ArticlePLoS genetics2017
Downregulation of SIRT1 signaling underlies hepatic autophagy impairment in glycogen storage disease type Ia.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Fabry disease cardiomyopathy: A state-of-the-art review.Progress in cardiovascular diseasesPooled it
- SIRT1 in Neurodegenerative Diseases: Molecular Mechanisms, Disease Relevance, and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- 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
- Lipophagy in disease: signaling control, organelle communication, and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- The ATG14: multi-layer autophagy control and an emerging therapeutic target in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- TAZ WW Domain-Mediated Regulation of Gluconeogenesis and Tumorigenesis in Hepatocellular Carcinoma through Interaction with the Glucocorticoid Receptor.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- Linking SIRT1 Variants to Metabolic and Cardiovascular Phenotypes: Insights from Population Genetics and In Silico Structural Analysis.Cell biochemistry and biophysics · 2026Review
- Article
- Liver as a key organ for systemic antimicrobial defense.Hepatology communications · 2025Review
- SIRT1 as a potential target for age-related eye diseases: mechanisms and therapeutic strategies.Human cell · 2025Review
- Rejuvenation of Senescent Cells, In Vitro and In Vivo, by Low-Frequency Ultrasound.Aging cell · 2025Article
- Autophagy and the peroxisome proliferator-activated receptor signaling pathway: A molecular ballet in lipid metabolism and homeostasis.Molecular and cellular biochemistry · 2025Review
- Autophagy in Muscle Regeneration: Mechanisms, Targets, and Therapeutic Perspective.International journal of molecular sciences · 2024Review
- Mitochondrial Dysfunction in Glycogen Storage Disorders (GSDs).Biomolecules · 2024Review
- Deficiency of endothelial sirtuin1 in mice stimulates skeletal muscle insulin sensitivity by modifying the secretome.Nature communications · 2023Article
- The role of ChREBP in carbohydrate sensing and NAFLD development.Nature reviews. Endocrinology · 2023Review
- Molecular mechanism underlying impaired hepatic autophagy in glycogen storage disease type Ib.Human molecular genetics · 2023Article
- Gene therapy and genome editing for type I glycogen storage diseases.Frontiers in molecular medicine · 2023Review
- Novel Role of the SIRT1 in Endocrine and Metabolic Diseases.International journal of biological sciences · 2023Review
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
A deficiency in glucose-6-phosphatase-α (G6Pase-α) in glycogen storage disease type Ia (GSD-Ia) leads to impaired glucose homeostasis and metabolic manifestations including hepatomegaly caused by increased glycogen and neutral fat accumulation. A recent report showed that G6Pase-α deficiency causes impairment in autophagy, a recycling process important for cellular metabolism. However, the molecular mechanism underlying defective autophagy is unclear. Here we show that in mice, liver-specific knockout of G6Pase-α (L-G6pc-/-) leads to downregulation of sirtuin 1 (SIRT1) signaling that activates autophagy via deacetylation of autophagy-related (ATG) proteins and forkhead box O (FoxO) family of transcriptional factors which transactivate autophagy genes. Consistently, defective autophagy in G6Pase-α-deficient liver is characterized by attenuated expressions of autophagy components, increased acetylation of ATG5 and ATG7, decreased conjugation of ATG5 and ATG12, and reduced autophagic flux. We further show that hepatic G6Pase-α deficiency results in activation of carbohydrate response element-binding protein, a lipogenic transcription factor, increased expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), a lipid regulator, and suppressed expression of PPAR-α, a master regulator of fatty acid β-oxidation, all contributing to hepatic steatosis and downregulation of SIRT1 expression. An adenovirus vector-mediated increase in hepatic SIRT1 expression corrects autophagy defects but does not rectify metabolic abnormalities associated with G6Pase-α deficiency. Importantly, a recombinant adeno-associated virus (rAAV) vector-mediated restoration of hepatic G6Pase-α expression corrects metabolic abnormalities, restores SIRT1-FoxO signaling, and normalizes defective autophagy. Taken together, these data show that hepatic G6Pase-α deficiency-mediated down-regulation of SIRT1 signaling underlies defective hepatic autophagy in GSD-Ia.
Indexed as
Identifiers
What OpenQuestion holds
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.