper limit of normal
• Abnormal TSH
• Abnormal PT/PTT/INR
• Triglycerides >200 mg/dL
• Known hepatic, gastrointestinal, renal, neurologic, psychiatric, cerebrovascular disease
• Uncontrolled hypertension
• Current or past 3 months use of ketogenic diet
• Use of any medications, vitamins, or supplements that can alter cerebral metabolism or lipids
• Smoking
• Current or recent steroid use in last 6 months
• >5% body weight change in last 6 months
• Illicit drug use/alcoholism
• Inability to enter MRI/MRS
• For women: pregnancy, seeking pregnancy, or breastfeeding