title: Oral Administration of β-Glucosylceramide for the Treatment of Insulin Resistance and Nonalcoholic Steatohepatitis: Results of a Double-Blind, Placebo-Controlled Trial.
abstract: β-glucosylceramide (GC) is a naturally occurring glycosphingolipid that was shown to improve hepatic steatosis, steatohepatitis, and insulin resistance in animal models of nonalcoholic fatty liver disease. In this study, we evaluated the safety and efficacy of oral administration of GC in subjects with nonalcoholic steatohepatitis (NASH). Twenty-three patients with biopsy proven NASH were enrolled in a double-blind, placebo-controlled trial. Patients were orally administered daily with 7.5 mg of GC. Patients were followed for safety, liver enzymes, HbA1c, insulin sensitivity, lipid profile, hepatic fat content as measured by magnetic resonance imaging (MRI), and NASH score on liver biopsy. No treatment-related adverse events were observed during treatment. In a per protocol analysis of data, oral administration of GC decreased the hepatic fat content as measured by MRI in GC-treated compared with placebo. HbA1C decreased in patients treated with GC. GC treatment was associated with a milder decrease in the high-density lipoprotein serum levels. The beneficial effects were associated with a decrease in CD4 and NKT cell subsets of lymphocytes. Due to the small number of subjects enrolled, differences did reach statistical significance. Oral administration of GC is safe and biologically active in patients with NASH and insulin resistance.
authors.affiliation: 1 Gasroeterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center , Jerusalem, Israel .
authors.forename: Gadi
authors.initials: G
authors.lastname: Lalazar
authors.affiliation: 1 Gasroeterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center , Jerusalem, Israel .
authors.forename: Ehud
authors.initials: E
authors.lastname: Zigmond
authors.affiliation: 2 Diabetes Unit, Department of Medicine, Hebrew University-Hadassah Medical Center , Jerusalem, Israel .
authors.forename: Sarah
authors.initials: S
authors.lastname: Weksler-Zangen
authors.affiliation: 1 Gasroeterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center , Jerusalem, Israel .
authors.forename: Ami Ben
authors.initials: AB
authors.lastname: Ya'acov
authors.affiliation: 3 Department of Radiology, Hebrew University-Hadassah Medical Center , Jerusalem, Israel .
authors.forename: Miriam Sklair
authors.initials: MS
authors.lastname: Levy
authors.affiliation: 1 Gasroeterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center , Jerusalem, Israel .
authors.forename: Nilla
authors.initials: N
authors.lastname: Hemed
authors.affiliation: 2 Diabetes Unit, Department of Medicine, Hebrew University-Hadassah Medical Center , Jerusalem, Israel .
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
authors.affiliation: 1 Gasroeterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center , Jerusalem, Israel .
authors.forename: Yaron
authors.initials: Y
authors.lastname: Ilan
mesh_terms: D000284:Administration, Oral; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005963:Glucosylceramides / Q000008:administration & dosage*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism; D055815:Young Adult
chemical_list: D005963:Glucosylceramides; D006442:Glycated Hemoglobin; D007328:Insulin; D008075:Lipoproteins, HDL; C517652:hemoglobin A1c protein, human
keywords: NASH; NKT cells; diabetes; insulin resistance; β-glucosylceramide