Pharmacological AMPK activation induces transcriptional responses congruent to exercise in skeletal and cardiac muscle, adipose tissues and liver

PloS One
Eric S MuiseIyassu K Sebhat

Abstract

Physical activity promotes metabolic and cardiovascular health benefits that derive in part from the transcriptional responses to exercise that occur within skeletal muscle and other organs. There is interest in discovering a pharmacologic exercise mimetic that could imbue wellness and alleviate disease burden. However, the molecular physiology by which exercise signals the transcriptional response is highly complex, making it challenging to identify a single target for pharmacological mimicry. The current studies evaluated the transcriptome responses in skeletal muscle, heart, liver, and white and brown adipose to novel small molecule activators of AMPK (pan-activators for all AMPK isoforms) compared to that of exercise. A striking level of congruence between exercise and pharmacological AMPK activation was observed across the induced transcriptome of these five tissues. However, differences in acute metabolic response between exercise and pharmacologic AMPK activation were observed, notably for acute glycogen balances and related to the energy expenditure induced by exercise but not pharmacologic AMPK activation. Nevertheless, intervention with repeated daily administration of short-acting activation of AMPK was found to miti...Continue Reading

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Citations

Jul 14, 2019·The Journal of Pharmacology and Experimental Therapeutics·Xiaoyan ZhouMaarten Hoek
Jul 8, 2020·Nature Reviews. Endocrinology·Sean L McGee, Mark Hargreaves
Nov 27, 2020·IScience·Derek W StouthVladimir Ljubicic
Jun 7, 2021·Biogerontology·Aleksei G Golubev
Jun 10, 2021·Nature Reviews. Drug Discovery·Carolina Gubert, Anthony J Hannan
Jun 3, 2021·Cells·Maimoona Shahid BhuttaRonen Borenstein
Sep 22, 2021·Molecular Cell·Elijah Trefts, Reuben J Shaw

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Datasets Mentioned

BETA
GPL9734
GSE92719

Methods Mentioned

BETA
chip
NMR
ELISA

Software Mentioned

Affymetrix
Graphpad
Array Studio
Graphpad Prism

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