Dietary Polyphenols to Combat Nonalcoholic Fatty Liver Disease via the Gut–Brain–Liver Axis: A Review of Possible Mechanisms

Wang, Zhenyu; Zeng, Maomao; Wang, Zhaojun; Qin, Fang; Chen, Jie; He, Zhiyong

doi:10.1021/acs.jafc.1c00751

Cited by 40 publications

(40 citation statements)

References 167 publications

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“…The presence or absence of intestinal germs capable of metabolizing polyphenols could, at least in part, explain the inter-individual variability of the beneficial effects on NAFLD observed as a result of polyphenol dietary supplementations. Because these agents, by changing the intestinal redox state, are, in turn, able to control the different subpopulations of the microbiota, it may well be believed that the microbiota-polyphenol interconnection may represent a new target for studies centered on diseases mediated by OS such as NAFLD [225,226].…”

Section: Modulation Of Gut-liver Axis: Effects On Oxidative Stressmentioning

confidence: 99%

Oxidative Stress in Non-Alcoholic Fatty Liver Disease

Smirne

Croce

Benedetto

et al. 2022

Livers

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Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it still remains an orphan of adequate therapies. This review highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive oxygen species generators, including those produced in the gastrointestinal tract, contribute to the lipotoxic hepatic (and extrahepatic) damage by fatty acids and a great variety of their biologically active metabolites in a “multiple parallel-hit model”. This leads to inflammation and fibrogenesis and contributes to NAFLD progression. The alterations of the oxidant/antioxidant balance affect also metabolism-related organelles, leading to lipid peroxidation, mitochondrial dysfunction, and endoplasmic reticulum stress. This OS-induced damage is at least partially counteracted by the physiological antioxidant response. Therefore, modulation of this defense system emerges as an interesting target to prevent NAFLD development and progression. For instance, probiotics, prebiotics, diet, and fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. The OS and its counter-regulation are under the influence of individual genetic and epigenetic factors as well. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors, coupled with new OS biomarkers, will likely assist in noninvasive diagnosis and monitoring of NAFLD progression and in further personalizing treatments.

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Section: Modulation Of Gut-liver Axis: Effects On Oxidative Stressmentioning

confidence: 99%

Oxidative Stress in Non-Alcoholic Fatty Liver Disease

Smirne

Croce

Benedetto

et al. 2022

Livers

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“…In addition, pathogenic bacteria from the intestinal microbiota can interactively regulate IL-17A production from immune or non-immune cells, which plays a major role in regulating gut mucosal immunity and pathogenesis of NAFLD, and thus accelerates the progression of NAFLD, a highly related complication of atherosclerosis ( 19 – 22 ). Moreover, pathogenic bacterial metabolites [i.e., lipopolysaccharides (LPS) and ethanol] from the lumen to the circulation rapidly relay information to the brain and damage the periphery, mainly in the liver and adipose tissues, by altering the central neurotransmitter systems ( 5 ). The vagus nerve in the gut can be directly activated by inflammatory signals to impair insulin sensitivity and hepatic steatosis associated with liver inflammation by altering the central neurotransmitter system ( 23 ).…”

Section: Pathogenesis Of Non-alcoholic Fatty Liver Disease Via the Gu...mentioning

confidence: 99%

“…NAFLD is a hepatic manifestation of metabolic syndrome and has become one of the most common causes of liver disease worldwide ( 3 ), accounting for a considerable burden on healthcare systems ( 4 ). Intracellular fat accumulation-induced steatosis and altered metabolic homeostasis are the primary features of NAFLD ( 5 ). A high prevalence of NAFLD (33.6%) was observed in patients with inflammatory bowel disease (IBD) ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

“…RSs are indigestible carbohydrates but fermentable for gut microbiota; thus, they are widely believed to be effective prebiotics that improve the production of short-chain fatty acids (SCFAs), which benefits the gut microbiome structure and overall human health ( 8 ). Current findings suggest that dietary supplementation with probiotics, functional oligosaccharides, and dietary fibers can help maintain gut bacterial balance and improve immune homeostasis in the gut, which is potentially beneficial for NAFLD amelioration ( 5 , 9 ). However, the role and underlying mechanism of RSs in ameliorating NAFLD by enhancing gut microenvironment homeostasis remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Amelioratory Effect of Resistant Starch on Non-alcoholic Fatty Liver Disease via the Gut-Liver Axis

et al. 2022

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Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome with a global prevalence. Impaired gut barrier function caused by an unhealthy diet plays a key role in disrupting the immune-metabolic homeostasis of the gut-liver axis (GLA), leading to NAFLD. Therefore, dietary interventions have been studied as feasible alternative therapeutic approaches to ameliorate NAFLD. Resistant starches (RSs) are prebiotics that reduce systemic inflammation in patients with metabolic syndrome. The present review aimed to elucidate the mechanisms of the GLA in alleviating NAFLD and provide insights into how dietary RSs counteract diet-induced inflammation in the GLA. Emerging evidence suggests that RS intake alters gut microbiota structure, enhances mucosal immune tolerance, and promotes the production of microbial metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids. These metabolites directly stimulate the growth of intestinal epithelial cells and elicit GPR41/GPR43, FXR, and TGR5 signaling cascades to sustain immune-metabolic homeostasis in the GLA. The literature also revealed the dietary-immune-metabolic interplay by which RSs exert their regulatory effect on the immune-metabolic crosstalk of the GLA and the related molecular basis, suggesting that dietary intervention with RSs may be a promising alternative therapeutic strategy against diet-induced dysfunction of the GLA and, ultimately, the risk of developing NAFLD.

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“…Polyphenols are micronutrients widely present in plants and the regulation of NAFLD by dietary polyphenol has been reviewed extensively. 13 Accordingly, 6-G, the main active polyphenol of ginger, has been reported to exert antioxidant, 14 anti-inflammatory, 15 anticancer, 16 neuroprotective, 17 anti-obesity, 18 and antihepatic steatosis 19 , 20 effects. However, the exact mechanism involved in the prevention of hepatic steatosis and the role of miRNAs in its regulation remain unknown.…”

mentioning

confidence: 99%

6-Gingerol Ameliorates Hepatic Steatosis via HNF4α/miR-467b-3p/GPAT1 Cascade

Ahn

Lee

Jung

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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BACKGROUND & AIMS:The development of nonalcoholic fatty liver disease (NAFLD) can be modulated by microRNAs (miRNA). Dietary polyphenols modulate the expression of miRNA such as miR-467b-3p in the liver. In addition, 6-gingerol (6-G), the functional polyphenol of ginger, has been reported to ameliorate hepatic steatosis; however, the exact mechanism involved and the role of miRNA remain elusive. In this study, we assessed the role of miR-467b-3p in the pathogenesis of hepatic steatosis and the regulation of miR-467b-3p by 6-G through the hepatocyte nuclear factor 4a (HNF4a).METHODS: miR-467b-3p expression was measured in free fatty acid (FFA)-treated hepatocytes or liver from high-fat diet (HFD)-fed mice. Gain-or loss-of-function of miR-467b-3p was induced using miR-467b-3p-specific miRNA mimic or miRNA inhibitor, respectively. 6-G was exposed to FFA-treated cells and HFD-fed mice. The HNF4a/miR-467b-3p/GPAT1 axis was measured in mouse and human fatty liver tissues. RESULTS:We found that miR-467b-3p was down-regulated in liver tissues from HFD-fed mice and in FFA-treated Hepa1-6 cells. Overexpression of miR-467b-3p decreased intracellular lipid accumulation in FFA-treated hepatocytes and mitigated hepatic steatosis in HFD-fed mice via negative regulation of glycerol-3-phosphate acyltransferase-1 (GPAT1). In addition, miR-467b-3p up-regulation by 6-G was observed. 6-G inhibited FFA-induced lipid accumulation and mitigated hepatic steatosis. Moreover, it increased the transcriptional activity of HNF4a, resulting in the increase of miR-467b-3p and subsequent decrease of GPAT1. HNF4a/miR-467b-3p/GPAT1 signaling also was observed in human samples with hepatic steatosis. CONCLUSIONS:Our findings establish a novel mechanism by which 6-G improves NAFLD. This suggests that targeting of the HNF4a/miR-467b-3p/GPAT1 cascade may be used as a potential therapeutic strategy to control NAFLD.

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Dietary Polyphenols to Combat Nonalcoholic Fatty Liver Disease via the Gut–Brain–Liver Axis: A Review of Possible Mechanisms

Cited by 40 publications

References 167 publications

Oxidative Stress in Non-Alcoholic Fatty Liver Disease

Oxidative Stress in Non-Alcoholic Fatty Liver Disease

Amelioratory Effect of Resistant Starch on Non-alcoholic Fatty Liver Disease via the Gut-Liver Axis

6-Gingerol Ameliorates Hepatic Steatosis via HNF4α/miR-467b-3p/GPAT1 Cascade

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