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

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

The goal of this study is to understand the role of brain glucose transport in individuals with obesity and the association with cerebral hypometabolism and these individuals' response to plasma glucose elevations. The main premise is that obesity leads to reduced brain glucose transport and that we can measure this reduction with magnetic resonance spectroscopy (MRS). The secondary premises are that this reduction is driven by elevated non esterified fatty acids which act to turn on specific signaling pathways that regulate brain GLUT1 levels.

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