Dataset Information

Adipocyte phospholipid transfer protein and lipoprotein metabolism.

ABSTRACT: Phospholipid transfer protein (PLTP) is highly expressed in adipose tissues. Thus, the effect of adipose tissue PLTP on plasma lipoprotein metabolism was examined.We crossed PLTP-Flox-?Neo and adipocyte protein 2 (aP2)-Cre recombinase (Cre) transgenic mice to create PLTP-Flox-?Neo/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-?Neo controls. To eliminate possible effects of PLTP ablation by macrophages, we lethally irradiated PLTP-Flox-?Neo/aP2-Cre mice and PLTP-Flox-?Neo mice, and then transplanted wild-type mouse bone marrow into them to create wild-type?PLTP-Flox-?Neo/aP2-Cre and wild-type?PLTP-Flox-?Neo mice. Thus, we constructed a mouse model (wild-type?PLTP-Flox-?Neo/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.Adipocyte PLTP plays a small but significant role in plasma PLTP activity and promotes cholesterol efflux from adipose tissues.

SUBMITTER: Jiang H

PROVIDER: S-EPMC4304886 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adipocyte phospholipid transfer protein and lipoprotein metabolism.

Jiang Hui H Yazdanyar Amirfarbod A Lou Bin B Chen Yunqin Y Zhao Xiaomin X Li Ruohan R Hoang Bui Hai H Kuo Ming-Shang MS Navab Mohamad M Qin Shucun S Li Zhiqiang Z Jin Weijun W Jiang Xian-Cheng XC

Arteriosclerosis, thrombosis, and vascular biology 20141204 2

<h4>Objective</h4>Phospholipid transfer protein (PLTP) is highly expressed in adipose tissues. Thus, the effect of adipose tissue PLTP on plasma lipoprotein metabolism was examined.<h4>Approach and results</h4>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 P ...[more]

PMID: 25477345

Similar Datasets

Project description:It remains unclear whether plasma phospholipid transfer protein (PLTP) is involved in hyper-coagulation or hypo-coagulation. This study investigated the direct effect of PLTP on platelet aggregation and the underlying mechanism. Washed platelets from humans or mice and mouse platelet-rich plasma and human recombinant PLTP were isolated. PLTP is present in human platelets. We assessed adenosine diphosphate (ADP)-, collagen- and thrombin-induced platelet aggregation, phosphatidylserine externalization and photothrombosis-induced cerebral infarction in mice. PLTP over-expression increased platelet aggregation, while PLTP deficiency had the opposing reaction. Human recombinant PLTP increased both mouse and human platelet aggregation in a dose-dependent manner. Phosphatidylserine externalization provides a water/lipid surface for the interaction of coagulation factors, which accelerates thrombosis. Compared with wild-type controls, platelets from PLTP transgenic mice had significantly more phosphatidylserine on the exterior surface of the plasma membrane, whereas platelets from PLTP-deficient mice had significantly less phosphatidylserine on the surface, thus PLTP influences fibrinogen binding on the plasma membrane. Moreover, recombinant PLTP together with ADP significantly increased phosphatidylserine exposure on the plasma membrane of PLTP-deficient platelets, thereby increasing fibrinogen binding. PLTP over-expression significantly accelerated the incidence of photothrombosis-induced infarction in mice, whereas PLTP deficiency significantly reduced the frequency of infarction. We concluded that PLTP promotes phosphatidylserine externalization at the plasma membrane of platelets and accelerates ADP- or collagen-induced platelet aggregation. This effect plays an important role in the initiation of thrombin generation and platelet aggregation under sheer stress conditions. Thus, PLTP is involved in hyper-coagulation. Therefore, PLTP inhibition could be a novel approach for countering thrombosis.

Dataset Information

Adipocyte phospholipid transfer protein and lipoprotein metabolism.

Publications

Adipocyte phospholipid transfer protein and lipoprotein metabolism.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets