Mice with whole-body disruption of AMPK-glycogen binding have increased adiposity, reduced fat oxidation and altered tissue glycogen dynamics
Journal article
Janzen, Natalie, Whitfield, Jamie, Murray-Segal, Lisa, Kemp, Bruce E., Hawley, John A. and Hoffman, Nolan J.. (2021). Mice with whole-body disruption of AMPK-glycogen binding have increased adiposity, reduced fat oxidation and altered tissue glycogen dynamics. International Journal of Molecular Sciences. 22(17), p. Article: 9616. https://doi.org/10.3390/ijms22179616
Authors | Janzen, Natalie, Whitfield, Jamie, Murray-Segal, Lisa, Kemp, Bruce E., Hawley, John A. and Hoffman, Nolan J. |
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Abstract | The AMP-activated protein kinase (AMPK), a central regulator of cellular energy balance and metabolism, binds glycogen via its β subunit. However, the physiological effects of disrupting AMPK-glycogen interactions remain incompletely understood. To chronically disrupt AMPK-glycogen binding, AMPK β double knock-in (DKI) mice were generated with mutations in residues critical for glycogen binding in both the β1 (W100A) and β2 (W98A) subunit isoforms. We examined the effects of this DKI mutation on whole-body substrate utilization, glucose homeostasis, and tissue glycogen dynamics. Body composition, metabolic caging, glucose and insulin tolerance, serum hormone and lipid profiles, and tissue glycogen and protein content were analyzed in chow-fed male DKI and age-matched wild-type (WT) mice. DKI mice displayed increased whole-body fat mass and glucose intolerance associated with reduced fat oxidation relative to WT. DKI mice had reduced liver glycogen content in the fed state concomitant with increased utilization and no repletion of skeletal muscle glycogen in response to fasting and refeeding, respectively, despite similar glycogen-associated protein content relative to WT. DKI liver and skeletal muscle displayed reductions in AMPK protein content versus WT. These findings identify phenotypic effects of the AMPK DKI mutation on whole-body metabolism and tissue AMPK content and glycogen dynamics. |
Keywords | AMP-activated protein kinase; carbohydrate-binding module; glucose homeostasis; metabolism; liver; skeletal muscle |
Year | 2021 |
Journal | International Journal of Molecular Sciences |
Journal citation | 22 (17), p. Article: 9616 |
Publisher | MDPI AG |
ISSN | 1661-6596 |
Digital Object Identifier (DOI) | https://doi.org/10.3390/ijms22179616 |
PubMed ID | 34502525 |
Scopus EID | 2-s2.0-85114217188 |
PubMed Central ID | PMC8431764 |
Open access | Published as ‘gold’ (paid) open access |
Research or scholarly | Research |
Page range | 1-21 |
Funder | Australian Catholic University (ACU) |
National Health and Medical Research Council (NHMRC) | |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 05 Sep 2021 |
Publication process dates | |
Accepted | 03 Sep 2021 |
Deposited | 23 Nov 2021 |
Grant ID | NHMRC/1085460 |
NHMRC/1078752 |
https://acuresearchbank.acu.edu.au/item/8x1x3/mice-with-whole-body-disruption-of-ampk-glycogen-binding-have-increased-adiposity-reduced-fat-oxidation-and-altered-tissue-glycogen-dynamics
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Publisher's version
OA_Janzen_2021_Mice_with_whole-body_disruption_of.pdf | |
License: CC BY 4.0 | |
File access level: Open |
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