Yamada Yoko, Eto Masato, Ito Yuki, Mochizuki Satoru, Son Bo-Kyung, Ogawa Sumito, Iijima Katsuya, Kaneki Masao, Kozaki Koichi, Toba Kenji, Akishita Masahiro, Ouchi Yasuyoshi
Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2015 Aug 28;10(8):e0136597. doi: 10.1371/journal.pone.0136597. eCollection 2015.
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.
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.
eNOS-/- mice induce NASH development, and these findings provide new insights into the therapeutic approach for fatty liver disease and related disorders.
代谢综合征会导致胰岛素抵抗，并与危险因素聚集相关，从而增加动脉粥样硬化的风险。最近，有报道称内皮型一氧化氮合酶缺陷（eNOS-/-）小鼠表现出代谢紊乱。有趣的是，也有报道称eNOS在包括脂肪细胞在内的非内皮细胞中表达，但其在脂肪细胞中的功能仍不清楚。
随着脂肪细胞分化，eNOS表达被诱导，抑制eNOS/NO可在体外和体内增强脂肪分解。此外，给予高脂饮食（HFD）能够在eNOS-/-小鼠中诱导非酒精性脂肪性肝炎（NASH），但在野生型小鼠中则不会。PPARγ拮抗剂可增加脂肪细胞中eNOS的表达，并抑制HFD诱导的肝脏脂肪变化。
eNOS-/-小鼠会引发NASH的发展，这些发现为脂肪肝疾病及相关病症的治疗方法提供了新的见解。
