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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.

Lithium bis͑fluorosulfonyl͒imide ͑LiFSI͒ has been investigated as a conducting salt of liquid electrolytes for lithium-ion batteries. It shows high solubility in most polar solvents, and a concentration of 5 M ͑mol dm −3 ͒ is reached in dimethyl carbonate ͑DMC͒ despite its low dielectric constant. LiFSI shows a thermal stability up to 180°C on the thermogravimetric test. Compared with the LiPF 6 /carbonate electrolytes, the LiFSI-based ones show higher ionic conductivities over a wide temperature range ͑−50 to 50°C͒ and higher lithium-ion transference numbers ͑t Li +͒ of 0.5-0.6. The conductivities of the LiFSI/DMC electrolyte over the 0.1-5 M concentration range obey a modified Casteel-Amis equation. The temperature dependence of 1 M LiFSI/DMC/EMC ͑3:7, v/v͒ is governed by the Vogel-Tammann-Fulcher relationship. The Fourier transform infrared spectra of the LiFSI/DMC electrolytes at different concentrations are systematically investigated. DMC shows significant spectral variations upon adding LiFSI, indicating strong interaction of Li + cations with the solvent molecules. We also found that the compatibility with graphite anode and LiFePO 4 cathode in the LiFSI-based electrolyte is as good as that in the LiPF 6 -based one, though aluminum ͑Al͒ corrosion occurs above 4 V vs Li + /Li. LiFSI is a very good contender to replace the latter, with increased performances and safety.

BackgroundRat liver regeneration (LR) proceeds along a process of highly organized and ordered tissue growth in response to the loss or injury of liver tissue, during which many physiological processes may play important roles. The molecular mechanism of hepatocyte proliferation, energy metabolism and substance metabolism during rat LR had been elucidated. Further, the correlation of circular RNA (circRNA) abundance with proliferation has recently been clarified. However, the regulatory capacity of circRNA in rat LR remains a fascinating topic.ResultsTo investigate the regulatory mechanism of circRNA during priming phase of rat LR, high-throughput RNA sequencing technology was performed to unbiasedly profile the expression of circRNA during priming phase of rat LR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis was conducted to predict the functions of differentially expressed circRNAs and their host linear transcripts. Co-expression networks of circRNA-miRNA were constructed based on the correlation analysis between the differentially expressed LR-related circRNAs and the condition of their miRNA binding sites. To excavate the key circRNAs in the early phase of rat LR, we comprehensively evaluated and integrated the relationship of expression level between the circRNAs and the linear transcripts as well as the distribution of miRNA binding sites in circRNA sequences.ConclusionsThis paper is the first to employ the comprehensive circRNA expression profile and to investigate circRNA-miRNA interactions during priming phase of rat LR. Two thousand four hundred twelve circRNAs were detected, and 159 circRNAs deriving from 116 host linear transcripts differentially expressed (p < 0.05). Six significantly changed circRNAs during priming phase of rat LR were screened as key circle molecules, and then were validated by qRT-PCR. This study will lay the foundation for revealing the functional roles of circRNAs during rat LR and help solve the remaining clinical problems.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3476-6) contains supplementary material, which is available to authorized users.

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