4 years ago

Cooperative stimulation of atherogenesis by lipopolysaccharide and palmitic acid-rich high fat diet in low-density lipoprotein receptor-deficient mice

Either lipopolysaccharide (LPS) or high-fat diet (HFD) enriched with saturated fatty acid (SFA) promotes atherosclerosis. In this study, we investigated the effect of LPS in combination with SFA-rich HFD on atherosclerosis and how LPS and SFA interact to stimulate inflammatory response in vascular endothelial cells. Methods Low-density lipoprotein receptor-deficient (LDLR /) mice were fed low-fat diet (LFD), HFD with low palmitic acid (PA) (LP-HFD), or HFD with high PA (HP-HFD) for 20 weeks. During the last 12 weeks, half mice received LPS and half received PBS. After treatment, metabolic parameters and aortic atherosclerosis were analyzed. To understand the underlying mechanisms, human aortic endothelial cells (HAECs) were treated with LPS and/or PA and proinflammatory molecule expression was quantified. Results Metabolic study showed that LPS had no significant effect on cholesterol, triglycerides, free fatty acids, but increased insulin and insulin resistance. Both LP-HFD and HP-HFD increased body weight and cholesterol while LP-HFD increased glucose and HP-HFD increased triglycerides, insulin, and insulin resistance. Analysis of aortic atherosclerosis showed that HP-HFD was more effective than LP-HFD in inducing atherosclerosis and LPS in combination with HP-HFD increased atherosclerosis in the thoracic aorta, a less common site for atherosclerosis, as compared with LPS or HP-HFD. To understand the mechanisms, results showed that LPS and PA synergistically upregulated adhesion molecules and proinflammatory cytokines in HAECs. Conclusions LPS and PA-rich HFD cooperatively increased atherogenesis in the thoracic aorta. The synergy between LPS and PA on proinflammatory molecules in HAECs may play an important role in atherogenesis.

Publisher URL: www.sciencedirect.com/science

DOI: S0021915017312790

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