Combined pharmacological activation of AMPK and PPARδ potentiates the effects of exercise in trained mice.

Manio MC, Inoue K, Fujitani M, Matsumura S, Fushiki T

Physiological reports1 Mar 2016Cited by 26 (Europe PMC)

PMID26997622PMCIDPMC4823600DOI10.14814/phy2.12625PepBankPUB-26997622

Summary

The combined activation of the cellular energy sensor AMP-activated protein kinase (AMPK) and the nuclear transcription factor peroxisome proliferator-activated receptor delta (PPARδ) has been demonstrated to improve endurance and muscle function by mimicking the effects of exercise training. However, their combined pharmacological activation with exercise training has not been explored. Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks. AICAR treatment potentiated endurance, but the combination of AICAR and GW0742 further potentiated endurance and increased all running parameters significantly relative to exercised and nonexercised groups (138-179% and 355% increase in running time, respectively). Despite the lack of change in basal whole-body metabolism, a significant shift to fat as the main energy source with a decline in carbohydrate utilization was observed upon indirect calorimetry analysis at the period near exhaustion. Increased energy substrates before exercise, and elevated muscle nonesterified fatty acids (NEFA) and elevated muscle glycogen at exhaustion were observed together with increased PDK4 mRNA expression. Citrate synthase activity was elevated in AICAR-treated groups, while PGC-1α protein level tended to be increased in GW0742-treated groups. At exhaustion, Pgc1a was robustly upregulated together with Pdk4, Cd36, and Lpl in the muscle. A robust upregulation of Pgc1a and a downregulation in Chrebp were observed in the liver. Our data show that combined pharmacological activation of AMPK and PPARδ potentiates endurance in trained mice by transcriptional changes in muscle and liver, increased available energy substrates, delayed hypoglycemia through glycogen sparing accompanied by increased NEFA availability, and improved substrate shift from carbohydrate to fat.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study18

1 result from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In trained mice, AICAR potentiated endurance.
In plain wordsIn mice, AICAR increased endurance during exercise training.
Peptide
AICAR (acadesine)
Outcome
IncreaseEndurance with AICAR
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Exercise and physical function · Musculoskeletal
Studied dose
Dose not stated · 4 weeksAs given in this study (mouse).
Source sentences
Summary
AICAR treatment potentiated endurance,
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
Show in the study text Report a problemFND-2699762201

Studies that did not test the peptide alone17

In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking AICAR (acadesine).

02AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Efficacy outcome
In mice, AICAR with GW0742 increased running time by 138-179% versus the exercised group.
In plain wordsIn mice, AICAR with GW0742 increased running time by 138-179% compared with the exercised group.
Peptide
AICAR (acadesine)
Outcome
IncreaseCombination running time versus exercised group
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Comparator
Exercised group
Outcome group
Exercise and physical function · Musculoskeletal
Measurements
Running time increase
138 to 179%
versus exercised group
Source sentences
Summary
AICAR treatment potentiated endurance, but the combination of AICAR and GW0742 further potentiated endurance and increased all running parameters significantly relative to exercised and nonexercised groups (138-179% and 355% increase in running time, respectively).
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762202
03AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Efficacy outcome
In mice, AICAR with GW0742 increased running time by 355% versus the nonexercised group.
In plain wordsIn mice, AICAR with GW0742 increased running time by 355% compared with the nonexercised group.
Peptide
AICAR (acadesine)
Outcome
IncreaseCombination running time versus nonexercised group
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Comparator
Nonexercised group
Outcome group
Exercise and physical function · Musculoskeletal
Measurements
Running time increase
355%
versus nonexercised group
Source sentences
Summary
AICAR treatment potentiated endurance, but the combination of AICAR and GW0742 further potentiated endurance and increased all running parameters significantly relative to exercised and nonexercised groups (138-179% and 355% increase in running time, respectively).
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762203
04AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, basal whole-body metabolism did not change.
In plain wordsIn mice receiving AICAR and GW0742, resting whole-body metabolism did not change.
Peptide
AICAR (acadesine)
Outcome
No significant changeBasal whole-body metabolism
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Energy expenditure and thermogenesis · Metabolic and weight
Source sentences
Summary
Despite the lack of change in basal whole-body metabolism, a significant shift to fat as the main energy source with a decline in carbohydrate utilization was observed upon indirect calorimetry analysis at the period near exhaustion.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762204
05AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, fuel use shifted toward fat near exhaustion.
In plain wordsIn mice receiving AICAR and GW0742, fat became the main energy source near exhaustion.
Peptide
AICAR (acadesine)
Outcome
IncreaseFat utilization near exhaustion
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Energy expenditure and thermogenesis · Metabolic and weight
Source sentences
Summary
Despite the lack of change in basal whole-body metabolism, a significant shift to fat as the main energy source with a decline in carbohydrate utilization was observed upon indirect calorimetry analysis at the period near exhaustion.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762205
06AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, carbohydrate utilization declined near exhaustion.
In plain wordsIn mice receiving AICAR and GW0742, carbohydrate use decreased near exhaustion.
Peptide
AICAR (acadesine)
Outcome
DecreaseCarbohydrate utilization near exhaustion
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Energy expenditure and thermogenesis · Metabolic and weight
Source sentences
Summary
Despite the lack of change in basal whole-body metabolism, a significant shift to fat as the main energy source with a decline in carbohydrate utilization was observed upon indirect calorimetry analysis at the period near exhaustion.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762206
07AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, available energy substrates increased before exercise.
In plain wordsIn mice receiving AICAR and GW0742, energy substrates increased before exercise.
Peptide
AICAR (acadesine)
Outcome
IncreaseEnergy substrates before exercise
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Energy expenditure and thermogenesis · Metabolic and weight
Source sentences
Summary
Increased energy substrates before exercise, and elevated muscle nonesterified fatty acids (NEFA) and elevated muscle glycogen at exhaustion were observed together with increased PDK4 mRNA expression.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762207
08AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, muscle nonesterified fatty acids increased at exhaustion.
In plain wordsIn mice receiving AICAR and GW0742, muscle nonesterified fatty acids increased at exhaustion.
Peptide
AICAR (acadesine)
Outcome
IncreaseMuscle NEFA at exhaustion
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Lipids · Musculoskeletal
Source sentences
Summary
Increased energy substrates before exercise, and elevated muscle nonesterified fatty acids (NEFA) and elevated muscle glycogen at exhaustion were observed together with increased PDK4 mRNA expression.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762208
09AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, muscle glycogen increased at exhaustion.
In plain wordsIn mice receiving AICAR and GW0742, muscle glycogen increased at exhaustion.
Peptide
AICAR (acadesine)
Outcome
IncreaseMuscle glycogen at exhaustion
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Energy expenditure and thermogenesis · Musculoskeletal
Source sentences
Summary
Increased energy substrates before exercise, and elevated muscle nonesterified fatty acids (NEFA) and elevated muscle glycogen at exhaustion were observed together with increased PDK4 mRNA expression.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762209
10AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, PDK4 mRNA expression increased.
In plain wordsIn mice receiving AICAR and GW0742, PDK4 mRNA expression increased.
Peptide
AICAR (acadesine)
Outcome
IncreasePDK4 mRNA expression
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Receptor activity and mechanism · Musculoskeletal
Source sentences
Summary
Increased energy substrates before exercise, and elevated muscle nonesterified fatty acids (NEFA) and elevated muscle glycogen at exhaustion were observed together with increased PDK4 mRNA expression.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762210
11AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In mice, citrate synthase activity increased in AICAR-treated groups.
In plain wordsIn mice, citrate synthase activity increased in groups receiving AICAR.
Peptide
AICAR (acadesine)
Outcome
IncreaseCitrate synthase activity
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Mitochondrial function · Musculoskeletal
Source sentences
Summary
Citrate synthase activity was elevated in AICAR-treated groups, while PGC-1α protein level tended to be increased in GW0742-treated groups.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762211
12AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, muscle Pgc1a increased at exhaustion.
In plain wordsIn mice receiving AICAR and GW0742, muscle Pgc1a increased at exhaustion.
Peptide
AICAR (acadesine)
Outcome
IncreaseMuscle Pgc1a at exhaustion
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Receptor activity and mechanism · Musculoskeletal
Source sentences
Summary
At exhaustion, Pgc1a was robustly upregulated together with Pdk4, Cd36, and Lpl in the muscle.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762212
13AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, muscle Pdk4 increased at exhaustion.
In plain wordsIn mice receiving AICAR and GW0742, muscle Pdk4 increased at exhaustion.
Peptide
AICAR (acadesine)
Outcome
IncreaseMuscle Pdk4 at exhaustion
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Receptor activity and mechanism · Musculoskeletal
Source sentences
Summary
At exhaustion, Pgc1a was robustly upregulated together with Pdk4, Cd36, and Lpl in the muscle.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762213
14AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, muscle Cd36 increased at exhaustion.
In plain wordsIn mice receiving AICAR and GW0742, muscle Cd36 increased at exhaustion.
Peptide
AICAR (acadesine)
Outcome
IncreaseMuscle Cd36 at exhaustion
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Receptor activity and mechanism · Musculoskeletal
Source sentences
Summary
At exhaustion, Pgc1a was robustly upregulated together with Pdk4, Cd36, and Lpl in the muscle.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762214
15AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, muscle Lpl increased at exhaustion.
In plain wordsIn mice receiving AICAR and GW0742, muscle Lpl increased at exhaustion.
Peptide
AICAR (acadesine)
Outcome
IncreaseMuscle Lpl at exhaustion
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Receptor activity and mechanism · Musculoskeletal
Source sentences
Summary
At exhaustion, Pgc1a was robustly upregulated together with Pdk4, Cd36, and Lpl in the muscle.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762215
16AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, liver Pgc1a increased.
In plain wordsIn mice receiving AICAR and GW0742, liver Pgc1a increased.
Peptide
AICAR (acadesine)
Outcome
IncreaseLiver Pgc1a
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
A robust upregulation of Pgc1a and a downregulation in Chrebp were observed in the liver.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762216
17AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In trained mice receiving AICAR and GW0742, liver Chrebp decreased.
In plain wordsIn mice receiving AICAR and GW0742, liver Chrebp decreased.
Peptide
AICAR (acadesine)
Outcome
DecreaseLiver Chrebp
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
A robust upregulation of Pgc1a and a downregulation in Chrebp were observed in the liver.
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762217
18AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Efficacy outcome
In trained mice, combined AICAR and GW0742 further potentiated endurance compared with AICAR alone.
In plain wordsIn mice, AICAR with GW0742 increased endurance more than AICAR alone.
Peptide
AICAR (acadesine)
Outcome
IncreaseCombination endurance versus AICAR alone
Study
mousen: not reported in source
treadmill-trained Balb/c mice
Comparator
AICAR alone
Outcome group
Exercise and physical function · Musculoskeletal
Source sentences
Summary
AICAR treatment potentiated endurance, but the combination of AICAR and GW0742 further potentiated endurance and increased all running parameters significantly relative to exercised and nonexercised groups (138-179% and 355% increase in running time, respectively).
1 context sentence(design, population, supporting numbers)
Summary · context
Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2699762218

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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