ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2019
Role of ketone signaling in the hepatic response to fasting.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Acute nutritional ketosis during early recovery from aerobic exercise does not affect skeletal muscle transcriptomic response in humans.European journal of applied physiology · 2026Trial
- Ketone monoester plus high-dose glucose supplementation before exercise does not affect immediate post-exercise erythropoietin concentrations versus glucose alone.Physiological reports · 2024Trial
- Very Low Energy Ketogenic Therapy Effects on Fibrosis-Dependent Metabolic Reprogramming: A Serum NMR Pilot Study.Nutrients · 2026Article
- Hepatic ketogenesis is not required for exercise training to mitigate diet-induced liver steatosis in male mice.Function (Oxford, England) · 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
- Fasting as a Multisystem Health Modulator: A Narrative Review of Metabolic, Cardiovascular, Immune, Neurocognitive, and Psychospiritual Effects.Current nutrition reports · 2026Review
- Epigenetic Histone β-Hydroxybutyrylation Contributes to Renoprotection by β-Hydroxybutyrate in the Dahl Rat.Hypertension (Dallas, Tex. : 1979) · 2025Article
- HMGCS2 and AMACR as potential targets linking mitochondrial dysfunction and ulcerative colitis.Scientific reports · 2024Article
- The effect of intermittent fasting on preventing obesity-related early aging from a molecular and cellular perspective.Journal of medicine and life · 2024Review
- Targeting ketone body metabolism to treat fatty liver disease.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
- High-fat ketogenic diets and ketone monoester supplements differentially affect substrate metabolism during aerobic exercise.American journal of physiology. Cell physiology · 2023Review
- LONP1 targets HMGCS2 to protect mitochondrial function and attenuate chronic kidney disease.EMBO molecular medicine · 2023Article
- Prioritizing Pesticides of Potential Concern and Identifying Potential Mixture Effects in Great Lakes Tributaries Using Passive Samplers.Environmental toxicology and chemistry · 2023Article
- Microarray analysis of hub genes, non-coding RNAs and pathways in lung after whole body irradiation in a mouse model.International journal of radiation biology · 2023Article
- Metabolic and physical function are improved with lifelong 15% calorie restriction in aging male mice.Biogerontology · 2022Article
- Circadian transcriptional pathway atlas highlights a proteasome switch in intermittent fasting.Cell reports · 2022Article
- Glucagon receptor signaling at white adipose tissue does not regulate lipolysis.American journal of physiology. Endocrinology and metabolism · 2022Article
- miR-155 down-regulation protects the heart from hypoxic damage by activating fructose metabolism in cardiac fibroblasts.Journal of advanced research · 2022Article
- Hepatic metabolite responses to 4-day complete fasting and subsequent refeeding in rats.PeerJ · 2022Article
- Hepatokines and Non-Alcoholic Fatty Liver Disease: Linking Liver Pathophysiology to Metabolism.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Ketosis is a metabolic adaptation to fasting, nonalcoholic fatty liver disease (NAFLD), and prolonged exercise. β-OH butyrate acts as a transcriptional regulator and at G protein-coupled receptors to modulate cellular signaling pathways in a hormone-like manner. While physiological ketosis is often adaptive, chronic hyperketonemia may contribute to the metabolic dysfunction of NAFLD. To understand how β-OH butyrate signaling affects hepatic metabolism, we compared the hepatic fasting response in control and 3-hydroxy-3-methylglutaryl-CoA synthase II (HMGCS2) knockdown mice that are unable to elevate β-OH butyrate production. To establish that rescue of ketone metabolic/endocrine signaling would restore the normal hepatic fasting response, we gave intraperitoneal injections of β-OH butyrate (5.7 mmol/kg) to HMGCS2 knockdown and control mice every 2 h for the final 9 h of a 16-h fast. In hypoketonemic, HMGCS2 knockdown mice, fasting more robustly increased mRNA expression of uncoupling protein 2 (UCP2), a protein critical for supporting fatty acid oxidation and ketogenesis. In turn, exogenous β-OH butyrate administration to HMGCS2 knockdown mice decreased fasting UCP2 mRNA expression to that observed in control mice. Also supporting feedback at the transcriptional level, β-OH butyrate lowered the fasting-induced expression of HMGCS2 mRNA in control mice. β-OH butyrate also regulates the glycemic response to fasting. The fast-induced fall in serum glucose was absent in HMGCS2 knockdown mice but was restored by β-OH butyrate administration. These data propose that endogenous β-OH butyrate signaling transcriptionally regulates hepatic fatty acid oxidation and ketogenesis, while modulating glucose tolerance.
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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.