Observational studyJCI insight2019
Impaired ketogenesis and increased acetyl-CoA oxidation promote hyperglycemia in human fatty liver.
Observational study in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
119 citing papers in PubMed, 191 citations in OpenAlex.
- Beneficial Effects of Carbohydrate Restriction in Type 2 Diabetes Can Be Traced to Changes in Hepatic Metabolism.The Journal of clinical endocrinology and metabolism · 2025Trial
- Effect of alternate day fasting combined with aerobic exercise on non-alcoholic fatty liver disease: A randomized controlled trial.Cell metabolism · 2023Trial
- Trial
- Sparing Muscle While Losing Fat: A Narrative Review of Ketogenic Diets and Lean Mass Preservation During Weight Loss.Nutrients · 2026Review
- Sequential Fractionation ofFoods (Basel, Switzerland) · 2026Article
- HFpEF and MASLD: converging mechanisms and clinical implications.Nature reviews. Cardiology · 2026Review
- Gut Mycobiota-Associated Tryptophan Catabolites Protect Against Metabolic Dysfunction-Associated Steatotic Liver Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Circulating β-Hydroxybutyrate in Glycemic Progression and Diabetic Cardiomyopathy: Adaptive Signal or Maladaptive Substrate?International journal of molecular sciences · 2026Review
- Metabolomic and lipidomic plasma profiles according to metabolic dysfunction-associated steatotic liver diseases (MASLD) stages in the absence of type 2 diabetes (T2D).Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Short-term time-restricted feeding improves metabolic rhythms and liver mitochondrial bioenergetic function in high-fat diet-fed mice.Function (Oxford, England) · 2026Article
- Dietary Supplementation of L-Carnosine Attenuates High Starch-Induced Disorders of Carbohydrate and Lipid Metabolisms in Zebrafish.International journal of molecular sciences · 2026Article
- Lactobacillus protects against lead-induced hepatotoxicity by preserving the gut barrier and microbiota remodeling.BMC microbiology · 2026Article
- The impact of lipid-rich nutrition on ketogenesis and muscle weakness in sepsis.Intensive care medicine experimental · 2026Article
- Quantifying endogenous and tracer-derived ketone bodies using a dual-label UHPLC-MS/MS method.Talanta · 2026Article
- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- Article
- Higher visceral fat area is inversely associated with ketosis in Chinese patients with type 2 diabetes mellitus: a cross-sectional study.Frontiers in endocrinology · 2026Article
- Functional and muscle recovery after critical illness: current and future nutritional, physical and metabolic strategies.Annals of intensive care · 2026Review
- Mitochondrial medicine in obesity: a scoping review.Open medicine (Warsaw, Poland) · 2026Review
- Association between ketone body levels and chronic liver disease: Epidemiological studies and potential mechanisms.AIMS public health · 2026Review
59 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, and potentially morbid, disease that affects one-third of the U.S. population. Normal liver safely accommodates lipid excess during fasting or carbohydrate restriction by increasing their oxidation to acetyl-CoA and ketones, yet lipid excess during NAFLD leads to hyperglycemia and, in some, steatohepatitis. To examine potential mechanisms, flux through pathways of hepatic oxidative metabolism and gluconeogenesis were studied using five simultaneous stable isotope tracers in ketotic (24-hour fast) individuals with a wide range of hepatic triglyceride contents (0-52%). Ketogenesis was progressively impaired as hepatic steatosis and glycemia worsened. Conversely, the alternative pathway for acetyl-CoA metabolism, oxidation in the tricarboxylic (TCA) cycle, was upregulated in NAFLD as ketone production diminished and positively correlated with rates of gluconeogenesis and plasma glucose concentrations. Increased respiration and energy generation that occurred in liver when β-oxidation and TCA cycle activity were coupled may explain these findings, inasmuch as oxygen consumption was higher during fatty liver and highly correlated with gluconeogenesis. These findings demonstrate that increased glucose production and hyperglycemia in NAFLD is not a consequence of acetyl-CoA production per se, but how acetyl-CoA is further metabolized in liver.
Indexed as
Identifiers
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.