(-)-Epicatechin improves insulin sensitivity in high fat diet-fed mice

Abstract

Obesity constitutes a major public health concern, being frequently associated with type 2 diabetes (T2D). Evidence from studies in humans and experimental animals suggest that consumption of the flavan-3-ol (−)-epicatechin (EC) and of EC-rich foods may improve insulin sensitivity. To further understand the potential benefits of dietary EC consumption on insulin resistance, this study investigated the capacity of EC supplementation to prevent high fat diet (HFD)-induced insulin resistance in mice. To assess the underlying mechanisms, the effects of HFD and EC consumption on the activation of the insulin cascade and of its negative modulators were evaluated. HFD consumption for 15 w caused obesity and insulin resistance in C57BL/6J mice as evidenced by high fasted and fed plasma glucose and insulin levels, and impaired ITT and GTT tests. This was associated with alterations in the activation of components of the insulin-triggered signaling cascade (insulin receptor, IRS1, ERK1/2, Akt) in adipose and liver tissues. EC supplementation prevented/ameliorated all these parameters. EC acted improving insulin sensitivity in the HFD-fed mice in part through a downregulation of the inhibitory molecules JNK, IKK, PKC and protein tyrosine phosphatase 1B (PTP1B). Thus, the above results suggest that consumption of EC-rich foods could constitute a dietary strategy to mitigate obesity-associated insulin resistance.

Anti-inflammatory actions of (−)-epicatechin in the adipose tissue of obese mice

“…We previously demonstrated that EC supplementation can protect rats from insulin resistance by high fructose consumption (Bettaieb et al, 2014) and by the consumption of a HFD in mice (Cremonini et al, 2016). In both conditions EC caused a major improvement in adipose tissue insulin sensitivity which was affected by chronic consumption of excess energy (as fructose or fat).…”

“…EC supplementation mitigates systemic and adipose tissue insulin resistance in a mouse model of HFD-induced obesity and insulin resistance (Cremonini et al, 2016). In this study, we investigated whether improved insulin sensitivity caused by EC supplementation could be in part caused by EC capacity to inhibit adipose tissue inflammation, ER and oxidative stresses.…”

“…EC supplementation inhibits inflammation, ER and oxidative stresses in visceral adipose tissue and exerts direct effects in adipocytes. This can in part explain the capacity of dietary EC and EC-rich foods to improve insulin sensitivity in rodents and humans (Shrime et al, 2011) (Grassi et al, 2008) (Davison et al, 2008) (Davison et al, 2008; Bettaieb et al, 2014; Cremonini et al, 2016). …”

Anti-Diabetic Effects of the Ethyl-Acetate Fraction of Trichilia catigua in Streptozo-tocin-Induced Type 1 Diabetic Rats

“…On the other hand, recent studies have shown antiinflammatory and antioxidant effects of PB2 and EPC, which exert positive effects by improving diabetes comorbidities. They were observed to bring improvement in insulin sensitivity and to exert a protective effect against diabetic nephropathy and cardiomyopathy [20,21].…”

Phenolic profiles and cellular antioxidant activity of longan pulp of 24 representative Chinese cultivars

“…Epicatechin is present in high concentrations in many plant foods, especially in fruits. Many healthy effects of epicatechin have been reported previously, including improving insulin sensitivity, [22] anti-allergy, [23] retarding Alzheimer's disease, [24] etc. Epicatechin was detected in all 15 determined Bulgarian fruits, [25] except melon.…”