Neuroimmune Mechanisms in Obesity

Aim 1: To measure levels of microglia using the radiotracer \[11C\]PBR28 and PET brain imaging in obese (n=50) vs. lean individuals (n=50). The investigators will recruit 100 subjects who will participate in a single \[11C\]PBR28 scan to measure levels of TSPO, a marker of microglia.

Aim 2: To determine differences in brain functional connectivity at rest and in response to a decision- making task in obese (n=50) vs. lean individuals (n=50) using fMRI imaging. The same subjects from Aim 1 will participate in a resting state functional magnetic resonance imaging (fMRI) followed by a decision making task during fMRI acquisition.

Aim 3: To assess whether acute elevation of lipid levels through intralipid infusion in lean, healthy individuals (n=20) will induce microglial activation. 20 lean individuals will be recruited to participate in a paradigm that includes a baseline \[11C\]PBR28 scan, an infusion of intralipid, and a second \[11C\]PBR28 scan approximately 4 hours post intralipid infusion. The investigators will attempt to utilize subjects from aim 1 in order to use their baseline scans for this paradigm.

Aim 4: To determine whether there are differences in levels of microglia between individuals with and without type 1 diabetes (n=20). 20 patients with diabetes (type 1 diabetes or type 2 diabetes)will be recruited to participate in a single \[11C\]PBR28 scan to compare to Aim 1 participants.


Eligibility Criteria:
Inclusion Criteria:

* Age 18-55 years
* Able to read and write English and provide voluntary informed consent
* Physically and psychiatrically healthy by medical history, physical, psychiatric, neurological, EKG and laboratory examinations
* For Aims 1-3: HbA1C \< 5.7%
* For Aim 4: HbA1C \>6.5% and known diagnosis of T1DM or T2DM

Exclusion Criteria:

* Abnormal labs including Creatinine\>1.5mg/dL, Hematocrit \< 35% for females and \< 39% for males, ALT/AST \>2.5X upper limit of normal, abnormal TSH
* Known significant thyroid, hepatic, neurologic, psychiatric, cerebrovascular, or cardiovascular disease
* \>5% body weight change in last 6 months
* Current or recent regular steroid use in last 6 months, illicit drug use that is deemed to interfere with results including problematic alcohol use as defined by NIAAA
* Current regular use of psychotropic and/or potentially psychoactive prescription medications
* Regular use of any vitamins/supplements that could affect lipids
* Current regular use of non-steroidal anti-inflammatory medications, statins, or lipid lowering agents
* Vaccination in the last month
* Individuals who are classified as "low binders" for the rs6971 polymorphism (\<10% of the population)
* For females, physical or laboratory (-HCG) evidence of pregnancy, seeking pregnancy, or lactating. A urine drug screen and pregnancy test will be performed at screening and prior to the imaging session. Subjects who screen positive will be excluded.

Note: If a subject tests positive for an illicit substance, the PI will determine if the substance would interfere with the results and may terminate participation if applicable. Results of the test would only be noted in the subjects de-identified chart to document the occurrence.