Project Grant R03AG102038

REPLICATION ANALYSIS TO IDENTIFY ACUTE MOLECULAR RESPONSES TO EXERCISE THAT LEAD TO CHRONIC TRAINING ADAPTATIONS - PROJECT SUMMARY/ABSTRACT THE MOLECULAR TRANSDUCERS OF PHYSICAL EXERCISE CONSORTIUM (MOTRPAC) IS TASKED WITH DEFINING THE MOLECULAR FOOTPRINT THAT UNDERLIES THE IMMENSELY BENEFICIAL EFFECTS OF EXERCISE ON HEALTH. THE ANIMAL COMPONENT OF MOTRPAC CONSISTS OF TWO MAJOR STUDIES: ONE INVESTIGATING EXERCISE TRAINING AND THE OTHER THE EFFECTS OF A SINGLE BOUT OF ACUTE EXERCISE. THESE STUDIES USE FISCHER 344 RATS AT 6 AND 18 MONTHS OF AGE TO DETERMINE THE MOLECULAR EFFECTS OF EXERCISE TRAINING AND ACUTE EXERCISE ACROSS 19 DIFFERENT TISSUES. SEVEN DIFFERENT OMICS PLATFORMS ARE BEING USED TO DETERMINE EXERCISE EFFECTS ON AN ENORMOUS NUMBER OF FACTORS, INCLUDING BUT NOT LIMITED TO GENES, PROTEINS, PHOSPHOPROTEINS, AND METABOLITES. FOR THIS R03 PROJECT, WE WILL USE THE ACUTE EXERCISE STUDY DATA IN CONJUNCTION WITH THE TRAINING STUDY DATA TO IDENTIFY THE KEY MOLECULAR CHANGES THAT OCCUR IN RESPONSE TO A SINGLE BOUT OF ACUTE EXERCISE THAT RESULTS IN CHRONIC TRAINING-INDUCED ADAPTATIONS. THIS IS A HIGHLY SIGNIFICANT QUESTION BECAUSE THE IDENTIFICATION AND VALIDATION OF THESE ACUTE MOLECULAR RESPONSES COULD PROVIDE NOVEL TARGETS TO ACTIVATE THE HEALTH PROMOTING EFFECTS OF EXERCISE. WHILE THERE HAS BEEN A LONG-STANDING HYPOTHESIS IN THE EXERCISE SCIENCE FIELD THAT CHRONIC TRAINING ADAPTATIONS RESULT FROM THE ACCUMULATION OF ACUTE MOLECULAR RESPONSES THAT OCCUR WITH EACH INDIVIDUAL EXERCISE BOUT, MOST OF THESE STUDIES FOCUSED ON SINGLE GENES OR PROTEINS AND MOST HAVE ONLY BEEN DONE IN SKELETAL MUSCLE. HERE, USING THE VAST MOTRPAC DATA SETS, WE WILL BE ABLE TO ANALYZE THE GLOBAL ACUTE EXERCISE MOLECULAR RESPONSES IN CONJUNCTION WITH TRAINING ADAPTATIONS IN AN UNPRECEDENTED MANNER. TO ACHIEVE THIS GOAL, WE PROPOSE TO USE A NOVEL AND INNOVATIVE REPLICATION METHOD WE HAVE DEVELOPED TO IDENTIFY MOLECULAR CHANGES THAT OCCUR WITH BOTH ACUTE EXERCISE AND TRAINING. GIVEN THE ENORMITY OF MOTRPAC DATA AND THE ONE-YEAR LENGTH OF THE R03 PROJECT, DATA FROM TWO TISSUES WILL BE STUDIED, SUBCUTANEOUS WHITE ADIPOSE TISSUE (SCWAT) AND KIDNEY. THESE TISSUES WERE CHOSEN DUE TO THEIR ROLE IN METABOLIC HEALTH AND BECAUSE THEY UNDERGO SIGNIFICANT MOLECULAR CHANGES IN RESPONSE TO EXERCISE. THE SPECIFIC AIMS ARE: 1) TO IDENTIFY MOLECULAR ADAPTATIONS THAT REPLICATE BETWEEN ACUTE EXERCISE AND EXERCISE TRAINING IN SCWAT AND KIDNEY; AND 2) TO IDENTIFY MOLECULAR ADAPTATIONS WITHIN TISSUES THAT REPLICATE BETWEEN TRANSCRIPTOMIC/PHOSPHOPROTEOMIC RESPONSES TO ACUTE EXERCISE AND PROTEOME CHANGES IN TRAINING. WE ANTICIPATE GENERATING A LARGE DATABASE OF THESE POTENTIAL HEALTH-PROMOTING MOLECULES THAT WILL BE AN IMPORTANT RESOURCE FOR THE SCIENTIFIC COMMUNITY. FOR OUR LAB, AS PART OF THIS PROJECT, WE WILL USE PATHWAY ANALYSIS COMBINED WITH OUR PHYSIOLOGICAL KNOWLEDGE TO SELECT 5-10 CANDIDATES FROM EACH OF THE GENE, PROTEIN, PHOSPHOPROTEIN, AND METABOLITE OMES. IN FUTURE STUDIES, CANDIDATES WILL UNDERGO AN IN-DEPTH INVESTIGATION OF MECHANISMS OF ACTION AND UTILITY AS A THERAPEUTIC TARGET. THUS, THE DATA FROM THIS R03 PROJECT WILL PROVIDE A FOUNDATION FOR DEVELOPING THERAPEUTIC TARGETS FOR CHRONIC DISEASES AND UNDERSTANDING THE FUNDAMENTAL MOLECULAR MECHANISMS OF EXERCISE-INDUCED IMPROVEMENTS IN HEALTH.