Effect of the Bioactive Compounds Genistein and Resveratrol on Insulin Resistance in Patients with Metabolic Syndrome
Authors: Salas Einar Thor Godínez , Guevara‐Cruz Martha , Villanueva‐Luna Priscila , del Rocio Guizar‐Heredia Maria , Villalobos Gonzalo Manuel Torres , Ontiveros Edgar Pichardo , Nava Guillermo Ordaz , Villalvazo Ivan Torres , Torres Nimbe , Tovar Armando Roberto 
Published: November 2023

BackgroundObesity is a public health problem that has been linked to the development of insulin resistance (IR), which is defined as the inability of tissues to respond to the action of this hormone. The presence of IR is associated with lipotoxicity and a greater metabolic inflexibility. Experimental studies in rodents in our laboratory have shown that bioactive compounds (Resveratrol (R), Genistein (G)) can improve insulin sensitivity by the activation of AMPK in skeletal muscle (SM), increasing fatty acid oxidation. However, these has not been demonstrated in humans.ObjectiveTo demonstrate the effect of resveratrol and/or genistein on insulin sensitivity in subjects with metabolic syndrome (MetS) and IR, and its association with the activation of AMPK in SM.MethodsWith this aim we conducted a clinical trial, randomized, double blind, including Mexican mestizos men and women with overweight and obesity (age range: 20–60 yrs.), who satisfied 3 positive criteria for MetS. Before and after each intervention, a glucose tolerance test was performed to measure glucose and insulin. In addition, HDL‐C, LDL‐C, Triglycerides, leptin, and adiponectin were measured. Basal energy expenditure, oxygen consumption, and respiratory quotient were assessed by indirect calorimetry.Muscle biopsies were taken only from 20 patients after two months of consumption of any bioactive compound (Placebo (P), R, G, and Combination (C)). Subsequent to the biopsy, JAK2, AMPK, ACC and their phosphorylated forms were assessed by Western blot and a histological analysis with SDH staining was performed.ResultsForty‐two participants completed the study, in the genistein group there was a decrease in weight, BMI, waist circumference (WC), adiponectin, AUC of insulin, leptin and an increase in muscle mass. In the resveratrol group there was a decrease in WC, diastolic blood pressure, liver function tests, leptin, AUC of insulin and an increase in muscle mass. In the combination group there was a decrease in weight, BMI, AUC of glucose and insulin. However there were no statistical differences in the placebo group. In the muscle biopsy we observed an increase in pAMPK, pACC, pJAK2 and PGC1 alfa concentration as well as a higher mitochondrial density in the groups that consumed any of the bioactive compounds compared to placebo group.ConclusionConsumption of these bioactive compounds improved insulin sensitivity, and it was associated with the activation of the AMPK pathway. Therefore, our results suggest that genistein and resveratrol could be used as a preventive strategy to ameliorate the abnormalities of glucose metabolism in patients with MetS.Support or Funding InformationCONACYT GRANT 261843/UNAMSupported by Consejo Nacional de Ciencia y Teccnología. Grant s CONACyT 261843 to ATP and UNAM (National Autonomous University of Mexico)