(-)-Epicatechin inhibits ER Stress in adipocytes and in adipose tissue from high fat-fed obese mice

KANG H; OTEIZA PI; CREMONINI E; VAZQUEZ PRIETO MA; KANG J

Davis, California

Congreso; Oxidants and Antioxidants in Biology: Redox Medicine and Nutrition; 2016

Oxygen Club of California

Obesity and overweight are a major health concern worldwide. Obesity is associated with the development of insulin resistance and endoplasmic reticulum (ER) stress. Our previous studies showed that the flavan-3ol (-)-epicatechin (EC) mitigates obesity-induced insulin resistance in mice. Given the proposed role of ER stress in the development of insulin resistance as a consequence of overnutrition, this study investigated the hypothesis that EC and its metaboletes (ECM) can improve insulin sensitivity by preventing high fat-induced ER stress both in vivo and in vitro. In vivo: mice were fed for 15w: a contro diet (C), hich fat diets without (HF) or with supplementation of EC (20mgEC/Kg BW). In vitro: 3T3-L1 adipocytes were treated with .25mM Pal, and with or without EC(0.0-1uM) or ECM (1uM). The activation of the tree ER stress branch components (PERK, IRE1α, ATF6, XBP-1, JNK, eIF2α) was assessed by Western blot. In adipose tissue and in 3T3 cells EC mitigated/decreased high fat- and palmitate-induced activation of IREα, XBP-1 and JNK. While EC did not affect PERK activation both in adipocytes and HF adipose tissue, it inhibited eIF2α in adipocytes. Cleaved ATF-6 was increased by Pal and HF diet but was not affected by EC. In 3T3-L1 cells ECM had similar effects to those of EC. Overall results suggest that the inhibition of select ER stress branches (particularly IREα), can in part explain the capacity of dietary EC to mitigate insulin resistance occurring as a consequence of overnutrition.