Reversal of insulin resistance in overweight and obese subjects by trans-resveratrol and hesperetin combination—link to dysglycemia, blood pressure, dyslipidemia, and low-grade inflammation
Author | Rabbani, Naila |
Author | Xue, Mingzhan |
Author | Weickert, Martin O. |
Author | Thornalley, Paul J. |
Available date | 2023-10-15T11:34:25Z |
Publication Date | 2021-07-11 |
Publication Name | Nutrients |
Identifier | http://dx.doi.org/10.3390/nu13072374 |
Citation | Rabbani, N., Xue, M., Weickert, M. O., & Thornalley, P. J. (2021). Reversal of insulin resistance in overweight and obese subjects by trans-resveratrol and hesperetin combination—link to dysglycemia, blood pressure, dyslipidemia, and low-grade inflammation. Nutrients, 13(7), 2374. |
Abstract | The dietary supplement, trans-resveratrol and hesperetin combination (tRES-HESP), induces expression of glyoxalase 1, countering the accumulation of reactive dicarbonyl glycating agent, methylglyoxal (MG), in overweight and obese subjects. tRES-HESP produced reversal of insulin resistance, improving dysglycemia and low-grade inflammation in a randomized, double-blind, placebo-controlled crossover study. Herein, we report further analysis of study variables. MG metabolism-related variables correlated with BMI, dysglycemia, vascular inflammation, blood pressure, and dyslipidemia. With tRES-HESP treatment, plasma MG correlated negatively with endothelial independent arterial dilatation (r = −0.48, p < 0.05) and negatively with peripheral blood mononuclear cell (PBMC) quinone reductase activity (r = −0.68, p < 0.05)—a marker of the activation status of transcription factor Nrf2. For change from baseline of PBMC gene expression with tRES-HESP treatment, Glo1 expression correlated negatively with change in the oral glucose tolerance test area-under-the-curve plasma glucose (∆AUGg) (r = −0.56, p <0.05) and thioredoxin interacting protein (TXNIP) correlated positively with ∆AUGg (r = 0.59, p < 0.05). Tumor necrosis factor-α (TNFα) correlated positively with change in fasting plasma glucose (r = 0.70, p < 0.001) and negatively with change in insulin sensitivity (r = −0.68, p < 0.01). These correlations were not present with placebo. tRES-HESP decreased low-grade inflammation, characterized by decreased expression of CCL2, COX-2, IL-8, and RAGE. Changes in CCL2, IL-8, and RAGE were intercorrelated and all correlated positively with changes in MLXIP, MAFF, MAFG, NCF1, and FTH1, and negatively with changes in HMOX1 and TKT; changes in IL-8 also correlated positively with change in COX-2. Total urinary excretion of tRES and HESP metabolites were strongly correlated. These findings suggest tRES-HESP counters MG accumulation and protein glycation, decreasing activation of the unfolded protein response and expression of TXNIP and TNFα, producing reversal of insulin resistance. tRES-HESP is suitable for further evaluation for treatment of insulin resistance and related disorders. |
Sponsor | - Unilever and Innovate UK (Project no 101129). - Qatar University - Qatar Foundation |
Language | en |
Publisher | Multidisciplinary Digital Publishing Institute (MDPI) |
Subject | Glyoxalase Insulin resistance Low-grade inflammation Methylglyoxal Obesity Polyphenol |
Type | Article |
Issue Number | 7 |
Volume Number | 13 |
ESSN | 2072-6643 |
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