2026-04-13T15:19:41Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1773042025-12-05T09:23:22Zcom_2072_1057col_2072_478799col_2072_478917

00925njm 22002777a 4500 dc Nilsson, Elisabeth C. author Long, Yun Chau author Martinsson, Sofia author Glund, Stephan author García-Roves, Pablo M. (Pablo Miguel) author Svensson, L. Thomas author Andersson, Leif author Zierath, Juleen R. author Mahlapuu, Margit author 2021-05-14T13:32:37Z 2021-05-14T13:32:37Z 2006-03-17 2021-05-14T13:32:37Z AMP-activated protein kinase (AMPK) is an evolutionarily conserved heterotrimer important for metabolic sensing in all eukaryotes. The muscle-specific isoform of the regulatory gamma-subunit of the kinase, AMPK gamma3, has an important role in glucose uptake, glycogen synthesis, and fat oxidation in white skeletal muscle, as previously demonstrated by physiological characterization of AMPK gamma3 mutant (R225Q) transgenic (TgPrkag3(225Q)) and gamma3 knock-out (Prkag3(-/-)) mice. We determined AMPK gamma3-dependent regulation of gene expression by analyzing global transcription profiles in glycolytic skeletal muscle from gamma3 mutant transgenic and knock-out mice using oligonucleotide microarray technology. Evidence is provided for coordinated and reciprocal regulation of multiple key components in glucose and fat metabolism, as well as skeletal muscle ergogenics in TgPrkag3(225Q) and Prkag3(-/-) mice. The differential gene expression profile was consistent with the physiological differences between the models, providing a molecular mechanism for the observed phenotype. The striking pattern of opposing transcriptional changes between TgPrkag3(225Q) and Prkag3(-/-) mice identifies differentially expressed targets being truly regulated by AMPK and is consistent with the view that R225Q is an activating mutation, in terms of its downstream effects. Additionally, we identified a wide array of novel targets and regulatory pathways for AMPK in skeletal muscle. Metabolisme Esquelet humà Músculs Proteïnes quinases Metabolism Human skeleton Muscles Protein kinases Opposite transcriptional regulation in skeletal muscle of AMP-activated protein kinase gamma3 R225Q transgenic versus knock-out mice