The gut–liver axis in hepatocarcinoma: a focus on the nuclear receptor FXR and the enterokine FGF19

Piglionica, Marilidia; Cariello, Marica; Moschetta, Antonio

doi:10.1016/j.coph.2018.08.005

Cited by 21 publications

(18 citation statements)

References 46 publications

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“…However, administration of trinitrobenzenesulfonic acid to FXR +/+ mice only resulted in mild chronic inflammation. 109 Recent findings have indicated that the increased FGF19 might have the potential to promote liver tumorigenesis. 104 FXR expression is reported to inversely correlated with colitis-associated neoplastic progression.…”

Section: Bile Acids-activated Receptorsmentioning

confidence: 99%

“…In the ileum, activation of FXR induces the production of the fibroblast growth factor 19 (FGF19), which can reach the liver through the portal system to inhibit bile acids synthesis. 109 Recent findings have indicated that the increased FGF19 might have the potential to promote liver tumorigenesis. In FGF19 transgenic mice, hepatocellular carcinoma can be found by 10 months of age.…”

Section: Bile Acids-activated Receptorsmentioning

confidence: 99%

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The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

Song

Khan

et al. 2019

Intl Journal of Cancer

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The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids–microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids–microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.

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Section: Bile Acids-activated Receptorsmentioning

confidence: 99%

Section: Bile Acids-activated Receptorsmentioning

confidence: 99%

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

Song

Khan

et al. 2019

Intl Journal of Cancer

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“…Under normal condition, synthesis of cholesterol is tightly regulated by sterol regulatory element binding protein 2 (SREBP2) and its down-stream cholesterol synthesis enzymes such as HMG-CoA reductase (HMGCR) [ 6 , 7 ]. Nearly 60% synthesized cholesterol is transported from liver to plasma and plays an important role in keeping membrane structure and synthesis of hormones, and nearly 40% cholesterol is converted to bile acid by cholesterol-7α-hydroxylase (CYP7A1) [ 8 ]. Under the state of NAFLD, excessive lipid accumulation leads to steatosis in liver, and causes the up-regulation of SREBP2 and HMGCR, which results in cholesterol over-production [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Regulation effects of total flavonoids in Morus alba L. on hepatic cholesterol disorders in orotic acid induced NAFLD rats

Chen

et al. 2020

BMC Complement Med Ther

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Background Mulberry leaves are the dried leaves of Morus alba L., flavonoids from mulberry leaves (MLF) has showed regulatory effect on abnormal lipid metabolism, but the regulatory mechanism of MLF on cholesterol metabolism is still missing. This study was designed to investigate the effect of MLF and its active metabolite quercetin on regulating cholesterol disorders. Methods The mechanism of MLF on alleviating liver injury and regulating cholesterol was examined in dyslipidemic SD rats. The regulatory mechanism of quercetin for cholesterol disorders have also been detected through lipid laden HepG2 cell model. Results Our results showed that MLF significantly inhibited lipid accumulation and alleviate hepatic injury in NAFLD rat model. The hepatic expression level of SREBP2, HMGCR and miR-33a were significantly down-regulated, while CYP7A1 was induced by MLF treatment. In vitro, Quercetin significantly decreased lipid accumulation in HepG2 cells. Mechanistically, quercetin could inhibit the mRNA and protein expression level of SREBP2 and HMGCR with or without LDL treatment. In addition, quercetin could also reduce the LXRβ while induced SR-BI mRNA expression. Conclusion Our findings indicate that MLF and quercetin could reduce the excessive cholesterol accumulation in vivo and in vitro. These cholesterol-regulating phenomenon might attribute to its effect on down-regulating the expression of lipid-related markers such as SREBP2 and HMGCR, which may exert a protective role in the NAFLD treatment.

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“…Further, it has been shown that gut microbiota contribute to FXR activation via bile acids [165]. Activation of FXR promotes the synthesis of fibroblast growth factor 19 (FGF19) [165], which enters the liver through the portal vein and reduces de novo bile acid synthesis by inhibiting CYP7A1 in hepatocytes [166]. Therefore, gut microbiota are involved in regulating bile acid synthesis in the liver.…”

Section: Involvement Of Bile Acids In the Microbiota-gut-liver Axismentioning

confidence: 99%

Role of Gut Microbiota in Neuroendocrine Regulation of Carbohydrate and Lipid Metabolism via the Microbiota-Gut-Brain-Liver Axis

2020

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Gut microbiota play an important role in maintaining intestinal health and are involved in the metabolism of carbohydrates, lipids, and amino acids. Recent studies have shown that the central nervous system (CNS) and enteric nervous system (ENS) can interact with gut microbiota to regulate nutrient metabolism. The vagal nerve system communicates between the CNS and ENS to control gastrointestinal tract functions and feeding behavior. Vagal afferent neurons also express receptors for gut peptides that are secreted from enteroendocrine cells (EECs), such as cholecystokinin (CCK), ghrelin, leptin, peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1), and 5-hydroxytryptamine (5-HT; serotonin). Gut microbiota can regulate levels of these gut peptides to influence the vagal afferent pathway and thus regulate intestinal metabolism via the microbiota-gut-brain axis. In addition, bile acids, short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and Immunoglobulin A (IgA) can also exert metabolic control through the microbiota-gut-liver axis. This review is mainly focused on the role of gut microbiota in neuroendocrine regulation of nutrient metabolism via the microbiota-gut-brain-liver axis.2 of 21 formate, acetate, propionate, and butyrate, which are related to maintaining intestinal epithelium and permeability [11]. Further, SCFAs regulate glucose and lipid metabolism as well as immune and inflammatory responses [12,13]. Hence, gut microbiota also plays an important role in immune systems, inflammation, and cancer prevention of the host [14,15]. The enteric nervous system (ENS) is reported to be involved in intestinal metabolic regulation, and enteric neurons and intestinal neurotransmitters play an important role in ENS regulation [16][17][18]. The gut contains full ENS reflex circuits, such as motor neurons, interneurons, and sensory neurons, and these neurons transfer information between the ENS and central nervous system (CNS). The vagal nerve pathway communicates between the CNS and ENS, which has remarkable impact on regulating gastrointestinal tract functions and feeding behavior [19,20]. Thus, the vagal nerve system is also involved in intestinal metabolic regulation through the gut-brain axis. Vagal afferent neurons express receptors for gut peptides, such as cholecystokinin (CCK), ghrelin, leptin, peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1), 5-hydroxytryptamine (5-HT) and so on, which are secreted from enteroendocrine cells (EECs) [20][21][22]. When vagal afferent neurons sense these types of gut peptides, the corresponding gut information will transfer to the CNS and exert various reactions. At the same time, gut microbiota can regulate these gut peptides, such as CCK, ghrelin, leptin, PYY, GLP-1, 5-HT levels to influence vagal afferent pathway, and then regulated intestinal metabolic metabolism via the microbiota-gut-brain axis [23][24][25].The importance of the gut-brain axis in human health and disease has been known for a long period. However, it has only been re...

show abstract

The gut–liver axis in hepatocarcinoma: a focus on the nuclear receptor FXR and the enterokine FGF19

Cited by 21 publications

References 46 publications

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

Regulation effects of total flavonoids in Morus alba L. on hepatic cholesterol disorders in orotic acid induced NAFLD rats

Role of Gut Microbiota in Neuroendocrine Regulation of Carbohydrate and Lipid Metabolism via the Microbiota-Gut-Brain-Liver Axis

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