Yamada, YokoEto, MasatoIto, YukiMochizuki, SatoruSon, Bo-KyungOgawa, SumitoIijima, KatsuyaKaneki, MasaoKozaki, KoichiToba, KenjiAkishita, MasahiroOuchi, Yasuyoshi2015-10-012015Yamada, Y., M. Eto, Y. Ito, S. Mochizuki, B. Son, S. Ogawa, K. Iijima, et al. 2015. “Suppressive Role of PPARγ-Regulated Endothelial Nitric Oxide Synthase in Adipocyte Lipolysis.” PLoS ONE 10 (8): e0136597. doi:10.1371/journal.pone.0136597. http://dx.doi.org/10.1371/journal.pone.0136597.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:22857010Introduction: Metabolic syndrome causes insulin resistance and is associated with risk factor clustering, thereby increasing the risk of atherosclerosis. Recently, endothelial nitric oxide synthase deficient (eNOS-/-) mice have been reported to show metabolic disorders. Interestingly, eNOS has also been reported to be expressed in non-endothelial cells including adipocytes, but the functions of eNOS in adipocytes remain unclear. Methods and Results: The eNOS expression was induced with adipocyte differentiation and inhibition of eNOS/NO enhanced lipolysis in vitro and in vivo. Furthermore, the administration of a high fat diet (HFD) was able to induce non-alcoholic steatohepatitis (NASH) in eNOS-/- mice but not in wild type mice. A PPARγ antagonist increased eNOS expression in adipocytes and suppressed HFD-induced fatty liver changes. Conclusions: eNOS-/- mice induce NASH development, and these findings provide new insights into the therapeutic approach for fatty liver disease and related disorders.en-USJournal Article2015-10-0110.1371/journal.pone.0136597