FXR in liver physiology: Multiple faces to regulate liver metabolism

Panzitt, Katrin; Wagner, Martin

doi:10.1016/j.bbadis.2021.166133

Cited by 87 publications

(65 citation statements)

References 214 publications

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“…BAs have long been known as detergents to facilitate lipid and nutrient absorption in the intestine. Since the identification in 1999 of the nuclear hormone receptor (NHR), FXR, as a BA-activated receptor, BAs have been extensively studied as critical signaling molecules regulating lipid, glucose, and energy metabolism [ 32 , 48 , 49 , 50 , 51 ]. The identification of BA-activated GPCRs, TGR5, and S1PR2 further expanded the role of BAs in regulating metabolic pathways [ 18 , 52 , 53 , 54 ].…”

Section: Bas As Signaling Moleculesmentioning

confidence: 99%

“…BAs differ in their potency in activating FXR. CDCA is the highest, followed by DCA, LCA, and CA [ 48 ]. In mice, CDCA and UDCA are converted to α-MCA and β-MCA by Cyp2c70, respectively [ 35 ].…”

Section: Bas As Signaling Moleculesmentioning

confidence: 99%

“…It has been identified that taurine-conjugated α-MCA and β-MCA are natural FXR antagonists [ 58 ]. The role of FXR in hepatic metabolism has been reviewed recently [ 48 , 55 , 59 ].…”

Section: Bas As Signaling Moleculesmentioning

confidence: 99%

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Bile Acid Receptors and the Gut–Liver Axis in Nonalcoholic Fatty Liver Disease

Xue

Lai

et al. 2021

Cells

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The prevalence of nonalcoholic fatty liver disease (NAFLD) has been significantly increased due to the global epidemic of obesity. The disease progression from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is closely linked to inflammation, insulin resistance, and dysbiosis. Although extensive efforts have been aimed at elucidating the pathological mechanisms of NAFLD disease progression, current understanding remains incomplete, and no effective therapy is available. Bile acids (BAs) are not only important physiological detergents for the absorption of lipid-soluble nutrients in the intestine but also metabolic regulators. During the last two decades, BAs have been identified as important signaling molecules involved in lipid, glucose, and energy metabolism. Dysregulation of BA homeostasis has been associated with NAFLD disease severity. Identification of nuclear receptors and G-protein-coupled receptors activated by different BAs not only significantly expanded the current understanding of NAFLD/NASH disease progression but also provided the opportunity to develop potential therapeutics for NAFLD/NASH. In this review, we will summarize the recent studies with a focus on BA-mediated signaling pathways in NAFLD/NASH. Furthermore, the therapeutic implications of targeting BA-mediated signaling pathways for NAFLD will also be discussed.

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Section: Bas As Signaling Moleculesmentioning

confidence: 99%

Section: Bas As Signaling Moleculesmentioning

confidence: 99%

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Bile Acid Receptors and the Gut–Liver Axis in Nonalcoholic Fatty Liver Disease

Xue

Lai

et al. 2021

Cells

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“…Fourth, we observed the relationship between effects of UDCA and FXR pathway in HS. A large number of literatures have shown that FXR, as a receptor for bile acids, plays an important role in reducing liver injury and promoting liver repair (23)(24)(25). Our study demonstrated that in the case of FXR (-/-), the in uence of UDCA was inhibited.…”

Section: Discussionmentioning

confidence: 50%

Ursodeoxycholic Acid (UDCA) Increases Lactate Clearance and Reduces Liver Injury by Inhibiting Farnesoid X Receptor (FXR) in Hemorrhagic Shock (HS)

Wang

Rui

et al. 2021

Preprint

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Background: Hemorrhagic shock (HS) is one of the leading causes of death worldwide. Acute liver injury (ALI) is an important manifestation of HS. Farnesoid X receptor (FXR) plays an important role in the liver protection of bile acids. Therefore, we designed this experiment to study the effect of ursodeoxycholic acid (UDCA) on acute liver injury and its relationship with the FXR pathway in HS.Methods: In this study, eighteen adult male C57BL/6 mice were randomly divided into 3 groups of six mice per group applying a table of random numbers: sham group; HS group and HS + UDCA group. Six FXR (-/-) adult male C57BL mice were classified as FXR (-/-) + HS + UDCA group. As to model of HS, MAP of 40 ± 5 mmHg was maintained for 1 hour. As to UDCA intervention, UDCA (300mg/kg) was given nasally fed. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) were quantified with chromatographic quantitative kits according to the manufacturer’s instructions. Lactate concentration was determined by an automatic biochemical analyzer. The liver tissues were stained with hematoxylin and eosin (H&E) and scored histopathologically.Results: Plasma ALT, AST and lactate levels decreased significantly after treatment with UDCA under HS conditions. Pathological scores of liver tissues decreased significantly after treatment with UDCA under HS conditions. In the case of FXR (-/-), the influence of UDCA was inhibited.Conclusions: UDCA can reduce ALT, AST and lactate levels and alleviate liver injury during HS through the FXR pathway.

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“…Their target genes have key roles in both embryonic development and adult homeostasis, and they are collectively implicated in a vast majority, if not all, of the biological processes of the body [ 11 , 17 ]. The hepatic roles of several of these receptors have been reviewed recently and, therefore, will not be discussed herein [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Roles of Estrogens in the Healthy and Diseased Oviparous Vertebrate Liver

et al. 2021

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The liver is a vital organ that sustains multiple functions beneficial for the whole organism. It is sexually dimorphic, presenting sex-biased gene expression with implications for the phenotypic differences between males and females. Estrogens are involved in this sex dimorphism and their actions in the liver of several reptiles, fishes, amphibians, and birds are discussed. The liver participates in reproduction by producing vitellogenins (yolk proteins) and eggshell proteins under the control of estrogens that act via two types of receptors active either mainly in the cell nucleus (ESR) or the cell membrane (GPER1). Estrogens also control hepatic lipid and lipoprotein metabolisms, with a triglyceride carrier role for VLDL from the liver to the ovaries during oogenesis. Moreover, the activation of the vitellogenin genes is used as a robust biomarker for exposure to xenoestrogens. In the context of liver diseases, high plasma estrogen levels are observed in fatty liver hemorrhagic syndrome (FLHS) in chicken implicating estrogens in the disease progression. Fishes are also used to investigate liver diseases, including models generated by mutation and transgenesis. In conclusion, studies on the roles of estrogens in the non-mammalian oviparous vertebrate liver have contributed enormously to unveil hormone-dependent physiological and physiopathological processes.

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FXR in liver physiology: Multiple faces to regulate liver metabolism

Cited by 87 publications

References 214 publications

Bile Acid Receptors and the Gut–Liver Axis in Nonalcoholic Fatty Liver Disease

Bile Acid Receptors and the Gut–Liver Axis in Nonalcoholic Fatty Liver Disease

Ursodeoxycholic Acid (UDCA) Increases Lactate Clearance and Reduces Liver Injury by Inhibiting Farnesoid X Receptor (FXR) in Hemorrhagic Shock (HS)

Roles of Estrogens in the Healthy and Diseased Oviparous Vertebrate Liver

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