(-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance

Abstract

Increased permeability of the intestinal barrier is proposed as an underlying factor for obesity-associated pathologies. Consumption of high fat diets (HFD) is associated with increased intestinal permeabilization and increased paracellular transport of endotoxins which can promote steatosis and insulin resistance. This study investigated whether dietary (-)-epicatechin (EC) supplementation can protect the intestinal barrier against HFD-induced permeabilization and endotoxemia, and mitigate liver damage and insulin resistance. Mechanisms leading to loss of integrity and function of the tight junction (TJ) were characterized. Consumption of a HFD for 15 weeks caused obesity, steatosis, and insulin resistance in male C57BL/6J mice. This was associated with increased intestinal permeability, decreased expression of ileal TJ proteins, and endotoxemia. Supplementation with EC (2–20 mg/kg body weight) mitigated all these adverse effects. EC acted modulating cell signals and the gut hormone GLP-2, which are central to the regulation of intestinal permeability. Thus, EC prevented HFD-induced ileum NOX1/NOX4 upregulation, protein oxidation, and the activation of the redox-sensitive NF-κB and ERK1/2 pathways. Supporting NADPH oxidase as a target of EC actions, in Caco-2 cells EC and apocynin inhibited tumor necrosis alpha (TNFα)-induced NOX1/NOX4 overexpression, protein oxidation and monolayer permeabilization. Together, our findings demonstrate protective effects of EC against HFD-induced increased intestinal permeability and endotoxemia. This can in part underlie EC capacity to prevent steatosis and insulin resistance occurring as a consequence of HFD consumption.

Can Medicinal Plants and Bioactive Compounds Combat Lipid Peroxidation Product 4-HNE-Induced Deleterious Effects?

“…More importantly, (−)-epicatechin and apocynin are found to suppress NOX1/NOX4 overexpression, 4-HNE adducts and monolayer permeabilization by regulating redox sensitive signals in TNFα-exposed Caco-2 cells, further demonstrating the protection against the high fat diet-induced increased intestinal permeability. These results are consistent with the prevention of steatosis and insulin resistance under the treatment of (−)-epicatechin and apocynin [106]. The edible amaranth plants from around the world have strong antioxidant activity [127].…”

“…NOX inhibitor apocynin, isolated from Picrorhiza kurroa, has been found to attenuate insulin resistance in skeletal muscle of mice with metabolic syndrome. Another phytochemical, (−)-epicatechin, found in green tea and cocoa, also down-regulates NOX1/NOX4, reduces 4-HNE adducts from ileum cells, and mitigates high fat diet-induced insulin resistance and steatosis in male C57BL/6J mice by preventing oxidative stress [106]. Cyanidin and delphinidin are the most common aglycon forms of anthocyanins and also have NOX inhibitory activity to attenuate high fat-induced steatosis and control the adverse effects by reducing 4-HNE-protein adducts in mice [107].…”

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

“…Caspase‐3 and caspase‐9 activities were determined using commercial kits (Beyotime Institute of Biotechnology). The levels of antioxidant factors, including glutathione peroxidase (GPX), superoxide dismutase (SOD) and glutathione (GSH), were measured with ELISA kits purchased from Beyotime Institute of Biotechnology …”

“…The levels of antioxidant factors, including glutathione peroxidase (GPX), superoxide dismutase (SOD) and glutathione (GSH), were measured with ELISA kits purchased from Beyotime Institute of Biotechnology. 39,40…”

The Regulation of Host Intestinal Microbiota by Polyphenols in the Development and Prevention of Chronic Kidney Disease

“…These results jointly indicate the protective effects of epicatechin against high-fat diet (HFD)-related increased intestinal permeability and endotoxemia, and against cancer. This also partly explains epicatechin's ability to prevent steatosis and insulin resistance in people who consume an HFD (31). Further studies are needed to investigate the molecular mechanisms of bioactive catechins (32).…”