Obesity
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTResveratrol
Administered orally once every 12 hours
DIETARY_SUPPLEMENTPlacebo
Administered orally once every 12 hours
Sponsors
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male and female. * Between 20 and 60 years * BMI ≥ 30 and ≤ 40 kg/m2 * Presence of insulin resistance (HOMA-IR index ≥ 2.5) * Willing and able to sign written informed consent prior to trial entry
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: * Antihypertensive drugs or treatment * Treatment with hypoglycemic agents or insulin and antidiabetic drugs. * Treatment with statins, fibrates or other drugs to control dyslipidemia. * Use of antibiotics in the three months prior to the study. * Use of steroid drugs, chemotherapy, immunosuppressants, or radiation therapy. * Anorexigenic or that accelerate weight loss such as sibutramine or orlistat. * Probiotic, prebiotic or symbiotic supplements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin sensitivity | Baseline to 2 months | Measurement of insulin by an oral glucose tolerance test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose metabolism profile | Baseline to 2 months | Serum glucose (mg/dL) |
| Insulin (µUI/ml) | Baseline to 2 months | Serum insulin |
| Triglycerides | Baseline to 2 months | serum triglycerides (mg/dL) |
| Total cholesterol | Baseline to 2 months | serum total cholesterol (mg/dL) |
| LDL cholesterol | Baseline to 2 months | serum LDL cholesterol (mg/dL) |
| HDL cholesterol | Baseline to 2 months | serum HDL cholesterol (mg/dL) |
| Fecal microbiota | Baseline to 2 months | Composition, abundance and diversity of fecal microbiota by sequencing 16s rRNA gene |
| Body weight | Baseline to 2 months | body wight (kg) |
| Blood pressure | Baseline to 2 months | blood pressure (mmHg) |
| Change in PGC1α content | Through study completion, an average of 2 months | Measure of PGC1α protein content in skeletal muscle tissue taken by biopsy |
| Change in AMPK content | Through study completion, an average of 2 months | Measure of AMPK protein content in skeletal muscle tissue taken by biopsy |
| Succinate dehydrogenase | Through study completion, an average of 2 months | Fold change in succinate dehydrogenase activity in skeletal muscle tissue taken by biopsy |
| Antioxidant profile | Baseline to 2 months | Serum malondialdehyde (MDA) (nmol/mL) |
Countries
Mexico
Outcome results
None listed