Very Low Calorie Diet Weight Loss

The overarching hypothesis is that there are baseline, pre- and post-diet combinations of
'omics' signatures in response to food and nutrients that explain the weight loss response of
obese subjects to the very low calorie (VLC) diet.

In order to address the general hypothesis the following specific aims will be addressed:

Specific Aim 1: To test the hypothesis that there is a combination of 'omics' parameters in
response to a defined meal that discriminate between morbidly obese subjects.

Specific Aim 2: To test the hypothesis that variation in % weight loss to the 2-weeks of VLC
diet is related to baseline genomic markers, gene expression profile, proteomic and
metabolomic signatures as well as baseline metabolic and substrates fluxomics response to a
defined meal.

Specific Aim 3: To test the hypothesis that variation in % weight loss to the 4-weeks of VLC
diet is related to baseline genomic markers, gene expression profile, proteomic and
metabolomic signatures as well as baseline metabolic and substrates fluxomics response to a
defined meal.

Inclusion criteria obese subjects:

Diagnosed with morbid obesity (defined as BMI > 40 kg/m2 or BMI > 35 kg/m2 with at least
one serious comorbidity (2013 NIH compendium guidelines)) Scheduled for medically
supervised Very Low Calorie Diet Age 30 years and older Ability to lay in supine or
elevated position for 5 hours Willingness and ability to comply with the protocol Exclusion
Criteria Any condition that may interfere with the definition 'healthy subject' according
to the investigator's judgment (for healthy control group only) Participation in Weight
Loss Management Program within the last 6 months prior the first study day Presence of
fever within the last 3 days Untreated metabolic diseases including hepatic or renal
disorder unrelated to the primary disease Presence of acute illness or metabolically
unstable chronic illness unrelated to the primary disease

· (Possible) pregnancy Any other condition according to the PI or nurse that would
interfere with the study or safety of the patient Failure to give informed consent Use of
protein or amino acid containing nutritional supplements within 3 days of first test day