Trial reportThe Journal of clinical investigation2012
The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans.
Trial report in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
239 citing papers in PubMed, 1 synthesis or guideline pooled it, 388 citations in OpenAlex.
- Lipid homeostasis in diabetic kidney disease.International journal of biological sciences · 2024Pooled it
- Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease.The Journal of clinical investigation · 2020Trial
- Changes of the Fatty Acid Profile in Erythrocyte Membranes of Patients following 6-Month Dietary Intervention Aimed at the Regression of Nonalcoholic Fatty Liver Disease (NAFLD).Canadian journal of gastroenterology & hepatology · 2018Trial
- Palmitoleic acid is elevated in fatty liver disease and reflects hepatic lipogenesis.The American journal of clinical nutrition · 2015Trial
- Non-pharmacological treatment of MASLD.Diabetologia · 2026Review
- Canonical and Non-Canonical Regulators of Lipid Metabolism in the Liver and the "Liver-Other Organs" Axes.International journal of molecular sciences · 2026Review
- Palmitic Acid-Induced Hepatotoxicity in Adult Zebrafish: Molecular Mechanisms and Advances in Intervention.Biology · 2026Review
- The Pathophysiological Interrelationship Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Cardiovascular Disease.Antioxidants (Basel, Switzerland) · 2026Review
- Carbohydrate responsive element binding protein promotes colorectal carcinogenesis via Wnt/β-catenin pathway.Oncogene · 2026Article
- Targeting mTOR with vistusertib attenuates metabolic steatohepatitis and prevents HCC development.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Experimental Models of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of a Choline-Deficient and Cholesterol-Enriched Diet in Rats.International journal of molecular sciences · 2026Article
- ChREBP-mediated regulation of lipid metabolism in liver and brown adipose tissue of long-lived mice.GeroScience · 2026Article
- Restoring Mitochondrial Homeostasis: Therapeutic Strategies for Metabolic Dysfunction-Associated Fatty Liver Disease.International journal of molecular sciences · 2026Review
- Plasma GLP-1 (Glucagon-like Peptide-1) Depletion Is Correlated with Dysregulation of Adipocytokine in Type 2 Diabetic Patients With or Without Metabolic-Associated Fatty Liver Disease (MAFLD): A Cross-Sectional Study Related to Gender-Sex Disparities.International journal of molecular sciences · 2026Article
- Hepatocyte Circadian Clocks Control Cholesterol Metabolism and Protect From Metabolic Dysfunction-Associated Steatohepatitis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Flavonoids in MASLD: preclinical mechanisms, pharmacological targets, and translational challenges.Frontiers in pharmacology · 2026Review
- Ectopic lipid deposition in kidney diseases: mechanisms in specific cell types and therapeutic strategies.Frontiers in endocrinology · 2026Review
- Review
- Role of ChREBP-PPARα-FGF21 Axis in Metabolic Dysfunction of MASLD.International journal of molecular sciences · 2025Article
- Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways.Clinical science (London, England : 1979) · 2025Review
179 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 10 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with all features of the metabolic syndrome. Although deposition of excess triglycerides within liver cells, a hallmark of NAFLD, is associated with a loss of insulin sensitivity, it is not clear which cellular abnormality arises first. We have explored this in mice overexpressing carbohydrate responsive element-binding protein (ChREBP). On a standard diet, mice overexpressing ChREBP remained insulin sensitive, despite increased expression of genes involved in lipogenesis/fatty acid esterification and resultant hepatic steatosis (simple fatty liver). Lipidomic analysis revealed that the steatosis was associated with increased accumulation of monounsaturated fatty acids (MUFAs). In primary cultures of mouse hepatocytes, ChREBP overexpression induced expression of stearoyl-CoA desaturase 1 (Scd1), the enzyme responsible for the conversion of saturated fatty acids (SFAs) into MUFAs. SFA impairment of insulin-responsive Akt phosphorylation was therefore rescued by the elevation of Scd1 levels upon ChREBP overexpression, whereas pharmacological or shRNA-mediated reduction of Scd1 activity decreased the beneficial effect of ChREBP on Akt phosphorylation. Importantly, ChREBP-overexpressing mice fed a high-fat diet showed normal insulin levels and improved insulin signaling and glucose tolerance compared with controls, despite having greater hepatic steatosis. Finally, ChREBP expression in liver biopsies from patients with nonalcoholic steatohepatitis was increased when steatosis was greater than 50% and decreased in the presence of severe insulin resistance. Together, these results demonstrate that increased ChREBP can dissociate hepatic steatosis from insulin resistance, with beneficial effects on both glucose and lipid metabolism.
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What OpenQuestion holds
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.