The potent growth promoter lysophosphatidic acid is reduced in plasma following the administration of the HDL mimetic peptide 4F (671.11)

Abstract

Introduction. Lysophosphatidic acid is a potent growth promoter that acts through high affinity G‐protein coupled receptors including the six receptors termed: LPA1 to LPA6. Because of its ability to stimulate cell proliferation, aberrant LPA‐signaling has been linked to cancer in numerous ways. Our group previously reported that feeding a high fat high cholesterol diet (Western diet) to ApoE deficient mice would increase the circulating levels of lysophosphatidic acid. HDL mimetic peptide 4F has been shown to have an extremely high affinity for lysophosphatidic acid and this might be used to lower the levels of this inflammatory molecule. Objective: We sought to determine if administering 4F to ApoE deficient mice on a Western diet would affect the levels of circulating lysophophosphatidic acid. Methods: Female ApoE deficient mice, 4 to 5 months of age (n=20 per group), were maintained on a Western diet for 8 weeks. One group also received 4F in drinking water at 100 ug per ml. Following 8 weeks, the mice were fasted overnight, blood was removed under anesthesia from the retro orbital sinus, and plasma was prepared and stored at ‐80°C. Lysophospholipid acid determination was done using solid phase extraction and LC‐ESI‐MS/MS, while isomers C20:4 and C18:2 were quantified. Results: Administration of 4F to the ApoE mice on a Western diet resulted in a significant reduction in the circulating levels of lysophospholipid C20:4 and C18:2 (p<0.01 for both). The level of lysophospholipid 18:0 did not show any detectable changes between the two groups. Conclusion: The data indicates that the HDL mimetic peptide 4F has the ability to reduce the Western diet induced increase in plasma levels of lysophospholipids involved in inflammatory reactions. This may be a useful consideration in helping reduce atherogenic or oncogenic conditions.