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INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Glucocerebroside Ameliorates the Metabolic Syndrome in OB/OB Mice

Liver Unit Department of Medicine (M.M., Z.S., R.A., Y.I.), Department of Pathology (O.P.), Department of Radiology (M.S.-L., M.G.), Hadassah Hebrew University Medical Center, Jerusalem, Israel; and ENZO Biochem, New York (D.E., E.R.)

Glucocerebroside (GC) is a naturally occurring glycolipid that may alter natural killer T (NKT) cell function. To determine the effect of GC on the metabolic derangements and immune profile in leptin-deficient mice, Ob/Ob mice were treated by daily injections of GC for 8 weeks and followed for various metabolic and immunological parameters. Marked amelioration of the metabolic alterations characteristic of leptin-deficient mice was observed in GC-treated animals compared with controls. A significant decrease in liver size and hepatic fat content were observed in GC-treated mice. Near-normalization of glucose tolerance and decreased serum triglyceride levels were observed. Fluorescence-activated cell sorting analysis of peripheral and intrahepatic lymphocytes revealed a 1.6-fold increase of the peripheral/intrahepatic NKT lymphocyte ratio. A 33% decrease of serum interferon- level and a 2.6-fold increase of serum interleukin 10 level were noted in GC-treated mice. Immune modulation by GC may have a role in the treatment of nonalcoholic steatohepatitis and other immune-mediated disorders.

Address correspondence to: Dr. Yaron Ilan, M.D., Liver Unit, Department of Medicine, Hebrew University-Hadassah Medical Center, P.O.B 12000, Jerusalem, Israel IL-91120. E-mail: ilan{at}hadassah.org.il

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