ArticleProceedings of the National Academy of Sciences of the United States of America2022
The phosphorylation of AMPKβ1 is critical for increasing autophagy and maintaining mitochondrial homeostasis in response to fatty acids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 36 citations in OpenAlex.
- Vanadium(IV)-chlorodipicolinate alleviates hepatic steatosis via the AMPK/PGC-1α/CPT1a axis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- Multi-omics Mendelian randomization and experimental validation identify PRKAB1 as a regulator of phosphatidylcholine metabolism in IBD.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Mitophagy in Metabolic Dysfunction-Associated Fatty Liver Disease: Mechanisms, Regulatory Networks, and Therapeutic Perspectives.Inflammation · 2026Review
- Hu Gan Tang Ameliorates Lipid Deposition of Metabolic-Associated Fatty Liver Disease by Promoting Autophagy Through the AMPK/mTOR Pathway.Chemistry & biodiversity · 2026Article
- Targeting the Gut-Liver Mitochondria Axis in MASLD: Mechanisms and Therapeutic Perspectives.Current medical science · 2026Review
- Review
- A Global Perspective on Metabolic Dysfunction-Associated Steatotic Liver Disease: From Molecular Mechanisms to Therapeutic Strategy Innovation.Nutrients · 2026Review
- Hic-5 promotes the progression of nonalcoholic steatohepatitis by regulating hepatocellular fatty acid metabolism through the PTEN/PGE2/EP4 axis.Molecular biomedicine · 2026Article
- Therapeutic targeting of the AMPK-Has1 complex formation ameliorates metabolic dysfunction-associated steatohepatitis in mice.Theranostics · 2026Article
- Intermittent fasting triggers interorgan communication to improve the progression of diabetic osteoporosis.Gut microbes · 2025Article
- Mitophagy as a pivotal axis in non‑alcoholic fatty liver disease: From pathogenic mechanisms to therapeutic strategies (Review).Molecular medicine reports · 2025Review
- AMPK/SIRT1/PGC-1α Signaling Pathway: Molecular Mechanisms and Targeted Strategies From Energy Homeostasis Regulation to Disease Therapy.CNS neuroscience & therapeutics · 2025Review
- The AMPK Pathway: Molecular Rejuvenation of Metabolism and Mitochondria.Annual review of cell and developmental biology · 2025Review
- MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025Review
- Ketogenic diet ameliorates MASLD via balancing mitochondrial dynamics and improving mitochondrial dysfunction.Nutrition & diabetes · 2025Article
- An integrated proteomics approach identifies phosphorylation sites on viral and host proteins that regulate West Nile virus infection.Cell reports · 2025Article
- [Research progress on glycolipid metabolism of Sertoli cell in the development of spermatogenic cell].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Review
- Sensing of Long-Chain Fatty Acyl-CoA Esters by AMPK.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Research progress on AMPK in the pathogenesis and treatment of MASLD.Frontiers in immunology · 2025Review
- The molecular determinants regulating redox signaling in diabetic endothelial cells.Frontiers in pharmacology · 2025Review
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Fatty acids are vital for the survival of eukaryotes, but when present in excess can have deleterious consequences. The AMP-activated protein kinase (AMPK) is an important regulator of multiple branches of metabolism. Studies in purified enzyme preparations and cultured cells have shown that AMPK is allosterically activated by small molecules as well as fatty acyl-CoAs through a mechanism involving Ser108 within the regulatory AMPK β1 isoform. However, the in vivo physiological significance of this residue has not been evaluated. In the current study, we generated mice with a targeted germline knock-in (KI) mutation of AMPKβ1 Ser108 to Ala (S108A-KI), which renders the site phospho-deficient. S108A-KI mice had reduced AMPK activity (50 to 75%) in the liver but not in the skeletal muscle. On a chow diet, S108A-KI mice had impairments in exogenous lipid-induced fatty acid oxidation. Studies in mice fed a high-fat diet found that S108A-KI mice had a tendency for greater glucose intolerance and elevated liver triglycerides. Consistent with increased liver triglycerides, livers of S108A-KI mice had reductions in mitochondrial content and respiration that were accompanied by enlarged mitochondria, suggestive of impairments in mitophagy. Subsequent studies in primary hepatocytes found that S108A-KI mice had reductions in palmitate- stimulated Cpt1a and Ppargc1a mRNA, ULK1 phosphorylation and autophagic/mitophagic flux. These data demonstrate an important physiological role of AMPKβ1 Ser108 phosphorylation in promoting fatty acid oxidation, mitochondrial biogenesis and autophagy under conditions of high lipid availability. As both ketogenic diets and intermittent fasting increase circulating free fatty acid levels, AMPK activity, mitochondrial biogenesis, and mitophagy, these data suggest a potential unifying mechanism which may be important in mediating these effects.
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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.