ArticleCell metabolism2012
Impaired generation of 12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia.
Article in Cell metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
90 citing papers in PubMed, 149 citations in OpenAlex.
- Trial
- Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial.Scientific reports · 2016Trial
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation.Science advances · 2026Article
- Manganese availability determines insulin sensitivity by enhancing Akt activity.bioRxiv : the preprint server for biology · 2026Article
- Bile acids and bile acid modification in health and disease: from novel modifications to therapeutic interventions.Frontiers in endocrinology · 2026Review
- Bile acid signaling: from dynamic pool composition to inter-organ communication.Frontiers in endocrinology · 2026Review
- Genetic and dietary determinants of gut microbiome-bile acid interactions in the BXD genetic reference population.Nature communications · 2025Article
- The Framingham steatosis index as a predictor of advanced CKM syndrome in US adults: Evidence from NHANES 2001 to 2018.Medicine · 2025Article
- Differential roles of individual bile acid in physiology and disease.Pharmacological research · 2025Review
- Single-cell transcriptome analyses reveal the mechanism of mitochondrial activity in erectile dysfunction.Sexual medicine · 2025Article
- New drug therapies for metabolic dysfunction-associated steatohepatitis.Liver research (Beijing, China) · 2025Review
- Aerobic Capacity and Exercise Mediate Protection Against Hepatic Steatosis via Enhanced Bile Acid Metabolism.Function (Oxford, England) · 2025Article
- Bile acid metabolism in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- Clinical Features and Plasma Metabolites Analysis in Obese Chinese Children With Nonalcoholic Fatty Liver Disease.Journal of the Endocrine Society · 2025Article
- Comparative Analysis of γ-Cyclodextrin, Perilla Oil, and Their Inclusion Complexes on Liver Injury and Dyslipidemia Associated with Elevated Gastrointestinal 12-Hydroxylated Bile Acid Levels.Molecules (Basel, Switzerland) · 2025Article
- Article
- Silicon-Enriched Meat Ameliorates Diabetic Dyslipidemia by Improving Cholesterol, Bile Acid Metabolism and Ileal Barrier Integrity in Rats with Late-Stage Type 2 Diabetes.International journal of molecular sciences · 2024Article
- Comprehensive Clinical and Genetic Analyses of Circulating Bile Acids and Their Associations With Diabetes and Its Indices.Diabetes · 2024Article
- HSDL2 links nutritional cues to bile acid and cholesterol homeostasis.Science advances · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The association of type 2 diabetes with elevated plasma triglyceride (TG) and very low-density lipoproteins (VLDL), and intrahepatic lipid accumulation represents a pathophysiological enigma and an unmet therapeutic challenge. Here, we uncover a link between insulin action through FoxO1, bile acid (BA) composition, and altered lipid homeostasis that brings new insight to this longstanding conundrum. FoxO1 ablation brings about two signature lipid abnormalities of diabetes and the metabolic syndrome, elevated liver and plasma TG. These changes are associated with deficiency of 12α-hydroxylated BAs and their synthetic enzyme, Cyp8b1, that hinders the TG-lowering effects of the BA receptor, Fxr. Accordingly, pharmacological activation of Fxr with GW4064 overcomes the BA imbalance, restoring hepatic and plasma TG levels of FoxO1-deficient mice to normal levels. We propose that generation of 12α-hydroxylated products of BA metabolism represents a signaling mechanism linking hepatic lipid abnormalities with type 2 diabetes, and a treatment target for this condition.
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Registered trials
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.