Supplementation with anthocyanins reverts established endotoxemia in high fat-fed mice through the regulation of colonic physiology by modulating redox signaling

FRAGA, CESAR G.; CREMONINI, ELEONORA; IGLESIAS, DARIO E.; OTEIZA, PATRICIA I.

Congreso; Society for Free Radical Research-International; 2021

Consumption of high fat diets (HFD) can impair intestinal barrier integrity, leading to endotoxemia and associated unhealthy conditions. We previously observed that 15-w consumption of a HFD together with an anthocyanin (cyanidin and delphinidin glycosides)-rich blend (ACB), prevented HFD-induced alterations in intestinal monolayer integrity, endotoxemia and dysbiosis in mice. The current study investigated the effects of a short-term ACB supplementation on HFD-induced alterations of colonic physiology and endotoxemia. Six-week old C57BL/6J male mice were fed control or HF diets for 4 w. Then, mice on each group were subdivided in two groups that either continued on control and HF diets, or were supplemented with 40 mg ACB/kg BW for the subsequent 4 w. Consumption of the HFD for 8 w caused endotoxemia evaluated as plasma lipopolysaccharides (LPS), increases in circulating LPS-binding protein levels and alterations in parameters of colonic function. These events were mitigated by 4-w supplementation with ACB. Thus, in the colon, consumption of the HFD caused: i) an increase in TLR4 expression; ii) a decrease in tight junction protein levels, i.e. occludin, ZO-1 and claudin-1; iii) an increased expression of NADPH oxidase NOX1 and iv) the inhibition of redox sensitive pathways, i.e. NF-κB and ERK1/2. HFD consumption affected parameters of goblet cell differentiation and function. ACB acted mitigating HFD-downregulation of markers (mRNA levels) of goblet cell differentiation (Klf4) and mucin production (Muc2). ACB also reverted HFD-induced reduction of Tff3 mRNA levels, a key mediator of the intestinal mucosa healing process. The latter effects could be in part explained by ACB?s capacity to downregulate the PI3K/Akt pathway. In fact, ACB decreased HFD-induced PI3K upregulation and downstream activation of Akt. Our findings show that select anthocyanidins, particularly cyanidin and delphinidin, could mitigate HFD-induced alterations in colon physiology and the associated endotoxemia in part through the modulation of redox signaling.