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. 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, IRS1, Akt, and ERK1/2) was impaired, whereas 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 that contribute to insulin resistance: HFr-associated increased expression and activity of NADPH oxidase, activation of redox-sensitive signals, expression of NF-κB-regulated proinflammatory 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 for defining interventions that can prevent/mitigate MetS-associated insulin resistance.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 247-256 |
| Number of pages | 10 |
| Journal | Free Radical Biology and Medicine |
| Volume | 72 |
| DOIs | |
| State | Published - 2014 |
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Keywords
- Endoplasmic reticulum stress
- Epicatechin and flavonoids
- Free radicals
- Insulin resistance
- Metabolic syndrome
- NADPH oxidase
- Redox signaling
ASJC Scopus subject areas
- Biochemistry
- Physiology (medical)
- Medicine(all)
Cite this
(-)-Epicatechin mitigates high-fructose-associated insulin resistance by modulating redox signaling and endoplasmic reticulum stress. / Bettaieb, Ahmed; Vazquez Prieto, Marcela A.; Rodriguez Lanzi, Cecilia; Miatello, Roberto M.; Haj, Fawaz; Fraga, César G.; Oteiza, Patricia I.
In: Free Radical Biology and Medicine, Vol. 72, 2014, p. 247-256.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - (-)-Epicatechin mitigates high-fructose-associated insulin resistance by modulating redox signaling and endoplasmic reticulum stress
AU - Bettaieb, Ahmed
AU - Vazquez Prieto, Marcela A.
AU - Rodriguez Lanzi, Cecilia
AU - Miatello, Roberto M.
AU - Haj, Fawaz
AU - Fraga, César G.
AU - Oteiza, Patricia I.
PY - 2014
Y1 - 2014
N2 - 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. 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, IRS1, Akt, and ERK1/2) was impaired, whereas 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 that contribute to insulin resistance: HFr-associated increased expression and activity of NADPH oxidase, activation of redox-sensitive signals, expression of NF-κB-regulated proinflammatory 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 for defining interventions that can prevent/mitigate MetS-associated insulin resistance.
AB - 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. 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, IRS1, Akt, and ERK1/2) was impaired, whereas 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 that contribute to insulin resistance: HFr-associated increased expression and activity of NADPH oxidase, activation of redox-sensitive signals, expression of NF-κB-regulated proinflammatory 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 for defining interventions that can prevent/mitigate MetS-associated insulin resistance.
KW - Endoplasmic reticulum stress
KW - Epicatechin and flavonoids
KW - Free radicals
KW - Insulin resistance
KW - Metabolic syndrome
KW - NADPH oxidase
KW - Redox signaling
UR - http://www.scopus.com/inward/record.url?scp=84901054689&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901054689&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2014.04.011
DO - 10.1016/j.freeradbiomed.2014.04.011
M3 - Article
C2 - 24746618
AN - SCOPUS:84901054689
VL - 72
SP - 247
EP - 256
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -