ArticleThe Journal of clinical investigation2016
ChREBP regulates fructose-induced glucose production independently of insulin signaling.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06671756 (The Metabolic Response to Fructose Ingestion), which is not on this map. Cited by 144 papers, 2 of them syntheses 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.
The Metabolic Response to Fructose Ingestion
Who cites it
144 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Dietary sugar consumption and health: umbrella review.BMJ (Clinical research ed.) · 2023Pooled it
- Pooled it
- NAFLD-related SNPs are linked to changes in liver fat, as measured by the CAP score, and serum lipids in response to a 3-week sugar-sweetened beverage intervention: a pilot study.Food & function · 2026Trial
- Dietary sugar restriction reduces hepatic de novo lipogenesis in adolescent boys with fatty liver disease.The Journal of clinical investigation · 2021Trial
- A randomized 3-way crossover study indicates that high-protein feeding induces de novo lipogenesis in healthy humans.JCI insight · 2019Trial
- Manganese availability determines insulin sensitivity by enhancing Akt activity.bioRxiv : the preprint server for biology · 2026Article
- Sugar Shockwaves: How the Fructose-Glucose-ChREBP Pathway Hijacks Liver Metabolism.Life (Basel, Switzerland) · 2026Review
- ChREBP Is Dispensable for Myofiber Type Switch but Promotes Skeletal Muscle Regeneration.Nutrients · 2026Article
- Fructose: metabolic signal and modern hazard.Nature metabolism · 2026Review
- Low-dose galactose rebalances HBP-mTORC1-SREBP-1c signaling to suppress hepatic lipogenesis and protect against early-stage alcohol-related liver disease.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- New Insight Into Male Infertility: Deviation From Basic Tenets of Life.Oxidative medicine and cellular longevity · 2026Review
- Fructose uptake by brown adipose tissue is independent of carbohydrate response element-binding protein and does not cause elevatedActa biochimica et biophysica Sinica · 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
- Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in citrin deficiency.Nature metabolism · 2025Article
- Glucose metabolic dysfunction surpasses dyslipidemia in driving hepatic steatosis and fibrosis: evidence from a nationally representative population.Diabetology & metabolic syndrome · 2025Article
- Hepatic Insulin Resistance and Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: New Insights into Mechanisms and Clinical Implications.Diabetes & metabolism journal · 2025Review
- Dietary fibre-adapted gut microbiome clears dietary fructose and reverses hepatic steatosis.Nature metabolism · 2025Article
- The induced-fit and catalytic mechanisms of human G6PC1.Cell discovery · 2025Article
- Food Nutrients and Bioactive Compounds for Managing Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comprehensive Review.Nutrients · 2025Review
- Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunctionassociated steatotic liver disease.Clinical and molecular hepatology · 2025Review
84 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
Obese, insulin-resistant states are characterized by a paradoxical pathogenic condition in which the liver appears to be selectively insulin resistant. Specifically, insulin fails to suppress glucose production, yet successfully stimulates de novo lipogenesis. The mechanisms underlying this dysregulation remain controversial. Here, we hypothesized that carbohydrate-responsive element-binding protein (ChREBP), a transcriptional activator of glycolytic and lipogenic genes, plays a central role in this paradox. Administration of fructose increased hepatic hexose-phosphate levels, activated ChREBP, and caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and hepatic steatosis in mice. Activation of ChREBP was required for the increased expression of glycolytic and lipogenic genes as well as glucose-6-phosphatase (G6pc) that was associated with the effects of fructose administration. We found that fructose-induced G6PC activity is a major determinant of hepatic glucose production and reduces hepatic glucose-6-phosphate levels to complete a homeostatic loop. Moreover, fructose activated ChREBP and induced G6pc in the absence of Foxo1a, indicating that carbohydrate-induced activation of ChREBP and G6PC dominates over the suppressive effects of insulin to enhance glucose production. This ChREBP/G6PC signaling axis is conserved in humans. Together, these findings support a carbohydrate-mediated, ChREBP-driven mechanism that contributes to hepatic insulin resistance.
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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.