title: Altered expression and function of hepatic natural killer T cells in obese and diabetic KK-A(y)  mice.
abstract: OBJECTIVE
  To evaluate the role of natural killer (NK)T cells in the pathogenesis of non-alcoholic steatohepatitis (NASH), here we investigated the expression and function of hepatic NKT cells in KK-A(y)  mice, an animal model of metabolic syndrome.
  
  
  METHODS
  Male, 8-week-old KK-A(y)  and C57Bl/6 mice were fed a high-fat (HF) diet for 4 weeks. Some mice were given daily intragastric injections of pioglitazone for 5 days prior to or after dietary treatment.
  
  
  RESULTS
  In untreated KK-A(y)  mice, the percentages of NKT cells in liver mononucleolar cells were nearly one-third of those in C57Bl/6 controls. Elevations in interleukin (IL)-4 and interferon (IFN)-γ mRNA in the liver after a single injection of α-galactosylceramide (GalCer) were blunted in KK-A(y)  mice largely. Percentages of NKT cells, as well as GalCer-induced increases in IL-4 mRNA, were blunted significantly in both strains after HF diet feeding for 4 weeks. Interestingly, KK-A(y)  mice pretreated with pioglitazone showed significant increases in NKT cell proportion, and GalCer-induced increases in IL-4 and IFN-γ mRNA were also enhanced by pioglitazone. In KK-A(y)  mice, the percentages of annexin V positive NKT cells were nearly 2.5-fold higher than those in C57Bl/6 controls; however, pioglitazone decreased annexin V positive cells significantly. Moreover, pioglitazone increased NKT cell fraction in KK-A(y)  mice even after HF diet feeding.
  
  
  CONCLUSIONS
  KK-A(y)  mice exhibit proportional and functional alterations in hepatic NKT cells in close relation with the development of steatohepatitis, and it is postulated that pioglitazone improves steatohepatitis in part through restoration of hepatic NKT cells.
authors: Departments of Gastroenterology             Immunology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Hisafumi
authors: H
authors: Yamagata
authors: Kenichi
authors: K
authors: Ikejima
authors: Kazuyoshi
authors: K
authors: Takeda
authors: Tomonori
authors: T
authors: Aoyama
authors: Kazuyoshi
authors: K
authors: Kon
authors: Ko
authors: K
authors: Okumura
authors: Sumio
authors: S
authors: Watanabe