The Deficiency Of Adipose ABC-transporter A1 Effects On Atherosclerosis

ATP binding cassette transporter A1(ABCA1)is a membrance-associated protein,mediates the cholesterol efflux to lipid-free/poor apo AI.Loss-function mutations of ABCA1 lead to Tangier disease with no HDL and massive foam cells in peripheral organs.Adipose ABCA1 is involved in the biogenesis of HDL.However,the impact of adipose ABCA1 on the formation of foam cells and atherosclerotic lesions is still unknown.Aims: To investigate the role of adipose ABCA1 in the development of foam cells and atherosclerosis.Methods: Fabp4 Cre recombinase transgenic mice were crossed with ABCA1flox/flox mice to generate adipocyte-specific Abca1 knockout(ABCA1ad-/ad-)mice.The deficiency of ABCA1 in adipose was validated by PCR and Q-PCR.Male and female ABCA1ad-/ad-mice and their counterparts(ABCA1+/+)on the LDLr-/-background were given the Western-type diet(WTD)for 9 weeks to induce the formation of early and advanced lesions.The body and fat weight,lipid content and gene expression of adipose tissue,plasma lipids levels,foam cell formation,and atherosclerotic lesion development were analyzed.Results: On regular chow diet,despite no changes in the amount of visceral fat and body weight,the deletion of ABCA1 increased the cholesterol and triglyceride(TG)stores in adipose tissue.The alteration of adipose lipids in ABCA1ad-/ad-mice did not influence the plasma levels of total cholesterol(TC),TG,glucose,and non-esterified fatty acids(NEFA).Of note,plasma levels of HDL-C are significantly lower in ABCA1ad-/ad-mice(0.90-fold,p<0.05),illustrating the importance of adipose ABCA1 in HDL biogenesis.When fed WTD,the adipose cholesterol and TG contents of ABCA1ad-/ad-mice was still higher,but the differences between two groups are significantly reduced.With comparable plasma lipids and glucose levels,ABCA1ad-/admice showed massive foam cell formation containing increased cholesterol ester in the peritoneal cavity,liver,and spleen.This massive ectopic foam cell formation was associated with the reduced early and advanced lesion formation in ABCA1ad-/ad-mice.Conclusion: Adipocyte ABCA1 is a key regulator of foam cell formation,and ectopic foam cell formation in spleens induced by the deletion of adipose ABCA1 could alleviate the development of atherosclerosis.