Expression profile of mRNAs encoding core circadian regulatory proteins in human subcutaneous adipose tissue: correlation with age and body mass index

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Abstract
Objective: Circadian mechanisms underlie the physiology of mammals as an adaptation to the earth's rotation on its axis. Highly conserved core circadian regulatory proteins (CCRPs) maintain an oscillatory expression profile in the central and peripheral tissues. The CCRP include both a positive and negative arm, as well as downstream transcriptional regulators. Recent studies in murine models have determined that the mRNAs encoding the CCRP are present in multiple adipose tissue depots and exhibit a robust oscillatory expression profile. This study set out to examine the expression of CCRP mRNAs in human subcutaneous adipose tissues. Design: Retrospective analysis of total RNA isolated from subcutaneous adipose tissue. Subjects: A total of 150 healthy female and male lean (body mass index (BMI) 30) subjects of varied ethnic backgrounds undergoing elective liposuction or surgical procedures. Results: The expression of the CCRP mRNAs displayed a significant correlation between each other and mRNAs representative of adipogenic biomarkers. Hierarchical cluster analyses of mRNAs isolated from the cohort of female Caucasian subjects (n=116) identified three major clusters based on expression of downstream CCRP mRNAs. The mRNAs encoding D site of albumin promoter-binding protein (DBP), E4 promoter-binding protein 4 (E4BP4), PPARγ coactivator-1β (PGC-1β) and Rev-erbα were negatively correlated with BMI in a lean cluster (n=66), positively correlated with BMI in a younger overweight/obese cluster (n=19), and not significantly correlated with BMI in an older, overweight/obese cluster (n=31). Conclusions: These data confirm and extend findings that link the CCRP and circadian mechanisms to the risk of obesity.