Brain Gut Axis Changes After Bariatric Surgery and Their Relationship to Weight Loss

Brain Responses Associated With Ingestive Behavior in Obese Women: the Effects of Bariatric Surgery, and Their Association With Behavioral, Satiety Signal Responses and Weight Loss

Assessing the changes in the brain-gut axis after weight loss surgery and their relationship with weight loss and changes in eating behaviors.

Obese women undergoing weight loss surgery will be recruited to participate in the study. These individuals will undergo a screening visit and 4 study visits. The study visits will occur before, and at 1-, 6- and 12 months after the weight loss surgery. Each study visit will include evaluation of brain function (fMRI), anthropometrics, blood and stool samples and eating behaviors questionnaires.

Study Overview

• Status: Completed
• Conditions: Obesity; Bariatric Surgery Candidate
• Intervention / Treatment: Procedure: Bariatric surgery

Detailed Description

Assessing the changes in the brain-gut axis after weight loss surgery and their relationship with weight loss and changes in eating behaviors.

Obese women undergoing weight loss surgery will be recruited to participate in the study. These subjects will undergo a screening visit and 4 study visits. The study visits will occur before, and at 1-, 6- and 12 months after the weight loss surgery. Each study visit will include evaluation of brain function (fMRI), anthropometrics, blood samples (gut hormones, cytokines, metabolomics ) and stool samples (16S RNA and Metabolomics) and eating behaviors questionnaires (YFAS, TFEQ, food cravings/preferences scales, 3-day food food intake records)

Primary outcomes: weight loss after surgery and changes in eating behaviors scales (YFAS, TFEQ) , metabolomics, appetite related hormones and gut microbiome (16S RNA) Secondary outcomes: changes in brain function (fMRI/MRS), diet (3-day food intake records) and inflammatory markers.

• Study Type: Observational
• Enrollment (Actual): 22

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

We will include obese women undergoing bariatric surgery as part of standard medical care.

Description

Inclusion Criteria:

• Women, age 18-55 years
• Eligible and approved for undergoing laparoscopic gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) following the Guidelines for Clinical application of Laparoscopic Bariatric Surgery by of American Gastrointestinal and Endoscopic Surgeons (SAGES)
• Right-handed

Exclusion Criteria:

• Previous major gastrointestinal surgery including weight loss surgery (partial or complete resection of stomach and/or small bowel, Whipple procedure, etc)
• Use of medications known to affect hunger, satiety, or intestinal motility.
• Unwillingness or inability to give informed consent
• Any contraindication to undergo MRI
• Current or past alcohol or drug abuse problem or smoking
• Pregnancy, lactating or post partum less than 12 months
• Body weight at enrollment greater than 350 lbs.
• Current use of insulin and or insulin dependent diabetes
• Renal insufficiency, retinopathy, or neuropathy.
• Post menopausal (defined as no menses for 12 consecutive months)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of excess weight loss at 6 months	Measure of weight loss, it is calculated using the following formula: preoperative weight - weight at the follow-up visit)/(preoperative weight - Ideal body weight *100. Greater values mean greater weight loss (better).	Measured at 6-months after bariatric surgery
Percentage of excess weight loss at 12 months	Measure of weight loss, it is calculated using the following formula: preoperative weight - weight at the follow-up visit)/(preoperative weight - Ideal body weight *100. Greater values mean greater weight loss (better). Greater values are better.	Measured at 12-months after bariatric surgery
Change in Yale Food Addiction Scale score at 6 months	Yale Food Addiction Scale that is a 25-item measure developed to measure food addiction. Score range: 0 to 7. Higher scores in the scale mean more symptoms resembling food addiction (worse).	Measured at baseline and at 6-months after the bariatric surgery
Change in Yale Food Addiction Scale score at 12 months	Yale Food Addiction Scale that is a 25-item measure developed to measure food addiction. Score range: 0 to 7. Higher scores in the scale mean more symptoms resembling food addiction (worse).	Measured at baseline and at 12-months after the bariatric surgery
Change in Three-Factor Eating Questionnaire score at 6-months	Three-Factor Eating Questionnaire is a validated scale that is designed to measure 3 dimensions of human eating behavior: cognitive restraint of eating (Factor I), disinhibition (Factor II), and hunger (Factor III). The minimum score for factors I-II-III is therefore 0-0-0, and maximum possible score is 20-16-15. Higher scores in the respective scales are indicative of greater cognitive restraint (better), uncontrolled (worse), or emotional eating (worse).	Measured at baseline and 6-months after the bariatric surgery
Change in Three-Factor Eating Questionnaire score at 12-months	Three-Factor Eating Questionnaire is a validated scale that is designed to measure 3 dimensions of human eating behavior: cognitive restraint of eating (Factor I), disinhibition (Factor II), and hunger (Factor III). The minimum score for factors I-II-III is therefore 0-0-0, and maximum possible score is 20-16-15. Higher scores in the respective scales are indicative of greater cognitive restraint (better), uncontrolled (worse), or emotional eating (worse).	Measured at baseline and 12-months after the bariatric surgery
Change in diet (3-day food intake record) at 6-months.	3-day food intake record: individuals will record everything they eat and drink for 3 days. To assess calorie intake and macro nutrients	Measured at baseline and at 6-months after the bariatric surgery
Change in diet (3-day food intake record) at 12-months.	3-day food intake record: individuals will record everything they eat and drink for 3 days. To assess calorie intake and macro nutrients	Measured at baseline and at 12-months after the bariatric surgery
Changes in blood levels of Ghrelin at 6-months	Serum levels of Ghrelin. Units of gut hormones include Ghrelin in pg/ml. Enzyme-Linked Immunosorbent Assay to measure the levels of these hormones.	Measured at baseline and at 6-months after the bariatric surgery
Changes in blood levels of Ghrelin at 12-months	Serum levels of Ghrelin. Units of gut hormones include Ghrelin in pg/ml. Enzyme-Linked Immunosorbent Assay to measure the levels of these hormones.	Measured at baseline and at 12-months after the bariatric surgery
Changes in blood levels of glucagon-like peptide (GLP)-1 at 6-months	Serum levels of glucagon-like peptide (GLP)-1. Units of gut hormones include GLP-1 in pmol/L. Enzyme-Linked Immunosorbent Assay to measure the levels of these hormones.	Measured at baseline and at 6-months after the bariatric surgery
Changes in blood levels of glucagon-like peptide (GLP)-1 at 12-months	Serum levels of glucagon-like peptide (GLP)-1. Units of gut hormones include GLP-1 in pmol/L. Enzyme-Linked Immunosorbent Assay to measure the levels of these hormones.	Measured at baseline and at 12-months after the bariatric surgery
Changes in blood levels of Peptide YY at 6-months	Serum levels of peptideYY(PYY). Units of Peptide YY in pg/ml. Enzyme-Linked Immunosorbent Assay to measure the levels of these hormones.	Measured at baseline and at 6-months after the bariatric surgery
Changes in blood levels of Peptide YY at 12-months	Serum levels of peptideYY(PYY). Units of Peptide YY in pg/ml. Enzyme-Linked Immunosorbent Assay to measure the levels of these hormones.	Measured at baseline and at 12-months after the bariatric surgery
Changes in blood levels of insulin at 6-months	Serum levels of insulin. Units of gut hormones include insulin in ulu/L. Enzyme-Linked Immunosorbent Assay to measure the levels of these hormones.	Measured at baseline and at 6-months after the bariatric surgery
Changes in blood levels of insulin at 12-months	Serum levels of insulin. Units of gut hormones include insulin in ulu/L. Enzyme-Linked Immunosorbent Assay to measure the levels of these hormones.	Measured at baseline and at 12-months after the bariatric surgery
Changes in blood levels of leptin at 6-months	Serum levels of leptin. Units of gut hormones include Leptin in ng/ml. Enzyme-Linked Immunosorbent Assay to measure the levels of these hormones.	Measured at baseline and at 6-months after the bariatric surgery
Changes in blood levels of leptin at 12-months	Serum levels of leptin. Units of gut hormones include Leptin in ng/ml. Enzyme-Linked Immunosorbent Assay to measure the levels of these hormones.	Measured at baseline and at 12-months after the bariatric surgery
Changes in gut microbiome at 6 months	High-Throughput Microbiome Sequencing for sequencing of the 16S ribosomal RNA. Output sequences are classified as domain, phylum, family and genus to species, depending on the depth of reliable classifier assignments ribosomal RNA (rRNA) gene as the genetic marker to study bacterial phylogeny and taxonomy.	Measured at baseline and at 6-months after the bariatric surgery
Changes in gut microbiome at 12 months	High-Throughput Microbiome Sequencing for sequencing of the 16S ribosomal RNA. Output sequences are classified as domain, phylum, family and genus to species, depending on the depth of reliable classifier assignments ribosomal RNA (rRNA) gene as the genetic marker to study bacterial phylogeny and taxonomy.	Measured at baseline and at 12-months after the bariatric surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Brain function as measured by functional magnetic resonance imaging ( fMRI) at 6 months	Functional brain images will be obtained using established acquisition protocols for resting state and evoked brain responses	Measured at baseline and at 6-months after the bariatric surgery
Changes in Brain function as measured by functional magnetic resonance imaging ( fMRI) at 12 months	Functional brain images will be obtained using established acquisition protocols for resting state and evoked brain responses	Measured at baseline and at 12-months after the bariatric surgery
Changes in Inflammatory markers at 6 months	Serum levels of adipokines and inflammatory cytokines. Units include: Adiponectin in pg/ml, Interleukin 1β in pg/ml , Interleukin 6 in pg/ml, Lipopolysaccharide in pg/ml, tumor-necrosis-factor TNF-α in pg/ml. Enzyme-Linked Immunosorbent Assay to measure the levels of adipokines and inflammatory cytokines	Measured at baseline and at 6-months after the bariatric surgery
Changes in Inflammatory markers at 12 months	Serum levels of adipokines and inflammatory cytokines. Units include: Adiponectin in pg/ml, Interleukin 1β in pg/ml , Interleukin 6 in pg/ml, Lipopolysaccharide in pg/ml, tumor-necrosis-factor TNF-α in pg/ml. Enzyme-Linked Immunosorbent Assay to measure the levels of adipokines and inflammatory cytokines	Measured at baseline and at 12-months after the bariatric surgery
Changes in metabolite concentrations at 6 months.	Differences in blood metabolite concentrations measured by mass spectrometry, comparing metabolite concentrations from obese patients at baseline and after bariatric surgery.	Measured at baseline and at 6-months after the bariatric surgery
Changes in metabolite concentrations at 12 months.	Differences in blood metabolite concentrations measured by mass spectrometry, comparing metabolite concentrations from obese patients at baseline and after bariatric surgery.	Measured at baseline and at 12-months after the bariatric surgery

Collaborators and Investigators

• Sponsor: University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2014
• Primary Completion (Actual): April 15, 2021
• Study Completion (Actual): April 15, 2021

Study Registration Dates

• First Submitted: May 6, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Actual): August 16, 2021
• Last Update Submitted That Met QC Criteria: August 11, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Loss
• Other Study ID Numbers: IRB#13-001552

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No