ArticleHepatology (Baltimore, Md.)2017
Hepatic FXR/SHP axis modulates systemic glucose and fatty acid homeostasis in aged mice.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 103 citations in OpenAlex.
- Bile acids as a "new hormone" in aging-related liver disease.Life medicine · 2026Review
- The effect of artificial intelligence-driven, computed tomography-based assessment of body composition parameters on 28-day mortality of patients with severe fever with thrombocytopenia syndrome: a retrospective cohort study.BMC infectious diseases · 2026Observational
- Farnesoid x Receptor Deficiency Promotes Hepatocytic Injury in Cyp2c70-Deficient Mice With a Human-Like Bile Acid Composition.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Inhibition of the Primary Bile Acid Synthesis Pathways in SD Rats at Different Altitudes.Animals : an open access journal from MDPI · 2026Article
- Bile acid signaling, metabolism, and aging.Liver research (Beijing, China) · 2026Review
- Liver-specific Nr1h4 deletion in mice with human-like bile acid composition causes severe liver injury.Journal of lipid research · 2025Article
- Bile acid regulation of xenobiotic nuclear receptors on the expressions of orosomucoids in the liver.American journal of physiology. Endocrinology and metabolism · 2025Article
- Dietary bile acid supplementation improves the intestinal health and growth performance of piglets partially through the FXR/AQPs pathway.Porcine health management · 2025Article
- Association between lipid accumulation products and relative handgrip strength: a large population-based study.Scientific reports · 2025Article
- Alterations in intestinal bile acid transport provide a therapeutic target in patients with post-bariatric hypoglycaemia.Nature metabolism · 2025Article
- Gut Commensal Barnesiella Intestinihominis Ameliorates Hyperglycemia and Liver Metabolic Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Molecular Mechanism of Farnesoid X Receptor Alleviating Glucose Intolerance in Turbot (Cells · 2024Article
- Review
- Farnesoid X receptor: From Structure to Function and Its Pharmacology in Liver Fibrosis.Aging and disease · 2024Review
- Bile acid signaling in the regulation of whole body metabolic and immunological homeostasis.Science China. Life sciences · 2024Review
- Article
- Roles ofFrontiers in genetics · 2024Article
- Impact of gut microbiota and associated mechanisms on postprandial glucose levels in patients with diabetes.Journal of translational internal medicine · 2023Article
- The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases.Gastroenterology · 2023Review
- Improvement of obesity-induced fatty liver disease by intermittent hypoxia exposure in a murine model.Frontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The nuclear receptors farnesoid X receptor (FXR; NR1H4) and small heterodimer partner (SHP; NR0B2) play crucial roles in bile acid homeostasis. Global double knockout of FXR and SHP signaling (DKO) causes severe cholestasis and liver injury at early ages. Here, we report an unexpected beneficial impact on glucose and fatty acid metabolism in aged DKO mice, which show suppressed body weight gain and adiposity when maintained on normal chow. This phenotype was not observed in single Fxr or Shp knockouts. Liver-specific Fxr/Shp double knockout mice fully phenocopied the DKO mice, with lower hepatic triglyceride accumulation, improved glucose/insulin tolerance, and accelerated fatty acid use. In both DKO and liver-specific Fxr/Shp double knockout livers, these metabolic phenotypes were associated with altered expression of fatty acid metabolism and autophagy-machinery genes. Loss of the hepatic FXR/SHP axis reprogrammed white and brown adipose tissue gene expression to boost fatty acid usage.
conclusionCombined deletion of the hepatic FXR/SHP axis improves glucose/fatty acid homeostasis in aged mice, reversing the aging phenotype of body weight gain, increased adiposity, and glucose/insulin tolerance, suggesting a central role of this axis in whole-body energy homeostasis. (Hepatology 2017;66:498-509).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.