Disrupting AMPK-glycogen binding in mice increases carbohydrate utilization and reduces exercise capacity
Journal article
Janzen, Natalie R., Whitfield, Jamie, Murray-Segal, Lisa, Kemp, Bruce E., Hawley, John A. and Hoffman, Nolan J.. (2022). Disrupting AMPK-glycogen binding in mice increases carbohydrate utilization and reduces exercise capacity. Frontiers in Physiology. 13, p. 859246. https://doi.org/10.3389/fphys.2022.859246
Authors | Janzen, Natalie R., 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) is a central regulator of cellular energy balance and metabolism and binds glycogen, the primary storage form of glucose in liver and skeletal muscle. The effects of disrupting whole-body AMPK-glycogen interactions on exercise capacity and substrate utilization during exercise in vivo remain unknown. We used male whole-body AMPK double knock-in (DKI) mice with chronic disruption of AMPK-glycogen binding to determine the effects of DKI mutation on exercise capacity, patterns of whole-body substrate utilization, and tissue metabolism during exercise. Maximal treadmill running speed and whole-body energy utilization during submaximal running were determined in wild type (WT) and DKI mice. Liver and skeletal muscle glycogen and skeletal muscle AMPK α and β2 subunit content and signaling were assessed in rested and maximally exercised WT and DKI mice. Despite a reduced maximal running speed and exercise time, DKI mice utilized similar absolute amounts of liver and skeletal muscle glycogen compared to WT. DKI skeletal muscle displayed reduced AMPK α and β2 content versus WT, but intact relative AMPK phosphorylation and downstream signaling at rest and following exercise. During submaximal running, DKI mice displayed an increased respiratory exchange ratio, indicative of greater reliance on carbohydrate-based fuels. In summary, whole-body disruption of AMPK-glycogen interactions reduces maximal running capacity and skeletal muscle AMPK α and β2 content and is associated with increased skeletal muscle glycogen utilization. These findings highlight potential unappreciated roles for AMPK in regulating tissue glycogen dynamics and expand AMPK’s known roles in exercise and metabolism. |
Keywords | AMP-activated protein kinase; carbohydrate binding module; glycogen; skeletal muscle; exercise; energy utilization; metabolism |
Year | 2022 |
Journal | Frontiers in Physiology |
Journal citation | 13, p. 859246 |
Publisher | Frontiers Research Foundation |
ISSN | 1664-042X |
Digital Object Identifier (DOI) | https://doi.org/10.3389/fphys.2022.859246 |
PubMed ID | 35392375 |
Scopus EID | 2-s2.0-85128183217 |
PubMed Central ID | PMC8980720 |
Open access | Published as ‘gold’ (paid) open access |
Page range | 1-14 |
Funder | Australian Catholic University (ACU) |
National Health and Medical Research Council (NHMRC) | |
Australian Research Council (ARC) | |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 22 Mar 2022 |
Publication process dates | |
Accepted | 03 Mar 2022 |
Deposited | 03 Feb 2023 |
ARC Funded Research | This output has been funded, wholly or partially, under the Australian Research Council Act 2001 |
Grant ID | 1068813 |
1085460 | |
DP170101196 |
https://acuresearchbank.acu.edu.au/item/8yqq0/disrupting-ampk-glycogen-binding-in-mice-increases-carbohydrate-utilization-and-reduces-exercise-capacity
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Publisher's version
OA_Janzen_2022_Disrupting_AMPK_glycogen_binding_in_mice.pdf | |
License: CC BY 4.0 | |
File access level: Open |
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