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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on June 30, 2006; DOI: 10.1124/jpet.106.104950

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Yaron Ilan
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*Compound via MeSH
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*Metabolic Syndrome


Received for publication March 24, 2006.
Revised June 29, 2006.
Accepted for publication June 29, 2006.

GLUCOCEREBROSIDE AMELIORATES THE METABOLIC SYNDROME IN OB/OB MICE

Maya Margalit 1, Zvi Shalev 2, Orit Pappo 2, Myriam Sklair-Levy 2, Ruslana Alper 2, Moshe Gomori 2, Dean Engelhardt 2, Rabbani Elazar 2, Yaron Ilan 2*

1 Hebrew University Hadassah Medical center 2 Hebrew University Hadassah Medical Center

* Address correspondence to: E-mail: ilan{at}hadassah.org.il

Abstract

Glucocerebroside (GC), a naturally occurring glycolipid, may alter 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 to controls. A significant decrease in liver size and hepatic fat content were observed in GC treated mice vs. controls. Near-normalization of glucose tolerance and decreased serum triglyceride levels were observed in GC treated mice. FACS analysis of peripheral and intrahepatic lymphocytes revealed a 1.6 fold increase of the peripheral/intrahepatic NKT lymphocyte ratio. A 33% decrease of the serum IFN{gamma} level and a 2.6 fold increase of the serum IL10 level were noted in GC-treated mice. Administration of GC led to significant amelioration of the metabolic alterations in leptin-deficient mice. The correlation with an altered lymphocyte subset profile suggests that this effect may have been immune-mediated. Immune modulation by GC may have a role in the treatment of NASH and other immune-mediated disorders.


Key words: Glucocerebroside, Metabolic syndrome, NKT lymphocytes, immune modulation, inflammation, regulatory cells


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[Abstract] [Full Text] [PDF]


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