ArticleThe Journal of clinical investigation2014
Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
137 citing papers in PubMed, 2 syntheses or guidelines pooled it, 196 citations in OpenAlex.
- Effects of sodium-glucose cotransporter 2 inhibitors on non-alcoholic fatty liver disease in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.Journal of diabetes investigation · 2020Pooled it
- Genome Wide Association Study Identifies theJournal of the American Heart Association · 2018Pooled it
- Ketogenesis as a Metabolic Checkpoint in MASLD: Implications for Disease Progression and Therapy.Metabolites · 2026Review
- Revisiting cannabinoid receptor-2: a key regulator of hepatic steatosis, inflammatory cascades, and fibrotic progression.Archives of toxicology · 2026Review
- Circulating β-Hydroxybutyrate in Glycemic Progression and Diabetic Cardiomyopathy: Adaptive Signal or Maladaptive Substrate?International journal of molecular sciences · 2026Review
- Blood-derived gene expression profiles associated with dietary microalgae oil intake and methane emission variation in lambs.BMC genomics · 2026Article
- Hepatic ketogenesis is not required for exercise training to mitigate diet-induced liver steatosis in male mice.Function (Oxford, England) · 2026Article
- Divergent Liver and Kidney Metabolic Responses to Ketogenic, High-Fat, and Sucrose-Enriched Diets in Mice.Nutrients · 2026Article
- Cognitive impairment caused by compromised hepatic ketogenesis is prevented by endurance exercise.The Journal of physiology · 2026Article
- Article
- Metabolic and molecular evaluation of Moringa oleifera-supplemented ketogenic meal replacement in healthy C57BL/6 mice.Scientific reports · 2026Article
- Hepatic ketogenesis supports liver lipid homeostasis during acute exercise but is not required for exercise training to mitigate liver steatosis in mice.bioRxiv : the preprint server for biology · 2026Article
- Hepatic HMGCS2-derived β-hydroxybutyrate attenuates hippocampal insulin resistance and neuroinflammation to promote MASLD-induced cognitive function.Communications biology · 2026Article
- Association between ketone body levels and chronic liver disease: Epidemiological studies and potential mechanisms.AIMS public health · 2026Review
- The mechanisms underlying COVID-19 induced insulin resistance: a narrative review.Frontiers in endocrinology · 2026Review
- BDH1-Dependent Ketone Body Metabolism Maintains Müller Cell Homeostasis and Retinal Function.bioRxiv : the preprint server for biology · 2025Article
- Gut microbiota regulates hepatic ketogenesis and lipid accumulation in ketogenic diet-induced hyperketonemia by disrupting bile acid metabolism.Gut microbes · 2025Article
- Ketone metabolites in metabolic dysfunction-associated steatotic liver disease progression: optimizing keto-therapeutic strategies.American journal of physiology. Endocrinology and metabolism · 2025Review
- Mitonuclear Communication in Stem Cell Function.Cell proliferation · 2025Review
- Association between serum beta-hydroxybutyrate levels and risk of type 2 diabetes mellitus in patients with impaired fasting glucose.Nutrition & diabetes · 2025Article
77 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately 1 billion individuals worldwide. However, the drivers of progressive steatohepatitis remain incompletely defined. Ketogenesis can dispose of much of the fat that enters the liver, and dysfunction in this pathway could promote the development of NAFLD. Here, we evaluated mice lacking mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2) to determine the role of ketogenesis in preventing diet-induced steatohepatitis. Antisense oligonucleotide-induced loss of HMGCS2 in chow-fed adult mice caused mild hyperglycemia, increased hepatic gluconeogenesis from pyruvate, and augmented production of hundreds of hepatic metabolites, a suite of which indicated activation of the de novo lipogenesis pathway. High-fat diet feeding of mice with insufficient ketogenesis resulted in extensive hepatocyte injury and inflammation, decreased glycemia, deranged hepatic TCA cycle intermediate concentrations, and impaired hepatic gluconeogenesis due to sequestration of free coenzyme A (CoASH). Supplementation of the CoASH precursors pantothenic acid and cysteine normalized TCA intermediates and gluconeogenesis in the livers of ketogenesis-insufficient animals. Together, these findings indicate that ketogenesis is a critical regulator of hepatic acyl-CoA metabolism, glucose metabolism, and TCA cycle function in the absorptive state and suggest that ketogenesis may modulate fatty liver disease.
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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.