title: Group 1B phospholipase A₂ inactivation suppresses atherosclerosis and metabolic diseases in LDL receptor-deficient mice.
abstract: OBJECTIVE
  Previous studies have shown that inactivation of the group 1B phospholipase A2 (Pla2g1b) suppresses diet-induced obesity, hyperglycemia, insulin resistance, and hyperlipidemia in C57BL/6 mice. A possible influence of Pla2g1b inactivation on atherosclerosis has not been addressed previously. The current study utilized LDL receptor-deficient (Ldlr(-/-)) mice with plasma lipid levels and distribution similar to hyperlipidemic human subjects as a preclinical animal model to test the effectiveness of Pla2g1b inactivation on atherosclerosis.
  
  
  RESULTS
  The Pla2g1b(+/+)Ldlr(-/-) and Pla2g1b(-/-)Ldlr(-/-) mice were fed a low fat chow diet or a hypercaloric diet with 58.5 kcal% fat and 25 kcal% sucrose for 10 weeks. Minimal differences were observed between Pla2g1b(+/+)Ldlr(-/-) and Pla2g1b(-/-)Ldlr(-/-) mice when the animals were maintained on the low fat chow diet. However, when the animals were maintained on the hypercaloric diet, the Pla2g1(+/+)Ldlr(-/-) mice showed the expected body weight gain but the Pla2g1b(-/-)Ldlr(-/-) mice were resistant to diet-induced body weight gain. The Pla2g1b(-/-)Ldlr(-/-) mice also displayed lower fasting glucose, insulin, and plasma lipid levels compared to the Pla2g1b(+/+)Ldlr(-/-) mice, which displayed robust hyperglycemia, hyperinsulinemia, and hyperlipidemia in response to the hypercaloric diet. Importantly, atherosclerotic lesions in the aortic roots were also reduced 7-fold in the Pla2g1b(-/-)Ldlr(-/-) mice.
  
  
  CONCLUSIONS
  The effectiveness of Pla2g1b inactivation to suppress diet-induced body weight gain and reduce diabetes and atherosclerosis in LDL receptor-deficient mice suggests that pharmacological inhibition of Pla2g1b may be a viable strategy to decrease diet-induced obesity and the risk of diabetes and atherosclerosis in humans.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
authors.forename: Norris I
authors.initials: NI
authors.lastname: Hollie
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
authors.forename: Eddy S
authors.initials: ES
authors.lastname: Konaniah
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Goodin
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA. Electronic address: huidy@ucmail.uc.edu.
authors.forename: David Y
authors.initials: DY
authors.lastname: Hui
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D004041:Dietary Fats; D004195:Disease Models, Animal; D002149:Energy Intake; D054500:Group IB Phospholipases A2 / Q000172:deficiency* / Q000235:genetics; D006943:Hyperglycemia / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D006946:Hyperinsulinism / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D006949:Hyperlipidemias / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D015430:Weight Gain
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D008055:Lipids; D011973:Receptors, LDL; D054500:Group IB Phospholipases A2; C516203:Pla2g1b protein, mouse
keywords: Atherosclerosis; Glucose tolerance; Lipid and lipoprotein metabolism; Phospholipase
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