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Updated: May 1, 2026

Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Group 1B phospholipase A₂ inactivation suppresses atherosclerosis and metabolic diseases in LDL receptor-deficient
Norris I Hollie1, Eddy S Konaniah1, Colleen Goodin1
1Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
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.
Methods And 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.
Conclusion:
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.
Insights
Inactivating group 1B phospholipase A2 (Pla2g1b) prevents diet-induced obesity, diabetes, and atherosclerosis in mice. This suggests targeting Pla2g1b may reduce these conditions in humans.
Area of Science:
- Biochemistry
- Metabolic Diseases
- Cardiovascular Research
Background:
- Group 1B phospholipase A2 (Pla2g1b) inactivation is known to mitigate diet-induced metabolic dysfunction in C57BL/6 mice.
- The impact of Pla2g1b inactivation on atherosclerosis has not been previously investigated.
Purpose of the Study:
- To evaluate the efficacy of Pla2g1b inactivation in preventing atherosclerosis in a preclinical model.
- To assess the role of Pla2g1b in diet-induced obesity, hyperglycemia, and hyperlipidemia.
Main Methods:
- Utilized LDL receptor-deficient (Ldlr(-/-)) mice, exhibiting human-like hyperlipidemia.
- Administered a hypercaloric diet (58.5% fat, 25% sucrose) for 10 weeks.
- Compared atherosclerosis development and metabolic markers between Pla2g1b(+/+)Ldlr(-/-) and Pla2g1b(-/-)Ldlr(-/-) mice.
Main Results:
- Pla2g1b(-/-)Ldlr(-/-) mice were resistant to diet-induced body weight gain.
- These mice showed significantly lower fasting glucose, insulin, and plasma lipid levels.
- Atherosclerotic lesions in the aortic roots were reduced seven-fold in Pla2g1b(-/-)Ldlr(-/-) mice.
Conclusions:
- Pla2g1b inactivation effectively suppresses diet-induced obesity, diabetes, and atherosclerosis in Ldlr(-/-) mice.
- Pharmacological inhibition of Pla2g1b presents a potential therapeutic strategy for reducing obesity and associated risks in humans.
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