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Nuclear receptor subfamily 1 group H member 4 (NR1H4)

Nuclear receptor subfamily 1 group H member 4, also known as farnesoid X receptor (FXR), is a ligand-activated nuclear receptor that functions as a key regulator of bile acid homeostasis and broader metabolic signaling.

Where the papers sit

13 papers from the last 6 months study Nuclear receptor subfamily 1 group H member 4 (NR1H4) directly · updated from PubMed 12 Oct 2026

Study type 0 clinical trials · 9 preclinical · 4 unclassified

Themes one subject · 1 paradigm shift · 1 new direction

Those 13 are all about one subject.

  • FXR in Fatty Liver Disease

    FXR and bile acid signaling are emerging as therapeutic targets for MASLD and MASH. Low-dose agonism, hepatic FXR mRNA delivery, microbiota remodeling and bile salt hydrolase activity are being used to restore metabolic and inflammatory balance. Benefits recur through SIRT1/NLRP3, NF-κB, cholesterol–bile acid metabolism and intestinal–hepatic signaling. The findings also show context dependence, as intestinal FXR loss can separate steatosis protection from inflammation and fibrosis.

    13 papers

PARADIGM SHIFT

Intestinal FXR inhibition can protect against metabolic steatosis or obesity even when FXR activation is treated as the therapeutic direction

Intestinal FXR-deficient mice with diet-induced MASH and Ligilactobacillus salivarius XA1416 or its UDCA metabolite in diet-induced obesity were expected, under the set’s prevailing FXR-activation model, to benefit from intestinal FXR stimulation; instead, intestinal FXR deficiency protected against obesity and hepatic steatosis, while also failing to protect against—and potentially uncoupling protection from—liver inflammation and fibrosis, and UDCA produced anti-obesity effects while acting as an intestinal FXR antagonist 42431962Jul 42092775May. This changes the therapeutic interpretation of FXR: intestinal antagonism may be advantageous for metabolic lipid outcomes, but those outcomes cannot be assumed to predict protection from progressive inflammatory or fibrotic liver disease.

NEW DIRECTION

FXR is presented as a regulator of tumor antigenicity and response to immunotherapy in MASH-associated hepatocellular carcinoma

MASH-related hepatocellular carcinoma with lipid-rich tumor cells was expected to involve FXR chiefly through bile-acid and metabolic regulation; instead, G-protein-coupled receptor 120-mediated FXR suppression reduced ABCB11-dependent bile-acid efflux, causing intracellular bile-acid retention that impaired NLRC5-mediated MHC-I antigen presentation and antitumor immunity, while the FXR agonist tropifexor restored immune control and synergized with immune-checkpoint blockade 42173274May. This extends NR1H4 beyond metabolic liver-disease treatment into tumor-cell antigenicity and immunotherapy response.

Papers

The 13 papers from the last 6 months that study Nuclear receptor subfamily 1 group H member 4 (NR1H4) directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.

By theme

FXR in Fatty Liver Disease (13)
  1. Hepatic delivery of FXR mRNA via lipid nanoparticles enhances the efficacy of a low-dose FXR agonist in the treatment of MASLD. Nanomedicine : nanotechnology, biology, and medicine · 3 Oct 2026 PMID 42829150
  2. Tetramethylpyrazine ameliorates metabolic dysfunction-associated steatohepatitis by modulating gut microbiota dysbiosis and restoring intestinal barrier integrity. British journal of pharmacology · 11 Sept 2026 PMID 42723361
  3. CD38 Inhibition Enhances FXR Signaling in Male Rats With Diabetic Steatohepatitis Through SIRT1-Dependent Suppression of NLRP3. FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 4 Aug 2026 PMID 42550583
  4. Babaodan Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease with Co-Modulation of FXR, NF-κB, and SLC22A7 in Bile Acid Metabolism. Journal of ethnopharmacology · 19 Jul 2026 PMID 42472598
  5. Intestinal FXR deficiency uncouples steatosis protection from liver inflammation and fibrosis in MASH-diet fed mice. Scientific reports · 10 Jul 2026 PMID 42431962
  6. The hawthorn (Crataegus pinnatifida) procyanidin extract attenuates nonalcoholic fatty liver disease in mice via remodeling the bile acid profile driven by gut microbiota and regulating the FXR pathway. Food & function · 16 Jun 2026 PMID 42300918
  7. Methyl dichloroasterrate alleviates lipopolysaccharide-induced neuroinflammation and depression-like behaviors in mice by upregulating FXR expression. International immunopharmacology · 12 Jun 2026 PMID 42284761
  8. Bile acid retention impairs tumoral antigen presentation and intrinsic tumor suppression in MASH-HCC. Cancer letters · 22 May 2026 PMID 42173274
  9. Differences in hepatic metabolism of Liandan Xiaoyan Formula between control and ulcerative colitis mice associated with FXR/PXR-CYP450 changes. Journal of pharmaceutical and biomedical analysis · 9 May 2026 PMID 42105596
  10. Discovery of Non-Carboxylic Steroidal FXR Agonist as a Promising Preclinical Candidate for Metabolic Dysfunction-Associated Steatohepatitis. Journal of medicinal chemistry · 8 May 2026 PMID 42102281
  11. A novel bile salt hydrolase-producing Ligilactobacillus salivarius prevents diet-induced obesity via regulation of bile acid metabolism and glucagon-like peptide 1 restoration. Gut microbes · 7 May 2026 PMID 42092775
  12. Dabupi decoction mitigates fluorouracil-induced intestinal mucositis via farnesoid X receptor activation and dihydropyrimidine dehydrogenase upregulation. Journal of ethnopharmacology · 2 May 2026 PMID 42069161
  13. Oroxin A in Linggui Zhugan Decoction in the treatment of MASH by regulating cholesterol-bile acid metabolism. Journal of ethnopharmacology · 30 Apr 2026 PMID 42061563

By study type

Preclinical: animal, cell and lab studies (9)
  1. CD38 Inhibition Enhances FXR Signaling in Male Rats With Diabetic Steatohepatitis Through SIRT1-Dependent Suppression of NLRP3. FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 4 Aug 2026 PMID 42550583
  2. The hawthorn (Crataegus pinnatifida) procyanidin extract attenuates nonalcoholic fatty liver disease in mice via remodeling the bile acid profile driven by gut microbiota and regulating the FXR pathway. Food & function · 16 Jun 2026 PMID 42300918
  3. Methyl dichloroasterrate alleviates lipopolysaccharide-induced neuroinflammation and depression-like behaviors in mice by upregulating FXR expression. International immunopharmacology · 12 Jun 2026 PMID 42284761
  4. Bile acid retention impairs tumoral antigen presentation and intrinsic tumor suppression in MASH-HCC. Cancer letters · 22 May 2026 PMID 42173274
  5. Differences in hepatic metabolism of Liandan Xiaoyan Formula between control and ulcerative colitis mice associated with FXR/PXR-CYP450 changes. Journal of pharmaceutical and biomedical analysis · 9 May 2026 PMID 42105596
  6. Discovery of Non-Carboxylic Steroidal FXR Agonist as a Promising Preclinical Candidate for Metabolic Dysfunction-Associated Steatohepatitis. Journal of medicinal chemistry · 8 May 2026 PMID 42102281
  7. A novel bile salt hydrolase-producing Ligilactobacillus salivarius prevents diet-induced obesity via regulation of bile acid metabolism and glucagon-like peptide 1 restoration. Gut microbes · 7 May 2026 PMID 42092775
  8. Dabupi decoction mitigates fluorouracil-induced intestinal mucositis via farnesoid X receptor activation and dihydropyrimidine dehydrogenase upregulation. Journal of ethnopharmacology · 2 May 2026 PMID 42069161
  9. Oroxin A in Linggui Zhugan Decoction in the treatment of MASH by regulating cholesterol-bile acid metabolism. Journal of ethnopharmacology · 30 Apr 2026 PMID 42061563
Unclassified: not yet indexed with MeSH (4)
  1. Hepatic delivery of FXR mRNA via lipid nanoparticles enhances the efficacy of a low-dose FXR agonist in the treatment of MASLD. Nanomedicine : nanotechnology, biology, and medicine · 3 Oct 2026 PMID 42829150
  2. Tetramethylpyrazine ameliorates metabolic dysfunction-associated steatohepatitis by modulating gut microbiota dysbiosis and restoring intestinal barrier integrity. British journal of pharmacology · 11 Sept 2026 PMID 42723361
  3. Babaodan Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease with Co-Modulation of FXR, NF-κB, and SLC22A7 in Bile Acid Metabolism. Journal of ethnopharmacology · 19 Jul 2026 PMID 42472598
  4. Intestinal FXR deficiency uncouples steatosis protection from liver inflammation and fibrosis in MASH-diet fed mice. Scientific reports · 10 Jul 2026 PMID 42431962
bioLLM/wiki is a literature-navigation aid for people who read primary research. It is not a medical resource, and it is not a substitute for a clinician, a pharmacist or the source papers themselves. Because the articles are drafted by language models, they can be incomplete or wrong in ways that read fluently. Please see the editorial policy and medical disclaimer before relying on anything here.

Written from 13 PubMed abstracts, each one listed by PMID above. Published: 2026-07-19. Last written: 2026-09-13 by GPT. Drafted by language models from published abstracts; not medical advice.