Reversal of Increase in Intestinal Permeability by Mangifera indica Seed Kernel Extract in High-Fat Diet-Induced Obese Mice

Abstract

Obesity and hyper-intestinal permeability are interconnected. This study is designed to evaluate the ability of Mangifera indica seed kernel extract (MESK) in restoring the intestinal barrier and preventing obesity and associated metabolic complications in a high-fat diet-induced obese mouse model. Four groups of Swiss albino mice: (1) normal diet (ND), (2) high-fat diet (HFD), (3) HFD + Orlistat (100 µg/kg), and (4) HFD + MESK (75 µg/kg), were used to monitor various biochemical parameters associated with metabolic syndrome (glucose, total cholesterol, triglycerides) and body weight in an eight-week-long study. In vivo intestinal permeability was determined by the FITC-dextran method. Interestingly, MESK significantly reduced HFD-induced body weight gain, hepatic lipid accumulation, hepatic fibrosis, hyperglycemia, and dyslipidemia. Additionally, MESK treatment restored the expression of tight junction protein Zonula Occludens-1 (ZO-1) and Claudin-1 and hence prevented increased intestinal permeability induced by a high-fat diet. Moreover, it also increased the expression of potent satiety molecule Nesfatin-1 in the mouse jejunum. Our results, for the first time, establish MESK as a nutraceutical which prevents disruption of the intestinal barrier and thereby intercepts the adverse consequences of compromised intestinal permeability such as obesity, hyperglycemia, dyslipidemia, and systemic inflammation.

Leaky Gut: Effect of Dietary Fiber and Fats on Microbiome and Intestinal Barrier

“…HFD can induce an increase in intestinal permeability in mice or rats with decreased mRNA or protein expression of TJ including claudins-1, claudins-2, claudins-3, and ZO-1 [ 114 , 115 , 116 , 117 ]. More specifically, in IL-10 knockout mice with IBD, IBD-like colitis is spontaneously triggered with an increase in intestinal permeability [ 118 ].…”

The Anti‐Obesity and Anti‐Inflammatory Capabilities of Pterostilbene and its Colonic Metabolite Pinostilbene Protect against Tight Junction Disruption from Western Diet Feeding

“…These combined benefits may be crucial to tight junction protection (in terms of enhancing expression of ZO-1, claudin1, and occludin). Tight junction disruption has previously been observed in obesity, [32][33][34] diabetes, [35] and inflammation. [36] Among these factors, pro-inflammatory cytokines (TNF-𝛼, IL-1𝛽, and IFN-𝛾) were found to cause disturbance in intestinal tight junction barriers.…”

Intestinal Barrier and Permeability in Health, Obesity and NAFLD

“…C10 (caprate) [ 222 ] and not lauric acid [ 221 ] is responsible for the conformational alteration of TJ proteins and the mechanism involves occludin and ZO-1. In the rodent model, the high-fat diet (HFD) increases gut permeability and changes are associated with decreased mRNA or protein expression of TJ (claudins-1-3, ZO-1) [ 223 , 224 , 225 , 226 ]. More specifically, in IL-10 knockout mice with IBD, IBD-like colitis is spontaneously triggered with an increase in gut permeability [ 227 ].…”