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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
38
Administered orally once every 12 hours
Administered orally once every 12 hours
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran
Mexico City, Mexico
Insulin sensitivity
Measurement of insulin by an oral glucose tolerance test.
Time frame: Baseline to 2 months
Fecal microbiota
Composition, abundance and diversity of fecal microbiota by sequencing 16s rRNA gene
Time frame: Baseline to 2 months
Glucose metabolism profile
Serum glucose (mg/dL)
Time frame: Baseline to 2 months
Insulin (µUI/ml)
Serum insulin
Time frame: Baseline to 2 months
Triglycerides
serum triglycerides (mg/dL)
Time frame: Baseline to 2 months
Total cholesterol
serum total cholesterol (mg/dL)
Time frame: Baseline to 2 months
LDL cholesterol
serum LDL cholesterol (mg/dL)
Time frame: Baseline to 2 months
HDL cholesterol
serum HDL cholesterol (mg/dL)
Time frame: Baseline to 2 months
Antioxidant profile
Serum malondialdehyde (MDA) (nmol/mL)
Time frame: Baseline to 2 months
Body weight
body wight (kg)
Time frame: Baseline to 2 months
Blood pressure
blood pressure (mmHg)
Time frame: Baseline to 2 months
Change in PGC1α content
Measure of PGC1α protein content in skeletal muscle tissue taken by biopsy
Time frame: Through study completion, an average of 2 months
Change in AMPK content
Measure of AMPK protein content in skeletal muscle tissue taken by biopsy
Time frame: Through study completion, an average of 2 months
Succinate dehydrogenase
Fold change in succinate dehydrogenase activity in skeletal muscle tissue taken by biopsy
Time frame: Through study completion, an average of 2 months
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