کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5946740 | 1172361 | 2014 | 4 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Group 1B phospholipase A2 inactivation suppresses atherosclerosis and metabolic diseases in LDL receptor-deficient mice Group 1B phospholipase A2 inactivation suppresses atherosclerosis and metabolic diseases in LDL receptor-deficient mice](/preview/png/5946740.png)
- Inactivation of the group 1B phospholipase A2 ameliorates diet-induced atherosclerosis.
- Group 1B phospholipase A2 inactivation improves insulin sensitivity.
- Group 1B phospholipase A2 inactivation suppresses diet-induced body weight gain.
ObjectivePrevious 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 (Ldlrâ/â) 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 resultsThe Pla2g1b+/+Ldlrâ/â and Pla2g1bâ/âLdlrâ/â 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+/+Ldlrâ/â and Pla2g1bâ/âLdlrâ/â mice when the animals were maintained on the low fat chow diet. However, when the animals were maintained on the hypercaloric diet, the Pla2g1+/+Ldlrâ/â mice showed the expected body weight gain but the Pla2g1bâ/âLdlrâ/â mice were resistant to diet-induced body weight gain. The Pla2g1bâ/âLdlrâ/â mice also displayed lower fasting glucose, insulin, and plasma lipid levels compared to the Pla2g1b+/+Ldlrâ/â 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 Pla2g1bâ/âLdlrâ/â mice.ConclusionThe 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.
Journal: Atherosclerosis - Volume 234, Issue 2, June 2014, Pages 377-380