Abstract
We evaluated the effectiveness of pharmacological doses of grape-seed proanthocyanidin extract (GSPE) in reversing intestinal barrier alterations and local inflammation in female Wistar rats fed a long-term obesogenic diet. Animals were fed a 17-week cafeteria diet (CAF diet), supplemented with daily GSPE doses (100 or 500 mg kg−1 body weight) during the final two weeks. CAF diet enhanced the intestinal permeation of an orally administered marker (ovalbumin, OVA) and increased the plasma levels of tumor necrosis factor-α (TNF-α) and lipopolysaccharides (LPS) in 2–3-fold. Ex vivo Ussing chamber assays showed a 55–70% reduction in transepithelial electrical resistance (TEER) and increased the TNF-α secretions in both small and large intestinal sections with a 25-fold increment in the ileum. Ileal tissues also presented a 4-fold increase of myeloperoxidase (MPO) activity. Both GSPE-treatments were able to restitute TEER values in the ileum and colon and to reduce plasma LPS to basal levels without a dose-dependent effect. However, effects on the OVA permeation and TNF-α secretion were dose and section-specific. GSPE also reduced ileal MPO activity and upregulated claudin 1 gene expression. This study provides evidence of the efficacy of GSPE-supplementation ameliorating diet-induced intestinal dysfunction and metabolic endotoxemia when administered at the end of a long-term obesogenic diet.
Highlights
It has been reported that there is a causal relationship between pathophysiological changes in the intestinal epithelium and obesity in animal models and humans [1,2,3]
We focused on intestinal permeability, local inflammatory status, metabolic endotoxemia and systemic inflammation
grape-seed proanthocyanidin extract (GSPE)-supplementation did not bring about any change in the final body weight or adiposity index compared to the CAF group, even though the body weight gain of the
Summary
It has been reported that there is a causal relationship between pathophysiological changes in the intestinal epithelium and obesity in animal models and humans [1,2,3]. High-saturated fat/high refined-carbohydrate diets, that are low in fiber and plant flavonoids, induce weight gain in humans and laboratory animals, and alterations in gut microbiota (dysbiosis) [7,8,9]. Intestinal dysfunction (increased permeability and local inflammation) [10]. Nutrients 2019, 11, 979 layers [11,12,13] This causes a local inflammatory response in the intestine that aggravates barrier function deficiency in a vicious cycle. When LPS reaches the general circulation due to the inability of the intestinal immune response to neutralize it, it can spread systemically causing metabolic endotoxemia and obesity-related complications such as adipose tissue dysfunction as well as systemic low-grade inflammation [14]
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