Hui Jiang1, Amirfarbod Yazdanyar1, Bin Lou1, Yunqin Chen1, Xiaomin Zhao1, Ruohan Li1, Hai Hoang Bui1, Ming-Shang Kuo1, Mohamad Navab1, Shucun Qin1, Zhiqiang Li1, Weijun Jin1, Xian-Cheng Jiang2. 1. From the Department of Cell Biology, State University of New York, Downstate Medical Center, Brooklyn (H.J., A.Y., Y.C., X.Z., R.L., Z.L., W.J., X.C.J.); Fudan University, Shanghai, China (B.L., Y.C.); Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System, New York (Z.L., X.C.J); Institute of Atherosclerosis, Taishan Medical University, Taian, China (X.Z., S.Q.); Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN (H.H.B., M.S.K.); and Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA (M.N.). 2. From the Department of Cell Biology, State University of New York, Downstate Medical Center, Brooklyn (H.J., A.Y., Y.C., X.Z., R.L., Z.L., W.J., X.C.J.); Fudan University, Shanghai, China (B.L., Y.C.); Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System, New York (Z.L., X.C.J); Institute of Atherosclerosis, Taishan Medical University, Taian, China (X.Z., S.Q.); Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN (H.H.B., M.S.K.); and Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA (M.N.). XJiang@downstate.edu.
Abstract
OBJECTIVE: Phospholipid transfer protein (PLTP) is highly expressed in adipose tissues. Thus, the effect of adipose tissue PLTP on plasma lipoprotein metabolism was examined. APPROACH AND RESULTS: We crossed PLTP-Flox-ΔNeo and adipocyte protein 2 (aP2)-Cre recombinase (Cre) transgenic mice to create PLTP-Flox-ΔNeo/aP2-Cre mice that have a 90 and a 60% reduction in PLTP mRNA in adipose tissue and macrophages, respectively. PLTP ablation resulted in a significant reduction in plasma PLTP activity (22%), high-density lipoprotein-cholesterol (21%), high-density lipoprotein-phospholipid (20%), and apolipoprotein A-I (33%) levels, but had no effect on nonhigh-density lipoprotein levels in comparison with those of PLTP-Flox-ΔNeo controls. To eliminate possible effects of PLTP ablation by macrophages, we lethally irradiated PLTP-Flox-ΔNeo/aP2-Cre mice and PLTP-Flox-ΔNeo mice, and then transplanted wild-type mouse bone marrow into them to create wild-type→PLTP-Flox-ΔNeo/aP2-Cre and wild-type→PLTP-Flox-ΔNeo mice. Thus, we constructed a mouse model (wild-type→PLTP-Flox-ΔNeo/aP2-Cre) with PLTP deficiency in adipocytes but not in macrophages. These knockout mice also showed significant decreases in plasma PLTP activity (19%) and cholesterol (18%), phospholipid (17%), and apolipoprotein A-I (26%) levels. To further investigate the mechanisms behind the reduction in plasma apolipoprotein A-I and high-density lipoprotein lipids, we measured apolipoprotein A-I-mediated cholesterol efflux in adipose tissue explants and found that endogenous and exogenous PLTP significantly increased cholesterol efflux from the explants. CONCLUSIONS: Adipocyte PLTP plays a small but significant role in plasma PLTP activity and promotes cholesterol efflux from adipose tissues.
OBJECTIVE:Phospholipid transfer protein (PLTP) is highly expressed in adipose tissues. Thus, the effect of adipose tissue PLTP on plasma lipoprotein metabolism was examined. APPROACH AND RESULTS: We crossed PLTP-Flox-ΔNeo and adipocyte protein 2 (aP2)-Cre recombinase (Cre) transgenic mice to create PLTP-Flox-ΔNeo/aP2-Cremice that have a 90 and a 60% reduction in PLTP mRNA in adipose tissue and macrophages, respectively. PLTP ablation resulted in a significant reduction in plasma PLTP activity (22%), high-density lipoprotein-cholesterol (21%), high-density lipoprotein-phospholipid (20%), and apolipoprotein A-I (33%) levels, but had no effect on nonhigh-density lipoprotein levels in comparison with those of PLTP-Flox-ΔNeo controls. To eliminate possible effects of PLTP ablation by macrophages, we lethally irradiated PLTP-Flox-ΔNeo/aP2-Cremice and PLTP-Flox-ΔNeo mice, and then transplanted wild-type mouse bone marrow into them to create wild-type→PLTP-Flox-ΔNeo/aP2-Cre and wild-type→PLTP-Flox-ΔNeo mice. Thus, we constructed a mouse model (wild-type→PLTP-Flox-ΔNeo/aP2-Cre) with PLTP deficiency in adipocytes but not in macrophages. These knockout mice also showed significant decreases in plasma PLTP activity (19%) and cholesterol (18%), phospholipid (17%), and apolipoprotein A-I (26%) levels. To further investigate the mechanisms behind the reduction in plasma apolipoprotein A-I and high-density lipoprotein lipids, we measured apolipoprotein A-I-mediated cholesterol efflux in adipose tissue explants and found that endogenous and exogenous PLTP significantly increased cholesterol efflux from the explants. CONCLUSIONS: Adipocyte PLTP plays a small but significant role in plasma PLTP activity and promotes cholesterol efflux from adipose tissues.
Authors: Niko L Setälä; Juha M Holopainen; Jari Metso; Susanne K Wiedmer; Gebrenegus Yohannes; Paavo K J Kinnunen; Christian Ehnholm; Matti Jauhiainen Journal: Biochemistry Date: 2007-02-06 Impact factor: 3.162
Authors: Anny Mulya; Ji-Young Lee; Abraham K Gebre; Elena Y Boudyguina; Soon-Kyu Chung; Thomas L Smith; Perry L Colvin; Xian-Cheng Jiang; John S Parks Journal: J Lipid Res Date: 2008-06-25 Impact factor: 5.922
Authors: Marian C Cheung; Gertrud Wolfbauer; Hiroshi Deguchi; José A Fernández; John H Griffin; John J Albers Journal: Biochim Biophys Acta Date: 2008-12-30
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