Clinical trial NCT04105023: Genistein Stimulates Insulin Sensitivity Through Gut Microbiota
Official title: Genistein Stimulates Insulin Sensitivity Through Gut Microbiota Reshaping and Skeletal Muscle AMPK Activation in Obese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Obesity
Keywords: genistein
gut microbiota
AMPK
fatty acid oxidation
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
Collaborators: name: National Council of Science and Technology, Mexico
First posted: 2019-09-26
Enrollment: 45
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: intestinal microbiota
timeFrame: Baseline to 2 month
Secondary outcomes:
measure: glucose metabolism profile
timeFrame: Baseline to 2 month
measure: Glucose metabolism profile
timeFrame: Baseline to 2 month
measure: Triglycerides
timeFrame: Baseline to 2 month
measure: Total Cholesterol
timeFrame: Baseline to 2 month
measure: LDL cholesterol
timeFrame: Baseline to 2 month
measure: HDL cholesterol
timeFrame: Baseline to 2 month
measure: Inflammatory profile
timeFrame: Baseline to 2 month
measure: Body weight
timeFrame: Baseline to 2 month
measure: Blood pressure
timeFrame: Baseline to 2 month
Other outcomes:
Locations:
Study officials:
References:
citation: Guevara-Cruz M, Flores-Lopez AG, Aguilar-Lopez M, Sanchez-Tapia M, Medina-Vera I, Diaz D, Tovar AR, Torres N. Improvement of Lipoprotein Profile and Metabolic Endotoxemia by a Lifestyle Intervention That Modifies the Gut Microbiota in Subjects With Metabolic Syndrome. J Am Heart Assoc. 2019 Sep 3;8(17):e012401. doi: 10.1161/JAHA.119.012401. Epub 2019 Aug 27.
citation: Palacios-Gonzalez B, Vargas-Castillo A, Velazquez-Villegas LA, Vasquez-Reyes S, Lopez P, Noriega LG, Aleman G, Tovar-Palacio C, Torre-Villalvazo I, Yang LJ, Zarain-Herzberg A, Torres N, Tovar AR. Genistein increases the thermogenic program of subcutaneous WAT and increases energy expenditure in mice. J Nutr Biochem. 2019 Jun;68:59-68. doi: 10.1016/j.jnutbio.2019.03.012. Epub 2019 Mar 29.
citation: Lopez P, Sanchez M, Perez-Cruz C, Velazquez-Villegas LA, Syeda T, Aguilar-Lopez M, Rocha-Viggiano AK, Del Carmen Silva-Lucero M, Torre-Villalvazo I, Noriega LG, Torres N, Tovar AR. Long-Term Genistein Consumption Modifies Gut Microbiota, Improving Glucose Metabolism, Metabolic Endotoxemia, and Cognitive Function in Mice Fed a High-Fat Diet. Mol Nutr Food Res. 2018 Aug;62(16):e1800313. doi: 10.1002/mnfr.201800313. Epub 2018 Jul 29.
citation: Medina-Vera I, Sanchez-Tapia M, Noriega-Lopez L, Granados-Portillo O, Guevara-Cruz M, Flores-Lopez A, Avila-Nava A, Fernandez ML, Tovar AR, Torres N. A dietary intervention with functional foods reduces metabolic endotoxaemia and attenuates biochemical abnormalities by modifying faecal microbiota in people with type 2 diabetes. Diabetes Metab. 2019 Apr;45(2):122-131. doi: 10.1016/j.diabet.2018.09.004. Epub 2018 Sep 25.