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There is evidence that resveratrol can improve insulin resistance in rodents and humans with obesity and it can also improve muscle mitochondrial content mediated through activation of AMPK. However, little is known if this improvement is associated with changes in the gut microbiota and how gut microbiota is associated with serum metabolites after consumption of resveratrol. In the present study, the investigators show that the consumption of resveratrol for 2 months could influence insulin sensitivity in subjects with obesity. This effect will be accompanied by a modification of the microbiota taxonomy and the metabolites derived from this. Consequently, 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 mitochondrial biogenesis in skeletal muscle.
The investigators included 38 participants who met the following inclusion criteria: adults between 20 and 60 years of age with a diagnosis of HOMA-IR index greater than 2.5, and BMI ≥30 and ≤ 40 kg / m2 and who signed the consent letter. Participants 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 obesity. Participants were randomly distributed to consume a) placebo treatment or b) resveratrol capsules (150 mg/day). The participants were followed for 2 months. In the pre-randomization visit, informed consent letters were given, and blood samples were taken to evaluate glucose concentration, lipid profile and serum insulin, blood pressure, body weight and height and body composition. The presence of insulin resistance was determined by means of the HOMA-IR index. For the first visit body composition, other biochemical parameters such as protein c reactive, alanine transaminase, aspartate transaminase, hemoglobin glycosylated, hormones as leptin and adiponectin, free fatty acids in serum, malondialdehyde in serum, lipopolysaccharide in serum, short chain fatty acids in feces, fecal microbiota and serum metabolomics were determined. After 2 months, the same variables were assessed, and an expert surgeon in the operating room performed a vastus lateralis muscle biopsy, then protein extraction was performed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Resveratrol | Experimental | Resveratrol capsules of 75 mg each, 150 mg/day |
|
| Placebo | Placebo Comparator | Maltodextrin capsules, administered orally once every 12 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Resveratrol | Dietary Supplement | Administered orally once every 12 hours |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin sensitivity | Measurement of insulin by an oral glucose tolerance test. | Baseline to 2 months |
| Measure | Description | Time Frame |
|---|---|---|
| Fecal microbiota | Composition, abundance and diversity of fecal microbiota by sequencing 16s rRNA gene | Baseline to 2 months |
| Glucose metabolism profile | Serum glucose (mg/dL) |
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Inclusion Criteria:
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 gastrointestinal diseases.
Weight loss > 3 kg in the last 3 months.
Catabolic diseases such as cancer and acquired immunodeficiency syndrome.
Pregnancy status.
Antibiotic consumption 3 months prior to the study.
Be an undergraduate or graduate student within the Institute.
Positive smoking.
Drug treatment:
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| Name | Affiliation | Role |
|---|---|---|
| Armando R Tovar, Dr. | INCMNSZ | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran | Mexico City | Mexico |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000077185 | Resveratrol |
| ID | Term |
|---|---|
| D000081225 | Stilbestrols |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
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| Placebo |
| Dietary Supplement |
Administered orally once every 12 hours |
|
| Baseline to 2 months |
| Insulin (µUI/ml) | Serum insulin | Baseline to 2 months |
| Triglycerides | serum triglycerides (mg/dL) | Baseline to 2 months |
| Total cholesterol | serum total cholesterol (mg/dL) | Baseline to 2 months |
| LDL cholesterol | serum LDL cholesterol (mg/dL) | Baseline to 2 months |
| HDL cholesterol | serum HDL cholesterol (mg/dL) | Baseline to 2 months |
| Antioxidant profile | Serum malondialdehyde (MDA) (nmol/mL) | Baseline to 2 months |
| Body weight | body wight (kg) | Baseline to 2 months |
| Blood pressure | blood pressure (mmHg) | Baseline to 2 months |
| Change in PGC1α content | Measure of PGC1α protein content in skeletal muscle tissue taken by biopsy | Through study completion, an average of 2 months |
| Change in AMPK content | Measure of AMPK protein content in skeletal muscle tissue taken by biopsy | Through study completion, an average of 2 months |
| Succinate dehydrogenase | Fold change in succinate dehydrogenase activity in skeletal muscle tissue taken by biopsy | Through study completion, an average of 2 months |
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D059808 | Polyphenols |
| D010636 | Phenols |