FGF21 protects against ox-LDL induced apoptosis through suppressing CHOP expression in THP1 macrophage derived foam cells.

En Li,Jin-Ying Zhang,Shao-Hui Niu,Tao Wang,Feng Wang,Ting Wang,Li-Qiang Sun,Li Li

doi:10.1186/s12872-015-0077-2

Abstract

BackgroundFGF21,as a member of the fibroblast growth factor superfamily, is an important endogenous regulator to systemic glucose and lipid metabolism. Elevated serum FGF21 levels have been reported in subjects with coronary heart disease and carotid artery plaques. The formation and apoptosis of foam cell, induced by ox-LDL and oxysterols, are key steps in the development of atherosclerosis.MethodsIn this study, THP1 derived macrophages were induced into foam cells by ox-LDL or sterols. The formation and apoptosis of foam cells treated with or without FGF21 were analyzed.ResultsWe demonstrated that the accumulation of cholesterol was decreased after FGF21 treatment in THP1 macrophage derived foam cells. Consistently, the apoptosis of macrophage was alleviated dramatically with FGF21 treatment. ERK1/2 knockdown didn’t abrogate the effect of FGF21 on THP1 macrophage derived foam cells. However, FGF21 suppressed the induced expression of CHOP and DR5 in THP1 macrophage derived foam cells.ConclusionFGF21 protects against the formation and apoptosis of THP1 macrophages derived foam cells through suppressing the expression of CHOP.

Highlights

FGF21,as a member of the fibroblast growth factor superfamily, is an important endogenous regulator to systemic glucose and lipid metabolism
FGF21 decreases the formation of foam cell fromTHP1 derived macrophages With the development of atherosclerosis, the infiltrated macrophages engulf low density lipoprotein (LDL) leading to the accumulation of cholesterol in the droplets, and the formation of foam cells
FGF21 protects against ox-LDL and 7-KC induced macrophage apoptosis The apoptosis of foam cells duo to over-loaded cholesterol is the key event during the development of atherosclerosis

Summary

Introduction

FGF21,as a member of the fibroblast growth factor superfamily, is an important endogenous regulator to systemic glucose and lipid metabolism. Among members of the FGF superfamily, FGF21 plays a very important regulatory role in glucose and lipid homeostasis [1,2,3]. FGF21 deficient mice showed mild weight gain, slightly impaired glucose homeostasis, and developed hepatosteatosis and obvious impairments in ketogenesis and glucose control when raised on a ketogenic diet [7]. These findings suggest that FGF21 is an important metabolic hormone in maintaining

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Conclusion