Abstract 18977: High Fat Diet Enriched With Saturated Fat Increases Lipopolysaccharide-Induced Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice
Background: It is known that lipopolysaccharide (LPS) induces atherosclerosis in animal models, underscoring an important role of inflammation in atherosclerosis. Our recent in vitro studies showed that saturated fatty acid (SFA) had a synergy with LPS on upregulation of inflammatory cytokines.
Hypothesis: We hypothesized that high-fat diet (HFD) enriched with saturated fat (SF) increases LPS-induced atherosclerosis.
Methods: Low-density lipoprotein receptor-deficient (LDLR-/-) mice were fed low-fat diet (LFD, 13% calories from fat), HFD with low SF (HFD-LS, 60% calories from fat, 37% fat was SF) or HFD with high SF (HFD-HS, 60% calories from fat, 93% fat was SF) for 20 weeks. During the last 12 weeks, half mice received intraperitoneal injection of LPS (25 microgram/mouse, once a week) while the other half received PBS. After treatments, metabolic parameters and aortic atherosclerosis of all mice (n=6-9) were analyzed.
Results: Results showed that either HFD-LS or HFD-HS significantly increased bodyweight as compared LFD. HFD-LS, but not HFD-HS, increased glucose as compared to LFD. Both HFD-LS and HFD-HS increased serum cholesterol to a similar level, but only HFD-HS increased triglycerides as compared to LFD. Results also showed that LPS did not change bodyweight, glucose, cholesterol and triglycerides significantly. Furthermore, quantification of en face Sudan IV-stained atherosclerotic lesions in aortas showed that treatment with LPS, HFD-LS or HFD-HS alone significantly increased atherosclerosis (p=0.001, 0.022, 0.001, respectively) and HFD-HS induced more lesions than HFD-LS (p=0.041). Interestingly, HFD-HS significantly increased LPS-induced atherosclerosis (p=0.028), but HFD-LS did not (p=0.481). To understand the mechanisms, we determined the effect of SFA on LPS-induced cytokines and lipid metabolic genes in macrophages. Results showed that palmitic acid, a most abundant SFA in human body, increased LPS-induced expression of inflammatory cytokines and acyl-CoA cholesterol acyltransferase 2.
Conclusions: This study showed that HFD-HS, but not HFD-LS, increases LPS-induced atherosclerosis in LDLR-/- mice and the synergy between SFA and LPS on pro-atherosclerotic genes may play a role in the increased atherosclerosis.
Author Disclosures: Z. Lu: None. Y. Li: None. C. Brinson: None. M. Lopes-Virella: None. Y. Huang: None.
- © 2016 by American Heart Association, Inc.