ArticleHuman molecular genetics2020
The signaling pathways implicated in impairment of hepatic autophagy in glycogen storage disease type Ia.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Fabry disease cardiomyopathy: A state-of-the-art review.Progress in cardiovascular diseasesPooled it
- Hepatocyte-specific Cas9-mediated editing of G6pc and Slc37a4 elicits comparable biochemical and regulatory responses between glycogen storage disease (GSD) type Ia and Ib mice.Molecular metabolism · 2026Article
- Preventive and Ameliorative Effects of Alanine Supplementation on High-Fat Diet-Induced Obesity and Metabolic Dysfunction via the Gut-Liver-Adipose Axis in C57BL/6J Mice.Foods (Basel, Switzerland) · 2026Article
- Generation of a glycogen storage disease mouse model with fatty liver and its treatment by PPAR-α agonist bezafibrate.Frontiers in pharmacology · 2026Article
- Does Autophagy have a Role in the Pathogenesis of Pediatric Hepatic Steatosis?Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Bufei Yishen formula protects the airway epithelial barrier and ameliorates COPD by enhancing autophagy through the Sirt1/AMPK/Foxo3 signaling pathway.Chinese medicine · 2024Article
- Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy.Frontiers in pharmacology · 2024Review
- Gene therapy for glycogen storage diseases.Journal of inherited metabolic disease · 2024Review
- Genome editing usingMolecular therapy. Methods & clinical development · 2023Article
- Mitochondrial reprogramming in peripheral blood mononuclear cells of patients with glycogen storage disease type Ia.Genes & nutrition · 2023Article
- Molecular mechanism underlying impaired hepatic autophagy in glycogen storage disease type Ib.Human molecular genetics · 2023Article
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- [Glucose-6 phosphatase catalytic subunit inhibits the proliferation of liver cancer cells by inducing cell cycle arrest].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Article
- Exosomal MicroRNAs as Potential Biomarkers of Hepatic Injury and Kidney Disease in Glycogen Storage Disease Type Ia Patients.International journal of molecular sciences · 2021Article
- Gene therapy using a novel G6PC-S298C variant enhances the long-term efficacy for treating glycogen storage disease type Ia.Biochemical and biophysical research communications · 2020Article
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6 authors at 1 institution in 1 country.
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Abstract
Glucose-6-phosphatase-α (G6Pase-α or G6PC) deficiency in glycogen storage disease type-Ia (GSD-Ia) leads to impaired hepatic autophagy, a recycling process important for cellular metabolism and homeostasis. Autophagy can be regulated by several energy sensing pathways, including sirtuin 1 (SIRT1), forkhead box O (FoxO), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-α (PPAR-α), and mammalian target of rapamycin (mTOR). Using 10-day old global G6pc-deficient (G6pc-/-) mice, hepatic autophagy impairment was attributed to activation of mTOR and inhibition of AMPK signaling. In other studies, using adult liver-specific G6pc-deficient mice at both pre-tumor and tumor stages, hepatic autophagy impairment was attributed to downregulation of SIRT1 signaling and mTOR was not implicated. In this study, we provide a detailed analysis of the major autophagy pathways in young G6pc-/- mice over the first 4 weeks of life. We show that impaired SIRT1, FoxO3a, AMPK, and PPAR-α signaling are responsible for autophagy impairment but mTOR is involved minimally. Hepatic SIRT1 overexpression corrects defective autophagy, restores the expression of FoxO3a and liver kinase B1 but fails to normalize impaired PPAR-α expression or metabolic abnormalities associated with GSD-Ia. Importantly, restoration of hepatic G6Pase-α expression in G6pc-/- mice corrects defective autophagy, restores SIRT1/FoxO3a/AMPK/PPAR-α signaling and rectifies metabolic abnormalities. Taken together, these data show that hepatic autophagy impairment in GSD-Ia is mediated by downregulation of SIRT1/FoxO3a/AMPK/PPAR-α signaling.
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