A Role for FGF21 in Postprandial Nutrient Homeostasis After RYGB

Study Overview
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Brief Summary
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Bariatric surgery markedly improves glycemic control in persons with Type 2 Diabetes (T2D). Roux-en-Y gastric bypass (RYGB), a procedure that bypasses the upper gastrointestinal (UGI) tract, results in greater rates of diabetes resolution compared to methods that leave the UGI tract intact. Studies suggest that mechanisms beyond weight-loss account for the superiority of RYGB compared to other surgical methods. These weight-loss independent metabolic effects may involve increased postprandial production and release of nutrition- responsive hormones. Fibroblast growth factor 21 (FGF21) is a nutrition-adaptive hormone with the potential to alleviate symptoms of diabetes and obesity. Preliminary data therefore suggest that RYGB surgery may alter postprandial FGF21 regulation which could be important for achieving post-meal nutrient homeostasis. Therefore, the goal of this study is to test how nutrient content of the meal affects FGF21 concentrations before and after weight loss induced by RYGB or very low calorie diet (VLCD) therapy. The importance of FGF21 for glucose, insulin, triglyceride, and adipose tissue and muscle metabolism in these two groups will also be tested.

Official Title
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A Role for FGF21 in Postprandial Nutrient Homeostasis After RYGB

Conditions
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Obesity

Intervention / Treatment
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* Procedure: Roux-en-Y gastric bypass surgery
* Behavioral: Very low-calorie diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Surgery Group (RYGB): Males and Females Scheduled for RYGB surgery Body Mass Index 35-55 kg/m² Without Type 2 Diabetes (T2D) VLCD group: Males and Females Body Mass Index 35-55 kg/m² Without Type 2 Diabetes (T2D) Exclusion Criteria: Surgery Group (RYGB): Regular use of tobacco products Previous intestinal resection Pregnant or breastfeeding Evidence of significant organ system dysfunction or disease other than obesity and T2D Use of any medication that might, in the opinion of the investigator, affect metabolic function Exercise ≥90 minutes per week Use or past use of hormone replacement therapy within the past 6 months VLCD Group: Regular use of tobacco products Previous intestinal resection Pregnant or breastfeeding Evidence of significant organ system dysfunction or disease other than obesity and T2D Use of any medication that might, in the opinion of the investigator, affect metabolic function Exercise ≥90 minutes per week Use or past use of hormone replacement therapy within the past 6 months

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RYGB group<br>Subjects in this group are scheduled to undergo Roux-en-Y gastric bypass surgery and will be assessed after 16-18% weight-loss | Procedure: Roux-en-Y gastric bypass surgery<br>* A bariatric surgery procedure which will help individuals achieve 16-18% weight loss<br>|
| Active Comparator: VLCD Group<br>Subjects in this group will participate in a very low-calorie diet intervention to obtain a 16-18% weight loss. | Behavioral: Very low-calorie diet<br>* Subjects will meet with a dietitian and/or behaviorist over 4-6 months to lose 16-18% of their body weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial FGF21 plasma concentrations | Concentrations of FGF21 protein will be measured in plasma after consuming a high glucose meal or a high fat meal, before and after surgery or low calorie diet. | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Roux-en-Y gastric bypass (RYGB), Very low calorie diet, Fibroblast growth factor 21 (FGF21)