CLOCK is involved in obesity-induced disordered fibrinolysis in ob/ob mice by regulating PAI-1 gene expression

Oishi, Katsutaka; Ohkura, Naoki; Wakabayashi, Miyuki; Shirai, Hidenori; Sato, Kosuke; Matsuda, Juzo; Atsumi, Gen‐ichi; Ishida, Norio

doi:10.1111/j.1538-7836.2006.02032.x

Cited by 79 publications

(58 citation statements)

References 43 publications

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“…For example, Clock mutant mice are obese and hyperphagic (107), although this phenotype may be modified by genetic background (110). Moreover, introgression of the Clock mutation into the ob/ob strain exacerbates obesity (111). In addition to causing metabolic disorders, both Clock mutant and Npas2 -/-mice display abnormalities in sleep architecture, so it will be critical to determine the cause-and-effect relationship between alterations in sleep and feeding in these models (112,113).…”

Section: Role Of the Circadian System In Energy Balance Metabolism mentioning

confidence: 99%

Circadian rhythms, sleep, and metabolism

Huang

Ramsey

Marcheva³

et al. 2011

J. Clin. Invest.

584

415

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The discovery of the genetic basis for circadian rhythms has expanded our knowledge of the temporal organization of behavior and physiology. The observations that the circadian gene network is present in most living organisms from eubacteria to humans, that most cells and tissues express autonomous clocks, and that disruption of clock genes results in metabolic dysregulation have revealed interactions between metabolism and circadian rhythms at neural, molecular, and cellular levels. A major challenge remains in understanding the interplay between brain and peripheral clocks and in determining how these interactions promote energy homeostasis across the sleep-wake cycle. In this Review, we evaluate how investigation of molecular timing may create new opportunities to understand and develop therapies for obesity and diabetes.

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Section: Role Of the Circadian System In Energy Balance Metabolism mentioning

confidence: 99%

Circadian rhythms, sleep, and metabolism

Huang

Ramsey

Marcheva³

et al. 2011

J. Clin. Invest.

584

415

View full text Add to dashboard Cite

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“…Recently, Oishi et al reported that Clock-mutant mice carrying ICR exhibited less obesity (12), while Clock-mutant mice carrying C57BL / 6J exhibited more obesity with the ob mutation (13). This paper also suggests the different effect of Clock mutation on obesity.…”

Section: Effect Of Clock Mutation On Lipid Metabolismmentioning

confidence: 55%

Circadian Rhythms in the CNS and Peripheral Clock Disorders: The Circadian Clock and Hyperlipidemia

2007

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Abstract. A circadian clock controls various physiological and behavioral rhythms. In mammals, a master circadian clock exists in the suprachiasmatic nucleus of the hypothalamus, and slave oscillators can be found in most tissues. These circadian oscillations are controlled by "clock genes". The negative feedback loop is thought to function as a molecular mechanism of the circadian clock. It is plausible that clock genes may control lipid metabolism through so-called clock-controlled genes and that lipid metabolism-related clock-controlled genes may play important roles in the circadian change of lipid metabolism. Recently research has focused on the relationships between the clock system and lipid metabolism. In this review, we discuss the following items: 1) circadian clock system, 2) effect of the diet on clock gene expression, 3) effect of clock mutation on lipid metabolism, and 4) effect of streptozotocin-induced diabetes and ob mutation on clock gene expression and lipid metabolism. In this review we have summarized how the circadian clock affects lipid metabolism through the expression of lipid metabolism-related clock-controlled genes and at the same time discussed how abnormal metabolism of lipid affects the expression of clock genes. Further experiments are needed to elucidate the detailed mechanism of interaction between clock genes and lipid metabolisms.

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“…Indeed, CLOCK protein is a positive regulator of PAI-1 mRNA expression (Oishi et al, 2006. That is, CLOCK/BMAL heterodimers transactivate the PAI-1 gene via the E-box element(s), and this activation is periodically suppressed by PER and CRY proteins.…”

Section: Discussionmentioning

confidence: 99%

“…The results of microarray analyses using hepatic RNA isolated from bezafibrate-treated wild-type Clock mutant and PPAR␣-null mice revealed that 136 genes were transcriptionally regulated by PPAR␣ in a CLOCK-dependent manner in the mouse liver. Among them, PAI-1 was typical of genes with expression that exhibits circadian variation and has both PPRE and an E-box element in the promoter region (Chen et al, 2006;Oishi et al, 2006). We thus further focused on this gene to investigate the transcriptional interaction between PPAR␣ and CLOCK.…”

Section: Discussionmentioning

confidence: 99%

Bezafibrate Induces Plasminogen Activator Inhibitor-1 Gene Expression in a CLOCK-Dependent Circadian Manner

Oishi

Koyanagi²,

Matsumoto³

et al. 2010

Mol Pharmacol

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A functional interaction between peroxisome proliferator-activated receptor ␣ (PPAR␣) and components of the circadian clock has been suggested, but whether these transcriptional factors interact to regulate the expression of their target genes remains obscure. Here we used a PPAR␣ ligand, bezafibrate, to search for PPAR␣-regulated genes that are expressed in a CLOCK-dependent circadian manner. Microarray analyses using hepatic RNA isolated from bezafibrate treated-wild type, Clock mutant (Clk/Clk), and PPAR␣-null mice revealed that 136 genes are transcriptionally regulated by PPAR␣ in a CLOCKdependent manner. Among them, we focused on the plasminogen activator inhibitor-1 (PAI-1) gene, because its expression typically shows circadian variation, and it has transcriptional response elements for both PPAR and CLOCK. The bezafibrate-induced expression of PAI-1 mRNA was attenuated in Clk/Clk mice and in PPAR␣-null mice. The protein levels of PPAR␣ were reduced in Clk/Clk hepatocytes. However, the overexpression of PPAR␣ could not rescue bezafibrate-induced PAI-1 expression in Clk/Clk hepatocytes, suggesting that impaired bezafibrate-induced PAI-1 expression in Clk/Clk mice is not due to reduced PPAR␣ expression. Luciferase reporter and chromatin immunoprecipitation analyses using primary hepatocytes demonstrated that DNA binding of both PPAR␣ and CLOCK is essential for bezafibrate-induced PAI-1 gene expression. Pull-down assays in vitro showed that both PPAR␣ and its heterodimerized partner retinoic acid receptor-␣ can serve as potential interaction targets of CLOCK. The present findings revealed that molecular interaction between the circadian clock and the lipid metabolism regulator affects the bezafibrate-induced gene expression.

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CLOCK is involved in obesity-induced disordered fibrinolysis in ob/ob mice by regulating PAI-1 gene expression

Cited by 79 publications

References 43 publications

Circadian rhythms, sleep, and metabolism

Circadian rhythms, sleep, and metabolism

Circadian Rhythms in the CNS and Peripheral Clock Disorders: The Circadian Clock and Hyperlipidemia

Bezafibrate Induces Plasminogen Activator Inhibitor-1 Gene Expression in a CLOCK-Dependent Circadian Manner

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