Genistein Stimulates Insulin Sensitivity Through Gut Microbiota (GENISTEIN)

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: genistein; Dietary supplement: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: genistein; Genistein capsules of 25 mg each, 50mg/day	Dietary supplement: genistein; Administered orally once every 12 hours
Placebo Comparator: placebo; Maltodextrin capsules, administered orally once every 12 hours	Dietary supplement: Placebo; Administered orally once every 12 hours

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Collaborators: National Council of Science and Technology, Mexico

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2013
• Primary Completion (Actual): December 15, 2017
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: September 20, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Actual): September 26, 2019
• Last Update Submitted That Met QC Criteria: September 24, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: gut microbiota; genistein; fatty acid oxidation; AMPK
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Metabolic Syndrome; Insulin Resistance; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Estrogens, Non-Steroidal; Estrogens; Protein Kinase Inhibitors; Anticarcinogenic Agents; Phytoestrogens; Genistein
• Other Study ID Numbers: 1099

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No