ArticleScientific reports2016
PGC-1α Promotes Ureagenesis in Mouse Periportal Hepatocytes through SIRT3 and SIRT5 in Response to Glucagon.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Nitrogen Isotope Effects in Urea Metabolism: From Biochemistry toInternational journal of molecular sciences · 2026Review
- The expanding landscape of the glucagon signaling network: mechanisms and outcomes.Endocrinology · 2026Review
- Hepatic PKA Mediates Liver and Pancreatic α-Cell Cross Talk.Diabetes · 2025Article
- SIRT5: a potential target for discovering bioactive natural products.Journal of natural medicines · 2025Review
- A Two-Hour Fetal Glucagon Infusion Stimulates Hepatic Catabolism of Amino Acids in Fetal Sheep.International journal of molecular sciences · 2025Article
- Female glucagon receptor knockout mice are prone to steatosis but resistant to weight gain when fed a MASH-promoting GAN diet and a high-fat diet.Physiological reports · 2025Article
- The Antiaging and Antioxidative Effects of a Combination of Resveratrol and High-Intensity Interval Training on the Frontal Lobe in Aged Rats: The Role of SIRTS 4, SIRTS 5, SOD1, and SOD2.Oxidative medicine and cellular longevity · 2025Article
- The role of SIRT3 in homeostasis and cellular health.Frontiers in cellular neuroscience · 2024Review
- CPS1 augments hepatic glucagon response through CaMKII/FOXO1 pathway.Frontiers in pharmacology · 2024Article
- Effects of green light-emitting diode irradiation on hepatic differentiation of hepatocyte-like cells generated from human adipose-derived mesenchymal cells.Scientific reports · 2023Article
- Lipid nanoparticle-targeted mRNA formulation as a treatment for ornithine-transcarbamylase deficiency model mice.Molecular therapy. Nucleic acids · 2023Article
- Role of SIRT3 in neurological diseases and rehabilitation training.Metabolic brain disease · 2023Review
- Protein Targeting to Glycogen (PTG): A Promising Player in Glucose and Lipid Metabolism.Biomolecules · 2022Review
- Opposing effects of chronic glucagon receptor agonism and antagonism on amino acids, hepatic gene expression, and alpha cells.iScience · 2022Article
- Cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor function.Frontiers in immunology · 2022Article
- Review
- CPS1: Looking at an ancient enzyme in a modern light.Molecular genetics and metabolism · 2020Review
- Impaired mitochondrial medium-chain fatty acid oxidation drives periportal macrovesicular steatosis in sirtuin-5 knockout mice.Scientific reports · 2020Article
- Acetylation of Phenylalanine Hydroxylase and Tryptophan 2,3-Dioxygenase Alters Hepatic Aromatic Amino Acid Metabolism in Weaned Piglets.Metabolites · 2020Article
- SWI/SNF complex subunit BAF60a represses hepatic ureagenesis through a crosstalk between YB-1 and PGC-1α.Molecular metabolism · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excess ammonia is produced during fasting when amino acids are used for glucogenesis. Together with ureagenesis, glucogenesis occurs in periportal hepatocytes mediated mainly through the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). In vivo experiments showed that fasting strongly stimulated mice glucagon secretion, hepatic PGC-1α, sirtuin 3 (SIRT3) and sirtuin 5 (SIRT5) expression and ureagenesis enzymatic activity such as carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamoylase (OTC). Interestingly, (15)N-labeled urea and (13)C-labeled glucose production in wild-type mice were significantly increased compared with PGC-1α null mice by [(15)N,(13)C]alanine perfused liver. Glucagon significantly stimulated ureagenesis, expression of SIRT3, SIRT5 and the activities of CPS1 and OCT but did not stimulate PGC-1α silencing hepatocytes in mice periportal hepatocytes. Contrarily, PGC-1α overexpression significantly increased the expression of SIRT3, SIRT5 and the activities of CPS1 and OTC, but induced no significant changes in CPS1 and OTC expression. Morever, SIRT3 directly deacetylates and upregulates the activity of OTC, while SIRT5 deacetylates and stimulates the activity of CPS1. During fasting, PGC-1α facilitates ureagenesis in mouse periportal hepatocytes by deacetylating CPS1 and OTC modulated by mitochondrial deacetylase, SIRT3 and SIRT5. This mechanism may be relevant to ammonia detoxification and metabolic homeostasis in liver during fasting.
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