Anthocyanins protect the gastrointestinal tract from high fat diet-induced alterations in redox signaling, barrier integrity and dysbiosis

CREMONINI, ELEONORA; DAVERI, ELENA; MASTALOUDIS, ANGELA; ADAMO, ANA M.; MILLS, DAVID; KALANETRA, KAREN; HESTER, SHELLY N.; WOOD, STEVE M.; FRAGA, CESAR G.; OTEIZA, PATRICIA I.

Redox Biology

Elsevier

Año: 2019 vol. 26

2213-2317

The gastrointestinal (GI) tract can play a critical role in the development of pathologies associated with overeating,overweight and obesity. We previously observed that supplementation with anthocyanins (AC) (particularlyglycosides of cyanidin and delphinidin) mitigated high fat diet (HFD)-induced development of obesity,dyslipidemia, insulin resistance and steatosis in C57BL/6J mice. This paper investigated whether these beneficialeffects could be related to AC capacity to sustain intestinal monolayer integrity, prevent endotoxemia, and HFDassociateddysbiosis. The involvement of redox-related mechanisms were further investigated in Caco-2 cellmonolayers. Consumption of a HFD for 14 weeks caused intestinal permeabilization and endotoxemia, whichwere associated with a decreased ileum expression of tight junction (TJ) proteins (occludin, ZO-1 and claudin-1),increased expression of NADPH oxidase (NOX1 and NOX4) and NOS2 and oxidative stress, and activation ofredox sensitive signals (NF-κB and ERK1/2) that regulate TJ dynamics. AC supplementation mitigated all theseevents and increased GLP-2 levels, the intestinal hormone that upregulates TJ protein expression. AC alsoprevented, in vitro, tumor necrosis factor alpha-induced Caco-2 monolayer permeabilization, NOX1/4 upregulation,oxidative stress, and NF-κB and ERK activation. HFD-induced obesity in mice caused dysbiosis and affectedthe levels and secretion of MUC2, a mucin that participates in intestinal cell barrier protection and immuneresponse. AC supplementation restored microbiota composition and MUC2 levels and distribution in HFDfedmice. Thus, AC, particularly delphinidin and cyanidin, can preserve GI physiology in HFD-induced obesity inpart through redox-regulated mechanisms. This can in part explain AC capacity to mitigate pathologies, i.e.insulin resistance and steatosis, associated with HFD-associated obesity.