Genistein Stimulates Insulin Sensitivity Through Gut Microbiota

Study Overview
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Brief Summary
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There is evidence that genistein present in soy can improve insulin resistance in rodents and humans with metabolic syndrome (MetS). However, it is not known if this improvement is associated with changes in the gut microbiota. In the present study, the investigators show that the consumption of genistein for 2 months could have an effect on insulin resistance in subjects with MetS. This effect will be accompanied by a modification of the gut microbiota taxonomy. As a consequence, there will be a reduction in metabolic endotoxemia accompanied by an increase in AMP-activated protein kinase (AMPK) phosphorylation and the expression of genes of fatty acid oxidation in skeletal muscle.

Detailed Description
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The investigators included 45 participants who met the following inclusion criteria: adults between 20 and 60 years of age with a diagnosis of MetS, HOMA index greater than 2.5, BMI ≥30 and ≤ 40 kg / m2 and who signed the consent letter. Patients who had any added pathology, pregnancy, smoking or consumed medications were excluded. Once the letter of informed consent was accepted, the patients were assigned to the respective treatment group. These individuals were advised to consume the recommended diet for subjects with MetS according to the guidelines of the ATPIII. Participants were randomly distributed to consume a) placebo treatment or b) genistein capsules (50 mg/day). The participants were followed for 2 months. In the previsit, informed consent letters were given, and blood samples were taken to evaluate glucose concentration, lipid profile, lipopolysaccharide and serum insulin. Also determined blood pressure, body weight, height, body composition and gut microbiota. The presence of insulin resistance was determined by means of the HOMA-IR index and by an oral glucose tolerance test. After 2 months, the same variables were assessed, and an expert surgeon in the operating room performed a vastus lateralis muscle biopsy, then RNA extraction and gene expression microarray assay was performed

Official Title
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Genistein Stimulates Insulin Sensitivity Through Gut Microbiota Reshaping and Skeletal Muscle AMPK Activation in Obese Subjects

Conditions
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Metabolic Syndrome, Obesity

Intervention / Treatment
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* Dietary Supplement: genistein
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (men and women) between the ages of 18 and 50. Patients with obesity (BMI ≥ 30 and ≤ 40 kg / m2) and with insulin resistance (HOMA - IR Index ≥ 2.5). Mexican mestizos (parents and grandparents born in Mexico). Patients who can read and write. Exclusion Criteria: • Patients with any type of diabetes. Patients with kidney disease diagnosed by a medical or with creatinine> 1.3 mg / dL for men and > 1.1 mg / dL for women and / or BUN> 20 mg / dL. Patients with acquired diseases that produce obesity and diabetes secondarily. Patients who have suffered a cardiovascular event. Patients with weight loss > 3 kg in the last 3 months. Patients with any catabolic diseases. Gravidity status Positive smoking Treatment with any medication

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: These individuals were advised to consume the recommended diet for subjects with MetS according to the guidelines of the ATPIII. Patients were randomly distributed to consume a) placebo treatment or b) genistein capsules (50 mg/day). The participants were followed for 2 months
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: genistein<br>Genistein capsules of 25 mg each, 50mg/day | Dietary Supplement: genistein<br>* Administered orally once every 12 hours<br>|
| Placebo Comparator: placebo<br>Maltodextrin capsules, administered orally once every 12 hours | Dietary Supplement: Placebo<br>* Administered orally once every 12 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intestinal microbiota | Measurement of gut microbiota by sequencing using the Illumina platform | Baseline to 2 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glucose metabolism profile | serum glucose (mg/dL) | Baseline to 2 month | 
| Glucose metabolism profile | serum insulin (µUI/ml) | Baseline to 2 month | 
| Triglycerides | serum triglycerides (mg/dL) | Baseline to 2 month | 
| Total Cholesterol | serum total cholesterol (mg/dL) | Baseline to 2 month | 
| LDL cholesterol | serum LDL cholesterol (mg/dL) | Baseline to 2 month | 
| HDL cholesterol | serum HDL cholesterol (mg/dL) | Baseline to 2 month | 
| Inflammatory profile | plasma lipopolysaccharide (LPS) (ng/mL) | Baseline to 2 month | 
| Body weight | body weight (kg) | Baseline to 2 month | 
| Blood pressure | blood pressure (mmHg) | Baseline to 2 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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genistein, gut microbiota, AMPK, fatty acid oxidation