ArticleThe Journal of biological chemistry2014
Apolipoprotein A-IV reduces hepatic gluconeogenesis through nuclear receptor NR1D1.
Article in The Journal of biological chemistry, 2014. 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, 82 citations in OpenAlex.
- Plasma apolipoprotein A-IV deficiency as a proteomics-identified diagnostic biomarker for heat stroke: A prospective 2-center study.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2026Article
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- Targeting Liver Epsins Ameliorates Dyslipidemia in Atherosclerosis through Inhibition of Proprotein Convertase Subtilisin/Kexin Type 9-Mediated Low-density Lipoprotein Receptor Degradation.bioRxiv : the preprint server for biology · 2025Article
- Comparative transcriptome analysis reveals genes associated with variation in liver copper concentration in Polish Merino sheep.Scientific reports · 2025Article
- Attenuation of high-fat diet-induced weight gain by apolipoprotein A4.Obesity (Silver Spring, Md.) · 2024Article
- Dietary medium-chain fatty acids reduce hepatic fat accumulation via activation of a CREBH-FGF21 axis.Molecular metabolism · 2024Article
- Apolipoprotein A-IV and its derived peptide, T55-121, improve glycemic control and increase energy expenditure.Life metabolism · 2024Article
- Genomic and Phenotypic Adaptations of Rattus tanezumi to Cold Limit Its Further Northward Expansion and Range Overlap with R. norvegicus.Molecular biology and evolution · 2024Article
- Protein disulfide isomerase cleaves allosteric disulfides in histidine-rich glycoprotein to regulate thrombosis.Nature communications · 2024Article
- Recent Advances in Hepatic Metabolic Regulation by the Nuclear Factor Rev-erbɑ.Current drug metabolism · 2024Review
- Targeting NR1D1 in organ injury: challenges and prospects.Military Medical Research · 2023Review
- Effect of dapagliflozin on proteomics and metabolomics of serum from patients with type 2 diabetes.Diabetology & metabolic syndrome · 2023Article
- Apolipoprotein A-IV-Deficient Mice in 129/SvJ Background Are Susceptible to Obesity and Glucose Intolerance.Nutrients · 2023Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Systematic review of type 1 diabetes biomarkers reveals regulation in circulating proteins related to complement, lipid metabolism, and immune response.Clinical proteomics · 2023Review
- Article
- The distinct metabolism between large and small HDL indicates unique origins of human apolipoprotein A4.JCI insight · 2023Article
- Single-cell RNA sequencing reveals a novel inhibitory effect of ApoA4 on NAFL mediated by liver-specific subsets of myeloid cells.Frontiers in immunology · 2022Article
- HDL and Diabetes.Advances in experimental medicine and biology · 2022Article
- Depression Augments Plasma APOA4 without Changes of Plasma Lipids and Glucose in Female Adolescents Carrying G Allele of APOA4 rs5104.Journal of molecular neuroscience : MN · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
We showed recently that apoA-IV improves glucose homeostasis by enhancing pancreatic insulin secretion in the presence of elevated levels of glucose. Therefore, examined whether apolipoprotein A-IV (apoA-IV) also regulates glucose metabolism through the suppression of hepatic gluconeogenesis. The ability of apoA-IV to lower gluconeogenic gene expression and glucose production was measured in apoA-IV(-/-) and wild-type mice and primary mouse hepatocytes. The transcriptional regulation of Glc-6-Pase and phosphoenolpyruvate carboxykinase (PEPCK) by apoA-IV was determined by luciferase activity assay. Using bacterial two-hybrid library screening, NR1D1 was identified as a putative apoA-IV-binding protein. The colocalization and interaction between apoA-IV and NR1D1 were confirmed by immunofluorescence, in situ proximity ligation assay, and coimmunoprecipitation. Enhanced recruitment of NR1D1 and activity by apoA-IV to Glc-6-Pase promoter was verified with ChIP and a luciferase assay. Down-regulation of apoA-IV on gluconeogenic genes is mediated through NR1D1, as illustrated in cells with NR1D1 knockdown by siRNA. We found that apoA-IV suppresses the expression of PEPCK and Glc-6-Pase in hepatocytes; decreases hepatic glucose production; binds and activates nuclear receptor NR1D1 and stimulates NR1D1 expression; in cells lacking NR1D1, fails to inhibit PEPCK and Glc-6-Pase gene expression; and stimulates higher hepatic glucose production and higher gluconeogenic gene expression in apoA-IV(-/-) mice. We conclude that apoA-IV inhibits hepatic gluconeogenesis by decreasing Glc-6-Pase and PEPCK gene expression through NR1D1. This novel regulatory pathway connects an influx of energy as fat from the gut (and subsequent apoA-IV secretion) with inhibition of hepatic glucose production.
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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.