Omics Profiling of Weight Loss With Bariatric Surgery

Omics Profiling of the Response to Food and Variability of Weight Loss With Bariatric Surgery

Understanding how foods and nutrients are digested, absorbed and metabolized when weight is stable and during weight loss induced by bariatric surgery procedure using the technologies of genomics, transcriptomics, proteomics, metabolomics and fluxomics ("omics") will enable generation of new hypotheses that could explain the inter-individual differences in weight loss and could lead to optimization and individualization of therapies designed to lose weight.

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

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 and normal weight subjects.

Specific Aim 2: To test the hypothesis that variation in % weight loss to the VLC diet prior to bariatric surgery 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 2: To test the hypothesis that variation in % weight loss 3 months after bariatric surgery 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 whether there are "omics" characteristics post-surgery that track with variability in weight loss at 3 months.

The benefit of these experiments will be the knowledge gained from understanding the variation in % weight loss to the medically required VLC diet prior to bariatric surgery, and to bariatric surgery, in relation to baseline genomic markers, gene expression profile, proteomic and metabolomic signatures as well as baseline metabolic and substrates fluxomics response to a defined meal in obese and healthy adults.

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 (1991 NIH compendium guidelines))
• Scheduled for bariatric surgery
• Age 18 years and older
• Ability to lie in supine or elevated position for 9 hours
• Willingness and ability to comply with the protocol

Inclusion criteria healthy subjects:

• Healthy male or female according to the investigator's or appointed staff's judgment
• Ability to walk, sit down and stand up independently
• Age 18 years or older
• Ability to lie in supine or elevated position for 9 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)
• 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