(−)-Epicatechin mitigates high-fructose-associated insulin resistance by modulating redox signaling and endoplasmic reticulum stress

Abstract

We investigated the capacity of dietary (-)-epicatechin (EC) to mitigate insulin resistance through the modulation of redox-regulated mechanisms in a rat model of metabolic syndrome (MetS). Adolescent rats were fed a regular chow diet without or with high fructose (HFr) (10% (w/v)) in drinking water for 8 weeks, and a group of HFr-fed rats was supplemented with EC in the diet. HFr-fed rats developed insulin resistance which was mitigated by EC supplementation. Accordingly, the activation of components of the insulin signaling cascade (insulin receptor (IR), IRS-1, Akt and ERK1/2) was impaired, while negative regulators (PKC, IKK, JNK and PTP1B) were upregulated in the liver and adipose tissue of HFr rats. These alterations were partially or totally prevented by EC supplementation. In addition, EC inhibited events which contribute to insulin resistance: HFr-associated increased expression and activity of NADPH oxidase, activation of redox-sensitive signals, expression of NF-κB-regulated pro-inflammatory cytokines and chemokines, and some sub-arms of endoplasmic reticulum stress signaling. Collectively, these findings indicate that EC supplementation can mitigate HFr-induced insulin resistance and are relevant to define interventions that can prevent/mitigate MetS-associated insulin resistance.

Stachyose combined with tea polyphenols mitigated metabolic disorders in high fructose diet-fed mice as studied by GC-MS metabolomics approach

“…Our data also showed that HF diet caused a significant increase in serum β-hydroxybutyric acid level. A large number of studies have shown that long-term intake of HF can not only induce the occurrence of hepatic injury but also lead to severe insulin resistance (Bettaieb et al, 2014;Ren et al, 2014). Accordingly, the current metabolomics study based on the level of β-hydroxybutyrate acid confirmed once again that the long-term intake of HF led to insulin resistance.…”

“…Accordingly, the current metabolomics study based on the level of β-hydroxybutyrate acid confirmed once again that the long-term intake of HF led to insulin resistance. However, tea polyphenols, such as epicatechin and so on, can effectively improve fructose-induced insulin resistance by regulating redox signals and endoplasmic reticulum stress (Bettaieb et al, 2014). In this study, it has been found that tea polyphenols can effectively reduce the level of serum markers of β-hydroxybutyrate acid.…”

“…HF-induced liver injury is a typical metabolic syndrome, which is characterized by small molecules metabolites disorders (Bettaieb et al, 2014;Graziano et al, 2015). Routine biochemical analysis revealed that the combination of stachyose and tea polyphenol could effectively prevent HF-induced liver injury, but the mechanism of metabolic regulation is still not clear .…”

“…There is no doubt that tea polyphenols are effective in inhibiting the increase of trans-fatty acids in HF-fed mice. It may be due to the strong free radical scavenging and antioxidant activity of tea polyphenols (Bettaieb et al, 2014;Hung et al, 2016). More interestingly, the administration of stachyose together with tea polyphenols could more effectively inhibit the increase of serum anti-oleic acid levels in HF-fed mice than stachyose alone or tea polyphenols alone.…”

The role of p38 MAPK in the induction of intestinal inflammation by dietary oxysterols: modulation by wine phenolics

“…37 Modulation of the red-ox balance with down-regulation of NOX activity by epicatechin and its metabolites, preventing inflammatory processes, have been observed in both in-vivo and in-cell models, including intestinal ones. 38,39,20 Recently, the biological effects of flavanols have attracted great interest in gastrointestinal release studies for nutraceutical applications: niosome carriers have recently been used to enhance the uptake and transport of (+)-epicatechin and (-)-epigallocatechin gallate in CaCo-2 cells. 40 The majority of studies on caffeic acid in wine have concerned its quantification in different wine types, and have tested its antioxidant capacity.…”