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Pharmacological AMPK activation induces transcriptional responses congruent to exercise in skeletal and cardiac muscle, adipose tissues and liver
- Source :
- PLoS ONE, Vol 14, Iss 2, p e0211568 (2019), PLoS ONE
- Publication Year :
- 2019
- Publisher :
- Public Library of Science (PLoS), 2019.
-
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 mitigate hyperglycemia and hyperinsulinemia in four rodent models of metabolic disease and without the cardiac glycogen accretion noted with sustained pharmacologic AMPK activation. These findings affirm that activation of AMPK is a key node governing exercise mediated transcription and is an attractive target as an exercise mimetic.
- Subjects :
- 0301 basic medicine
Glycogens
Glycobiology
Adipose tissue
Cardiovascular Medicine
AMP-Activated Protein Kinases
Biochemistry
Transcriptome
chemistry.chemical_compound
0302 clinical medicine
Medicine and Health Sciences
Hyperinsulinemia
Homeostasis
Public and Occupational Health
Musculoskeletal System
Multidisciplinary
Glycogen
Organic Compounds
Pharmaceutics
Muscles
Monosaccharides
Fatty Acids
Cardiac muscle
Heart
Sports Science
Chemistry
medicine.anatomical_structure
Adipose Tissue
Liver
Physical Sciences
Medicine
Anatomy
Oxidation-Reduction
Research Article
medicine.medical_specialty
Drug Administration
Science
DNA transcription
Carbohydrates
Cardiovascular Pharmacology
03 medical and health sciences
Drug Therapy
Physical Conditioning, Animal
Internal medicine
Genetics
medicine
Animals
Sports and Exercise Medicine
Muscle, Skeletal
Exercise
Pharmacology
business.industry
Myocardium
Organic Chemistry
Chemical Compounds
Biology and Life Sciences
Skeletal muscle
AMPK
Physical Activity
medicine.disease
Enzyme Activation
Mice, Inbred C57BL
Glucose
030104 developmental biology
Endocrinology
Skeletal Muscles
Gene Expression Regulation
chemistry
Physical Fitness
Cardiovascular Anatomy
Gene expression
Energy Metabolism
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 14
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....1e74f669b91225dbd7a81a386f22662b