Lack of myeloid Fatp1 increases atherosclerotic lesion size in Ldlr-/- mice.
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ABSTRACT: BACKGROUND AND AIMS:Altered metabolism is an important regulator of macrophage (M?) phenotype, which contributes to inflammatory diseases such as atherosclerosis. Broadly, pro-inflammatory, classically-activated M?s (CAM) are glycolytic while alternatively-activated M?s (AAM) oxidize fatty acids, although overlap exists. We previously demonstrated that M? fatty acid transport protein 1 (FATP1, Slc27a1) was necessary to maintain the oxidative and anti-inflammatory AAM phenotype in vivo in a model of diet-induced obesity. The aim of this study was to examine how M? metabolic reprogramming through FATP1 ablation affects the process of atherogenesis. We hypothesized that FATP1 limits M?-mediated inflammation during atherogenesis. Thus, mice lacking M? Fatp1 would display elevated formation of atherosclerotic lesions in a mouse model lacking the low-density lipoprotein (LDL) receptor (Ldlr-/-). METHODS:We transplanted bone marrow collected from Fatp1+/+ or Fatp1-/- mice into Ldlr-/- mice and fed chimeric mice a Western diet for 12 weeks. Body weight, blood glucose, and plasma lipids were measured. Aortic sinus and aorta lesions were quantified. Atherosclerotic plaque composition, oxidative stress, and inflammation were analyzed histologically. RESULTS:Compared to Fatp1+/+Ldlr-/- mice, Fatp1-/-Ldlr-/- mice exhibited significantly larger lesion area and elevated oxidative stress and inflammation in the atherosclerotic plaque. Macrophage and smooth muscle cell content did not differ by Fatp1 genotype. There were no significant systemic alterations in LDL, high-density lipoprotein (HDL), total cholesterol, or triacylglyceride, suggesting that the effect was local to the cells of the vessel microenvironment in a Fatp1-dependent manner. CONCLUSIONS:M? Fatp1 limits atherogenesis and may be a viable target to metabolically reprogram M?s.
SUBMITTER: Zhao L
PROVIDER: S-EPMC5705203 | biostudies-literature | 2017 Nov
REPOSITORIES: biostudies-literature
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