Supplementation with cyanidin and delphinidin mitigates high fat diet-induced endotoxemia and associated liver inflammation in mice†
Consumption of high fat diets (HFD) and the associated metabolic endotoxemia can initiate liver inflammation and lipid deposition that with time can progress to non-alcoholic fatty liver disease (NAFLD). We previously observed that 14 weeks supplementation with the anthocyanidins cyanidin and delphinidin mitigated HFD-induced metabolic endotoxemia and liver insulin resistance, steatosis, inflammation and oxidative stress. This work investigated if a 4-week supplementation of mice with a cyanidin- and delphinidin-rich extract (CDRE) could mitigate or reverse HFD (60% calories from lard fat)-induced liver steatosis and inflammation. After a first 4-weeks period on the HFD, mice showed increased endotoxemia and activation of liver proinflammatory signaling cascades. Supplementation with CDRE between weeks 4 and 8 did not mitigate liver steatosis or the altered lipid and glucose plasma levels. However, CDRE supplementation reverted HFD-induced metabolic endotoxemia, in parallel with the mitigation of the overexpression of hepatic TLR2 and TLR4, and of the activation of: (i) NF-κB, (ii) AP-1 and upstream mitogen-activated kinases p38 and ERK1/2, and (iii) HIF-1. Thus, even a short-term consumption of cyanidin and delphinidin could help mitigate the adverse consequences, i.e. metabolic endotoxemia and associated liver inflammation, triggered by the regular consumption of diets rich in fat.