Characterization of Peripheral Circadian Clocks in Adipose Tissues

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Abstract
First described in the suprachiasmatic nucleus, circadian clocks have since been found in several peripheral tissues. Although obesity has been associated with dysregulated circadian expression profiles of leptin, adiponectin, and other fat-derived cytokines, there have been no comprehensive analyses of the circadian clock machinery in adipose depots. In this study, we show robust and coordinated expression of circadian oscillator genes (Npas2, Bmal1, Per1-3, and Cry1-2) and clock-controlled downstream genes (Rev-erbα, Rev-erbβ, Dbp, E4bp4, Stra13, and Id2) in murine brown, inguinal, and epididymal (BAT, iWAT, and eWAT) adipose tissues. These results correlated with respective gene expression in liver and the serum markers of circadian function. Through Affymetrix microarray analysis, we identified 650 genes that shared circadian expression profiles in BAT, iWAT, and liver. Furthermore, we have demonstrated that temporally restricted feeding causes a coordinated phase-shift in circadian expression of the major oscillator genes and their downstream targets in adipose tissues. The presence of circadian oscillator genes in fat has significant metabolic implications, and their characterization may have potential therapeutic relevance with respect to the pathogenesis and treatment of diseases such as obesity, type 2 diabetes, and the metabolic syndrome.