Endocrine Abstracts

Circadian mechanisms regulate metabolism in adipose tissues. The genes encoding the circadian regulatory proteins oscillate over a 24 h period in human and murine adipose tissue depots,. This expression profile is entrained by photic stimuli, temporally restricted food access, and/or nuclear hormone receptor ligands, such as glucocorticoids. In mice, deletion or mutation of the circadian regulatory genes, clock and PPAR gamma coactivator 1 (PGC1), is associated with increased risk of obesity and/or abnormal glucose metabolic function. Bioinformatic analyses of transcriptomic data indicate that >20% of the adipose-tissue expressed genes exhibit pronounced circadian or diurnal rhythmicity. These in vivo findings can be observed in in vitro models. For example, dexamethasone exposure synchronizes the expression profile of circadian protein encoding genes in primary cultures of undifferentiated and adipocyte-differentiated human adipose-derived stem cells. Similar observations regarding the synchronization of circadian regulatory genes have been reported in murine 3T3-L1 pre-adipocyte cultures. In addition, multiple circadian regulators directly modulate both adipogenic and osteogenic differentiation in these in vitro models. The expression profiles of the circadian regulatory genes correlate directly with those of adipogenic markers in human adipose tissue mRNAs. Furthermore, polymorphisms in circadian regulatory genes have been correlated directly with obesity risk in human subjects. There is a growing body of endocrine and epidemiological evidence linking circadian dysregulation to the incidence of obesity, hypertension, cardiac disease, and the metabolic syndrome. Consequently, there will be a potential role for targeting circadian mechanisms in the treatment of clinical endocrine and metabolic disorders of adipose tissue using behavioral and/or pharmacological interventions.

Declaration of interest: The author declares that there is a conflict of interest.

Funding: This work was supported, however funding details are unavailable.