ArticleAging and disease2020
β-Hydroxybutyrate Suppresses Lipid Accumulation in Aged Liver through GPR109A-mediated Signaling.
Article in Aging and disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 60 citations in OpenAlex.
- Article
- β-Hydroxybutyrate Attenuates Diabetic Kidney Disease Partially Via β-hydroxybutyrylation of Nrf2.Inflammation · 2026Article
- GPR109a-AMPK axis mediates the Attenuation of uric acid-induced M1 macrophage polarization by β-hydroxybutyrate from Lacticaseibacillus rhamnosus M2b.Scientific reports · 2026Article
- Calorie Restriction Modulates Gene Expression of Il19 and Il24 during Renal Aging.Annals of geriatric medicine and research · 2026Article
- Review
- Review
- Association between ketone body levels and chronic liver disease: Epidemiological studies and potential mechanisms.AIMS public health · 2026Review
- The multifaceted roles of ketones in physiology.Experimental physiology · 2026Review
- Hydroxycarboxylic acid receptor 2 (GPR109A) and retinopathies: pathways and prospects.Frontiers in medicine · 2026Review
- Exercise-induced β-hydroxybutyrate contributes to cognitive improvement in aging mice.Journal of sport and health science · 2025Article
- β-Hydroxybutyrate enhances malate dehydrogenase 2 β-hydroxybutyrylation to alleviate hepatic steatosis in MASLD.Cellular and molecular life sciences : CMLS · 2025Article
- Ketone metabolites in metabolic dysfunction-associated steatotic liver disease progression: optimizing keto-therapeutic strategies.American journal of physiology. Endocrinology and metabolism · 2025Review
- Unraveling the Translational Relevance of β-Hydroxybutyrate as an Intermediate Metabolite and Signaling Molecule.International journal of molecular sciences · 2025Review
- Article
- Aerobic Exercise Delays Age-Related Sarcopenia in Mice via Alleviating Imbalance in Mitochondrial Quality Control.Metabolites · 2025Article
- Metabolomics in cardiometabolic diseases: Key biomarkers and therapeutic implications for insulin resistance and diabetes.Journal of internal medicine · 2025Review
- Article
- Neuroprotective effect of niacin in a rat model of obesity induced by high-fat-rich diet.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Gpr109A in TAMs promoted hepatocellular carcinoma via increasing PKA/PPARγ/MerTK/IL-10/TGFβ induced M2c polarization.Scientific reports · 2025Article
- P46Shc Inhibits Mitochondrial ACAA2 Thiolase, Exacerbating Mitochondrial Injury and Inflammation in Aging Livers.The American journal of pathology · 2025Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dietary interventions such as prolonged calorie restriction (CR) and intermittent fasting provide health benefits including a reduction in the inflammatory burden and regulation of energy metabolism. During CR, β-hydroxybutyrate (BHB) level is elevated in the serum. BHB is a ligand of GPR109A, which inhibits lipolysis and exerts anti-inflammatory effects on cells. During aging, comorbidities related to dyslipidemia are significantly associated with fatty liver. However, the underlying mechanisms of BHB in hepatic ER stress and dyslipidemia are unclear and remain to be elucidated. Here, we used aged rats that were administered with BHB and compared the modulatory effects of BHB through the GPR109A/AMPK pathway on the hepatic endoplasmic reticulum (ER) stress and lipid accumulation to CR rats. BHB caused suppression of hepatic ER stress and lipid accumulation through GPR109A/AMPK pathway in the aged rats. Aged rats of both treatment groups showed reduced cAMP level and PKA phosphorylation. Furthermore, AMPK-Ser173 phosphorylation via PKA was decreased, whereas AMPK-Thr172 phosphorylation was increased by BHB and CR. Further supporting evidence was provided in HepG2 cells that BHB inhibited ER stress and lipid accumulation induced by palmitate. These results suggest that BHB activates GPR109A and regulates the activation of AMPK. These findings were further confirmed by GPR109A-siRNA transfection
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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.