P 196 - The intestinal/liver axis in the capacity of anthocyanidins to mitigate high fat diet-induced insulin resistance

Abstract

An increased permeability of the intestinal barrier is proposed as one underlying factor of obesity-associated pathologies. Consumption of high fat diet (HFD) is associated with intestinal permeabilization and increased paracellular transport of endotoxins, which can promote steatosis and insulin resistance. We investigated the capacity of dietary anthocyanidins (AC) to mitigate steatosis and improve insulin sensitivity in HFD-fed mice. Male C57BL/6 J mice were fed for 14 w control (C) or high fat (HF) diet, with or without supplementation with 2, 20, or 40 mg/kg BW of a blend of AC-rich plant extracts (ACE). The consumption of HFD caused overweight and insulin resistance, which were mitigated by ACE consumption. Concurrently, ACE prevented HFD-induced intestinal permeabilization, altered expression of ileum tight junction proteins (decreased ZO-1 and occludin) and endotoxemia. AC protection of barrier permeability is in part due to the inhibition of HFD-induced ileum ERK1/2 and AMPK activation, increased GLP-2 levels, and mitigation of dysbiosis. Consistently, the highest AC dose prevented steatosis and improved blood and liver inflammation and oxidative stress. Findings suggest that ACE supplementation could be an important strategy to mitigate obesity and Western style diets-associated insulin resistance in part through the preservation of intestinal barrier integrity.