Abstract
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-γ 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.
Footnotes
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This work was supported in part by grants from the Roaman-Epstein Liver Research Foundation and ENZO Biochem NY (to Y.I.)
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.104950.
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ABBREVIATIONS: NASH, nonalcoholic steatohepatitis; NKT, natural killer T; GC, glucocerebroside; IL, interleukin; PBS, phosphate-buffered saline; MRI, magnetic resonance imaging; BSA, bovine serum albumin; IFN-γ, interferon-γ; SI, signal intensity; TNF-α, tumor necrosis factor; MFI, MRI fatty liver index.
- Received March 24, 2006.
- Accepted June 29, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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