title: Suppressive Role of PPARγ-Regulated Endothelial Nitric Oxide Synthase in Adipocyte Lipolysis.
abstract: BACKGROUND
  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.
  
  
  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.
authors: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Yoko
authors: Y
authors: Yamada
authors: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Masato
authors: M
authors: Eto
authors: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Yuki
authors: Y
authors: Ito
authors: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Satoru
authors: S
authors: Mochizuki
authors: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Bo-Kyung
authors: BK
authors: Son
authors: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Sumito
authors: S
authors: Ogawa
authors: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Katsuya
authors: K
authors: Iijima
authors: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Masao
authors: M
authors: Kaneki
authors: Department of Geriatric Medicine, Kyorin University School of Medicine, Tokyo, Japan.
authors: Koichi
authors: K
authors: Kozaki
authors: Department of Geriatric Medicine, Kyorin University School of Medicine, Tokyo, Japan.
authors: Kenji
authors: K
authors: Toba
authors: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Masahiro
authors: M
authors: Akishita
authors: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Yasuyoshi
authors: Y
authors: Ouchi
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008066:Lipolysis; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis* / Q000235:genetics; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D047495:PPAR gamma; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse