Hepatic Lipase mRNA, Protein, and Plasma Enzyme Activity Is Increased in the Insulin-Resistant, Fructose-Fed Syrian Golden Hamster and Is Partially Normalized by the Insulin Sensitizer Rosiglitazone

  1. Gary F. Lewis1,
  2. Susan Murdoch2,
  3. Kristine Uffelman1,
  4. Mark Naples3,
  5. Linda Szeto1,
  6. Alegria Albers2,
  7. Khosrow Adeli3 and
  8. John D. Brunzell2
  1. 1Department of Medicine and Physiology, Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada
  2. 2Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington
  3. 3Department of Laboratory Medicine and Pathobiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  1. Address correspondence and reprint requests to Gary F. Lewis, Toronto General Hospital, 200 Elizabeth St., EN11-229, Toronto, Ontario, Canada M5G 2C4. E-mail: gary.lewis{at}uhn.on.ca


Postheparin plasma hepatic lipase (HL) activity has been shown to correlate with features of the metabolic syndrome and type 2 diabetes in humans. We examined HL postheparin plasma enzyme activity, hepatocyte mRNA, and protein mass in the insulin-resistant, fructose-fed Syrian golden hamster, and the response of the insulin-sensitizing peroxisome proliferator–activated receptor-γ agonist rosiglitazone. Male Syrian golden hamsters were treated for 5 weeks with 1) normal diet (DIET group), 2) 60% fructose diet (FRUC group), or 3) 60% fructose and rosiglitazone (20 mmol · kg−1 · day−1) (FRUC+RSG group). Hepatocyte HL mRNA, protein mass, and postheparin plasma HL activity were increased in FRUC compared with DIET hamsters. FRUC+RSG hamsters had partial normalization of HL mRNA, mass, and activity. There was a shift in the size of LDL particles from large to small in FRUC animals and a shift back to large LDL size in FRUC+RSG. This is the first demonstration that HL hepatocyte mRNA, mass, and plasma enzymatic activity increase concomitantly with induction of an insulin-resistant state and can be partially normalized by treatment with an insulin sensitizer. The increase in HL in insulin-resistant states may play an important role in the typical dyslipidemia of these conditions, and reduction of HL could explain some of the beneficial effects of insulin sensitizers on the plasma lipid profile.


    • Accepted August 11, 2004.
    • Received May 11, 2004.
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