Cocoa and cocoa flavanol epicatechin improve hepatic lipid metabolism in in vivo and in vitro models. Role of PKCζ

Diabetes alters lipid metabolism that could lead to hepatic steatosis. The present study aimed to investigate the effect of a cocoa-enriched diet in type 2 diabetic Zucker diabetic fatty (ZDF) rats and that of cocoa-flavanol epicatechin (EC) in high-glucose-exposed HepG2 cells on hepatic lipid metabolism. Male ZDF cocoa-fed-rats had decreased body weight gain and improved circulating and hepatic lipid levels. Similarly, EC alleviated the altered lipid values induced in high-glucose-challenged HepG2 cells. The lipid-lowering effect was related to diminished fatty acid synthesis (sterol-regulatory-element-binding protein-1-c and fatty-acid synthase down-regulation), and increased fatty-acid oxidation (proliferator-activated-receptor α up-regulation). These effects depended on 5′-AMP-activated-protein-kinase (AMPK), protein kinase B (AKT) and protein kinase C (PKC)-ζ, which phosphorylated levels returned to control values upon cocoa or EC administration. Moreover, PKCζ played a role on AKT and AMPK regulation. These findings suggest that cocoa and EC protect hepatocytes in vivo and in vitro by improving lipid metabolism through multiple-signalling pathways.