Endocrine Abstracts

There is a growing body of literature indicating that circadian mechanisms regulate metabolism in adipose tissues. Genes encoding the core circadian regulatory proteins (CCRP) display a robust oscillatory expression profile in murine adipose tissue depots, as well as the bone, liver, and heart. Temporally restricted food access as well as photic stimuli can entrain the CCRP expression. In murine models, deletion or mutation of the CCRP genes, clock and PPAR gamma coactivator 1 (PGC1), have been associated with increased risk of obesity and/or abnormal metabolic function. Transcriptomic analyses using classical algorithms demonstrate that >20% of the expressed genes in these tissues exhibit circadian rhythmicity. These in vivo findings have been extended to in vitro models. The expression profile of CCRP encoding genes can be synchronized in primary cultures of undifferentiated and adipocyte-differentiated human adipose-derived stem cells by dexamethasone. Similar observations relating to the synchronization of CCRP genes have been made in murine 3T3-L1 pre-adipoctyes. In addition, siRNA suppression of the CCRP Bmal1 inhibited adipogenesis in the 3T3-L1 model. A survey of human adipose tissue mRNAs has correlated the expression of the CCRP encoding genes with adipogenic markers. In light of epidemiological evidence linking circadian dysregulation to the incidence of obesity, hypertension, cardiac disease, and the metabolic syndrome, there is a need for further understanding of the relationship between chronobiology and adipose biology.