| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
We have previously reported that cyclic stretching preferentially reduces the expression of PPARγ_2 during the induction period through prolonged activation of extracellular-signal-regulated protein kinase (ERK). This lead to the inhibition of the commitment of adipocyte differentiation (1). This inhibitory effect of the stretching was significantly augmented when the cells were concomitantly treated with EPA, a fish-oil-derived ω-3 polyunsaturated fatty acid (PUFA), but not with DHA, another PUFA having a closely related structure of EPA (2). The differential effects of the EPA and DHA were possibly due to a difference in the substrate specificities of COX-2 for PUFAs, an inducible cyclooxygenase isozyme, and we found that the stretching significantly augmented the expression of COX-2, and that a selective COX-2 inhibitor (NS-398) inhibited the combined effect of the stretching and EPA (2). Adipogenesis could be affected positively or negatively by prostaglandins (PG), thus significan
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ce of mechanical stimuli during commitment stage of adipocyte differentiation might be considered to be augmentation of COX-2-dependent PG-production as well as downregulation of PPARγ_2. We also examined the effect of local vibration in conscious mice twice in a day (100 Hz for 30 min), targeting on lower abdomen of a mouse just above the left epididymal fat for up to 16 days. After that, the expressions of PPARγ_2 and SREBP-Ic transcripts and the amount of intracellular triglyceride have been lowered, whereas transcripts for COX-2 and proinflammatory cytokines, such as IL-6 and IL-1β, were increased in the epididymal fat tissues of mice. It has been shown that IL-β not only inactivates PPARγ but also induces expression of COX-2. However, no apparent synergistic effect was observed when the cells were concomitantly treated with IL-1β and EPA during the commitment stage of adipocyte differentiation. This suggested that mechanical stress-induced COX-2 plays a different role as compared with the inflammation-induced COX-2. It can be concluded that a part of the mechanism of adipocyte responses against mechanical stresses became clear, and the mechanical stresses may increase the efficacy of pharmacological interventions in adiposity through the synergistic interaction of certain drugs affecting adipocyte functions. (1) Tanabe Y, et. al., J. Cell Sci. 117, 3605-3614, 2004 ; (2) Tanabe Y, et. al., J. Pharmacol. Sci. 106, 478-484, 2008. Less
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