The role of Nocturnin in adipogenesis, obesity and metabolic disorders
Date Issued
2011
Date
2011
Author(s)
Hee, Siow-Wey
Abstract
The deadenylase nocturnin (Noc, Ccrn4l) has been recently found to regulate lipid metabolism and to control preadipocyte differentiation. Here we showed that among the five deadenylases tested; only Noc exhibited a biphasic expression during adipocyte differentiation, while the expression levels of other deadenylases, including Pan2, Parn, Ccr4, and Caf1 were relatively unchanged or reduced during adipogenesis. The immediate early-expressed Noc during 3T3-L1 adipogenesis was involved in regulating mitotic clonal expansion and cyclin D1 expression, as demonstrated in Noc-silenced 3T3-L1 cells and Noc-/- primary mouse embryonic fibroblasts (MEFs). Transcriptional profiling of Noc¬-depleted 3T3-L1 adipocytes revealed that most of the differentially expressed genes were related to cell growth and proliferation. An mRNA destabilizer, tristetraprolin (TTP), was further identified as an interacting partner of Noc during early adipogenesis. Screening of TTP mRNA targets in adipose tissue of Noc-/- mice revealed that the Polo-like kinase 3 (Plk3) mRNA expression was significantly upregulated. Ectopic expression of Noc further decreases Plk3 expression in 3T3-L1 preadipocytes.
In human adipose tissue, NOC mRNA level negatively associated with both fasting serum insulin and HOMA-IR, and positively associated with both adiponectin mRNA levels and circulating adiponectin levels. Moreover, NOC mRNA levels were also positively correlated with TTP mRNA levels in human adipose tissues. We further found that PLK3 mRNA levels were not associated with BMI, but were significant higher in subcutaneous adipose tissues (SAT) comparing to visceral adipose tissues (VAT). Furthermore, PLK3 mRNA levels in both VAT and SAT were strongly positively correlated with adiponectin gene expression as well as serum concentrations. The SAT PLK3 mRNA expressions were negatively correlated with fasting insulin levels and HOMA-IR even after adjustment of age, sex and BMI. Taken together, these results suggest the role of Noc in the modulation of early adipogenesis as well as systemic insulin sensitivity. Our findings also suggest that PLK3 is associated with systemic insulin sensitivity.
Subjects
circadian rhythm
adipocyte
insulin resistance
metabolic syndrome
SDGs
Type
thesis
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