Circadian clocks in adipose tissue are known to regulate adipocyte biology. 
Although circadian dysregulation is associated with development of obesity, the 
underlying mechanism has not been established. Here we report that disruption of 
the clock gene, brain and muscle Arnt-like 1 (Bmal1), in mice led to increased 
adipogenesis, adipocyte hypertrophy, and obesity, compared to wild-type (WT) 
mice. This is due to its cell-autonomous effect, as Bmal1 deficiency in 
embryonic fibroblasts, as well as stable shRNA knockdown (KD) in 3T3-L1 
preadipocyte and C3H10T1/2 mesenchymal stem cells, promoted adipogenic 
differentiation. We demonstrate that attenuation of Bmal1 function resulted in 
down-regulation of genes in the canonical Wnt pathway, known to suppress 
adipogenesis. Promoters of these genes (Wnt10a, β-catenin, Dishevelled2, TCF3) 
displayed Bmal1 occupancy, indicating direct circadian regulation by Bmal1. As a 
result, Wnt signaling activity was attenuated by Bmal1 KD and augmented by its 
overexpression. Furthermore, stabilizing β-catenin through Wnt ligand or GSK-3β 
inhibition achieved partial restoration of blunted Wnt activity and suppression 
of increased adipogenesis induced by Bmal1 KD. Taken together, our study 
demonstrates that Bmal1 is a critical negative regulator of adipocyte 
development through transcriptional control of components of the canonical Wnt 
signaling cascade, and provides a mechanistic link between circadian disruption 
and obesity.