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Resveratrol attenuates high-fat diet-induced non-alcoholic steatohepatitis by maintaining gut barrier integrity and inhibiting gut inflammation through regulation of the endocannabinoid system.

Abstract

BACKGROUND & AIMS

This study aims to investigate the ameliorative effects of resveratrol (RSV) in a high-fat diet (HFD)-induced non-alcoholic steatohepatitis (NASH) rat model, focusing on the gut endocannabinoid system (ECS), regulated by RSV, in the maintenance of gut barrier integrity and inhibition of gut inflammation.

METHODS AND RESULTS

Male Sprague-Dawley (SD) rats were fed HFD with or without RSV for 6 weeks. The HFD caused increase in body weight, liver index, hepatic lipid accumulation, and inflammation, which was inhibited by RSV. RSV also attenuated gut microbial dysbiosis, with an increase in Akkermansia muciniphila, Ruminococcaceae, and Lachnospiraceae, and a decrease in Desulfovibrio. Moreover, RSV led to a reduction of metabolic endotoxemia and colon inflammation in HFD-fed rats. This was indicated by a decrease in bacterial invasion and translocation along with up-regulation of the mRNA levels of occludin, ZO1, claudin1, and down-regulation of FAK, MyD88, and IRAK4 in the distal colon. Furthermore, RSV inhibited HFD-induced elevation in the expression of cannabinoid receptor type 1 (CB1) mRNA and suppressed CB2 mRNA levels in the colon. The RSV-induced benefits regarding enhanced gut barrier integrity and reduced intestinal permeability were abrogated with a CB1 agonist, ACEA, whereas the inhibitory effect of RSV on the intestinal inflammation was abolished by a CB2 antagonist, AM630. Moreover, microbiota depletion using a cocktail of antibiotics was sufficient to block RSV-induced reduction in intestinal permeability and gut inflammation, as well as the altered mRNA expressions of CB1 and CB2 in the distal colon.

CONCLUSIONS

These data indicate that the ECS, particularly the expressions of CB1 and CB2, appears to play a crucial role in the RSV induced anti-NASH effect by maintaining the gut barrier integrity and inhibiting gut inflammation.

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  • Authors+Show Affiliations

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    Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, 400038, PR China.

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    Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, 400038, PR China.

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    Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, 400038, PR China.

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    Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, 400038, PR China.

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    Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, 400038, PR China.

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    Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, 400038, PR China.

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    Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, 400038, PR China.

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    Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, 400038, PR China. Electronic address: longgyin8341@hotmail.com.

    Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, 400038, PR China. Electronic address: mi_mt2009@hotmail.com.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31189495

    Citation

    Chen, Mengting, et al. "Resveratrol Attenuates High-fat Diet-induced Non-alcoholic Steatohepatitis By Maintaining Gut Barrier Integrity and Inhibiting Gut Inflammation Through Regulation of the Endocannabinoid System." Clinical Nutrition (Edinburgh, Scotland), 2019.
    Chen M, Hou P, Zhou M, et al. Resveratrol attenuates high-fat diet-induced non-alcoholic steatohepatitis by maintaining gut barrier integrity and inhibiting gut inflammation through regulation of the endocannabinoid system. Clin Nutr. 2019.
    Chen, M., Hou, P., Zhou, M., Ren, Q., Wang, X., Huang, L., ... Mi, M. (2019). Resveratrol attenuates high-fat diet-induced non-alcoholic steatohepatitis by maintaining gut barrier integrity and inhibiting gut inflammation through regulation of the endocannabinoid system. Clinical Nutrition (Edinburgh, Scotland), doi:10.1016/j.clnu.2019.05.020.
    Chen M, et al. Resveratrol Attenuates High-fat Diet-induced Non-alcoholic Steatohepatitis By Maintaining Gut Barrier Integrity and Inhibiting Gut Inflammation Through Regulation of the Endocannabinoid System. Clin Nutr. 2019 May 30; PubMed PMID: 31189495.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Resveratrol attenuates high-fat diet-induced non-alcoholic steatohepatitis by maintaining gut barrier integrity and inhibiting gut inflammation through regulation of the endocannabinoid system. AU - Chen,Mengting, AU - Hou,Pengfei, AU - Zhou,Min, AU - Ren,Qingbo, AU - Wang,Xiaolan, AU - Huang,Li, AU - Hui,Suocheng, AU - Yi,Long, AU - Mi,Mantian, Y1 - 2019/05/30/ PY - 2019/02/03/received PY - 2019/04/27/revised PY - 2019/05/21/accepted PY - 2019/6/14/entrez PY - 2019/6/14/pubmed PY - 2019/6/14/medline KW - Endocannabinoid receptor KW - Gut microbiota KW - Intestinal barrier KW - Non-alcoholic steatohepatitis KW - Resveratrol JF - Clinical nutrition (Edinburgh, Scotland) JO - Clin Nutr N2 - BACKGROUND & AIMS: This study aims to investigate the ameliorative effects of resveratrol (RSV) in a high-fat diet (HFD)-induced non-alcoholic steatohepatitis (NASH) rat model, focusing on the gut endocannabinoid system (ECS), regulated by RSV, in the maintenance of gut barrier integrity and inhibition of gut inflammation. METHODS AND RESULTS: Male Sprague-Dawley (SD) rats were fed HFD with or without RSV for 6 weeks. The HFD caused increase in body weight, liver index, hepatic lipid accumulation, and inflammation, which was inhibited by RSV. RSV also attenuated gut microbial dysbiosis, with an increase in Akkermansia muciniphila, Ruminococcaceae, and Lachnospiraceae, and a decrease in Desulfovibrio. Moreover, RSV led to a reduction of metabolic endotoxemia and colon inflammation in HFD-fed rats. This was indicated by a decrease in bacterial invasion and translocation along with up-regulation of the mRNA levels of occludin, ZO1, claudin1, and down-regulation of FAK, MyD88, and IRAK4 in the distal colon. Furthermore, RSV inhibited HFD-induced elevation in the expression of cannabinoid receptor type 1 (CB1) mRNA and suppressed CB2 mRNA levels in the colon. The RSV-induced benefits regarding enhanced gut barrier integrity and reduced intestinal permeability were abrogated with a CB1 agonist, ACEA, whereas the inhibitory effect of RSV on the intestinal inflammation was abolished by a CB2 antagonist, AM630. Moreover, microbiota depletion using a cocktail of antibiotics was sufficient to block RSV-induced reduction in intestinal permeability and gut inflammation, as well as the altered mRNA expressions of CB1 and CB2 in the distal colon. CONCLUSIONS: These data indicate that the ECS, particularly the expressions of CB1 and CB2, appears to play a crucial role in the RSV induced anti-NASH effect by maintaining the gut barrier integrity and inhibiting gut inflammation. SN - 1532-1983 UR - https://www.unboundmedicine.com/medline/citation/31189495/Resveratrol_attenuates_high-fat_diet-induced_non-alcoholic_steatohepatitis_by_maintaining_gut_barrier_integrity_and_inhibiting_gut_inflammation_through_regulation_of_the_endocannabinoid_system L2 - https://linkinghub.elsevier.com/retrieve/pii/S0261-5614(19)30231-6 DB - PRIME DP - Unbound Medicine ER -