Genetic loss of AMPK-glycogen binding destabilises AMPK and disrupts metabolism
Nolan J Hoffman, Jamie Whitfield, Natalie R Janzen, Mehdi R Belhaj, Sandra Galic, Lisa Murray-Segal, William J Smiles, Naomi XY Ling, Toby A Dite, John W Scott, Jonathan S Oakhill, Robert Brink, Bruce E Kemp, John A Hawley
MOLECULAR METABOLISM | ELSEVIER | Published : 2020
OBJECTIVE: Glycogen is a major energy reserve in liver and skeletal muscle. The master metabolic regulator AMP-activated protein kinase (AMPK) associates with glycogen via its regulatory β subunit carbohydrate-binding module (CBM). However, the physiological role of AMPK-glycogen binding in energy homeostasis has not been investigated in vivo. This study aimed to determine the physiological consequences of disrupting AMPK-glycogen interactions. METHODS: Glycogen binding was disrupted in mice via whole-body knock-in (KI) mutation of either the AMPK β1 (W100A) or β2 (W98A) isoform CBM. Systematic whole-body, tissue and molecular phenotyping was performed in KI and respective wild-type (WT) mic..View full abstract
Awarded by Australian Catholic University Research Funding (ACURF) Early Career Researcher Grant
Awarded by National Health and Medical Research Council of Australia (NHMRC)
Awarded by NHMRC Fellowship
This work was supported by an Australian Catholic University Research Funding (ACURF) Early Career Researcher Grant awarded to N.J.H. (2016000348), National Health and Medical Research Council of Australia (NHMRC) project grant (1085460) awarded to B.E.K and S.G., and NHMRC Fellowship to B.E.K. (1078752). We thank the Mouse Engineering Garvan/ABR (MEGA) Facility and St. Vincent's BioResources Centre staff for their assistance with mouse generation and husbandry, respectively, and Fawzan Dinnunhan for assistance with gene expression analysis. This study utilised the Australian Phenomics Network Histopathology and Organ Pathology Service, University of Melbourne.