{
  "abstract": "Background Farnesoid X receptor (FXR) has been identified as a therapeutic target for metabolic dysfunction-associated steatohepatitis (MASH). Hepatic FXR is especially critical in suppressing liver inflammation. FXR agonism and antagonism have both proven to be beneficial in the mitigation of MASH, leading to much controversy in the field, particularly regarding FXR signalling in the gut. The objective of this study was to determine the effects of ursodeoxycholic acid (UDCA), a postulated gut FXR antagonist with liver protective effects, on the mitigation and prevention of MASH development in mice with hepatic FXR deficiency.Methods For this experiment, six-week-old to eight week-old male and female liver-specific FXR knockout (FXR hep-/-) and control (FXRhep flox/flox) mice were fed either a low-fat control diet (CTL) or a MASH ‘Fast Food’ diet (Western diet with 21% milk fat, 1.25% cholesterol and 34% sucrose) both supplemented with or without 0.1% (weight/weight; w/w) UDCA for 16 weeks.Results UDCA feeding tended to reduce alanine aminotransferase levels and decrease liver lipids in the male mice. Supplementation of UDCA showed a trend towards increased UDCA and tauroursodeoxycholic acid (TUDCA) levels in serum, liver and intestine, although the male mice displayed more than twice the amount of these bile acids compared with the female mice. CTL-UDCA feeding resulted in a significant induction of Fxr and Fgf15 mRNA expression in the ileum of the male mice.Conclusion The data strongly suggest that UDCA seems to act as an FXR agonist, especially in the ileum, which contrasts with previous reports that UDCA acts as a gut FXR antagonist. In addition, UDCA seems to be exerting liver protective effects predominantly in the male mice.",
  "authors": [
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Zakiyah R Henry"
    },
    {
      "affiliations": [
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Syeda Maliha"
    },
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Veronia Basaly"
    },
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Zhenning Yang"
    },
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Rulaiha E Taylor"
    },
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Katherine Otersen"
    },
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Vik Meadows"
    },
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Daniel Rizzolo"
    },
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Mary Stofan"
    },
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Anisha Bhattacharya"
    },
    {
      "affiliations": [
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Peihong Zhou"
    },
    {
      "affiliations": [
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Anita Brinker"
    },
    {
      "affiliations": [
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Ill Yang"
    },
    {
      "affiliations": [
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Lanjing Zhang"
    },
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Laurie B Joseph"
    },
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Brian Buckley"
    },
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA"
      ],
      "name": "Bo Kong"
    },
    {
      "affiliations": [
        "Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA",
        "Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA",
        "Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey, USA",
        "Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA",
        "Department of Veterans Affairs New Jersey Health Care System, East Orange, New Jersey, USA"
      ],
      "name": "Grace L Guo"
    }
  ],
  "title": "Ursodeoxycholic acid acts as an ileal FXR agonist in male mice with hepatic deficiency of FXR",
  "uid": "0def3c40-96b8-5fd7-b045-a263ef14c011"
}