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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Obesity

Intervention / Treatment
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* Drug: Intralipid, 20% Intravenous Emulsion
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-diabetic, normal weight individuals receiving Intralipid<br>Non-diabetic, normal weight individuals receiving Intralipid. Participants will receive an infusion of Intralipid 20% for 12 hours through an IV (prior to and during scan #2) | Drug: Intralipid, 20% Intravenous Emulsion<br>* Infusion of Intralipid 20%<br>|
| Placebo Comparator: Non-diabetic, normal weight individuals receiving saline<br>Non-diabetic, normal weight individuals receiving saline. Participants will receive an infusion of normal saline (1:1 randomization) at 30 ml/hr for 12 hours through an IV (prior to and during scan #2 | Drug: Placebos<br>* saline 30 ml/hr for 12 hours through an IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in brain glucose transport capacity | Measurement of brain glucose transport rates using magnetic resonance spectroscopy (MRS). | Through End of Study (Up to 12 hours) |