Circulating Oligomeric State and Circadian Rhythm Regulation of CTRP3
Location
White Top Mtn
Start Date
4-12-2019 9:00 AM
End Date
4-12-2019 2:30 PM
Poster Number
119
Faculty Sponsor’s Department
Health Sciences
Name of Project's Faculty Sponsor
Dr. Jonathan Peterson
Type
Poster: Competitive
Project's Category
Circadian Rhythms, Metabolic Syndrome, Diabetes
Abstract or Artist's Statement
Adipose tissue secretes many important biologically active proteins called adipokines. A subset of adipokines, called C1q tumor necrosis factor (TNF) related proteins (CTRPs), play a key role in metabolism, inflammation, and cell signaling. C1q TNF Related Protein 3 (CTRP3) increases hepatic fatty acid oxidation, decreases inflammation, and aids in cardiovascular recovery following a myocardial infarction. However, the mechanisms behind CTRP3’s protective effects on organ systems are unknown. This exploratory study aims to analyze the circulating oligomeric state of CTRP3 and the circadian regulation of CTRP3 to help understand the role of CTRP3 in preventing disease. METHODS: For analysis of the oligomeric state of CTRP3 non-fasting mouse serum was collected from high fat fed hyper-glycemic mice or low fat fed normoglycemic mice and was separated by size exclusion filtration. For analysis of the circadian regulation of CTRP3 serum samples were collected from mice at 4 different time points (2 dark cycle and 2 light cycle) throughout the day and circulating CTRP3 levels were analyzed by immunoblot analysis. RESULTS: In both high fat and low fat fed mice CTRP3 was found to circulate in both >300 kDa oligomers and >100kDa oligomers, with no detectable amount of CTRP3 less 100 kDa. Interestingly, although there was no difference in the total amount of CTRP3 between the high fat and low fat fed mice there was a higher abundance of CTRP3 >300 kDa in the high fat fed and a greater abundance of CTRP3 found 100-300 kDa. Additionally, we found that serum CTRP3 levels vary greatly throughout a 24-hour time-period within each mouse, but no consensus circadian pattern was observed. CONCLUSION: In vitro mammalian produced recombinant CTRP3 protein was found to exist as trimer, hexamer, and high molecule weight. This is the first study to indicate that CTRP3 circulates in different oligomeric states in vivo, and this is also the first study to observe a difference in the oligomeric state of CTRP3 related to metabolic state. Combined these findings indicate that oligomeric state of CTRP3 may be more metabolically relevant than total amount of circulating CTRP3. In addition, our finding of a high variability of CTRP3 within the same mouse at different times throughout the day indicates that is not regulated by circadian rhythms but is susceptible to variability due to some unknown regulatory factor. These findings have identified novel unknown aspects of CTRP3, which require further research to understand the role of CTRP3 in human health and disease.
Circulating Oligomeric State and Circadian Rhythm Regulation of CTRP3
White Top Mtn
Adipose tissue secretes many important biologically active proteins called adipokines. A subset of adipokines, called C1q tumor necrosis factor (TNF) related proteins (CTRPs), play a key role in metabolism, inflammation, and cell signaling. C1q TNF Related Protein 3 (CTRP3) increases hepatic fatty acid oxidation, decreases inflammation, and aids in cardiovascular recovery following a myocardial infarction. However, the mechanisms behind CTRP3’s protective effects on organ systems are unknown. This exploratory study aims to analyze the circulating oligomeric state of CTRP3 and the circadian regulation of CTRP3 to help understand the role of CTRP3 in preventing disease. METHODS: For analysis of the oligomeric state of CTRP3 non-fasting mouse serum was collected from high fat fed hyper-glycemic mice or low fat fed normoglycemic mice and was separated by size exclusion filtration. For analysis of the circadian regulation of CTRP3 serum samples were collected from mice at 4 different time points (2 dark cycle and 2 light cycle) throughout the day and circulating CTRP3 levels were analyzed by immunoblot analysis. RESULTS: In both high fat and low fat fed mice CTRP3 was found to circulate in both >300 kDa oligomers and >100kDa oligomers, with no detectable amount of CTRP3 less 100 kDa. Interestingly, although there was no difference in the total amount of CTRP3 between the high fat and low fat fed mice there was a higher abundance of CTRP3 >300 kDa in the high fat fed and a greater abundance of CTRP3 found 100-300 kDa. Additionally, we found that serum CTRP3 levels vary greatly throughout a 24-hour time-period within each mouse, but no consensus circadian pattern was observed. CONCLUSION: In vitro mammalian produced recombinant CTRP3 protein was found to exist as trimer, hexamer, and high molecule weight. This is the first study to indicate that CTRP3 circulates in different oligomeric states in vivo, and this is also the first study to observe a difference in the oligomeric state of CTRP3 related to metabolic state. Combined these findings indicate that oligomeric state of CTRP3 may be more metabolically relevant than total amount of circulating CTRP3. In addition, our finding of a high variability of CTRP3 within the same mouse at different times throughout the day indicates that is not regulated by circadian rhythms but is susceptible to variability due to some unknown regulatory factor. These findings have identified novel unknown aspects of CTRP3, which require further research to understand the role of CTRP3 in human health and disease.