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Björn Dahlbäck
In Cell Reports, Christoffersen et al. [1] demonstrate that sphingosine 1-phosphate (S1P) bound to apolipoprotein M (apoM) regulates the activity and mass of brown adipose tissue (BAT). They found mice lacking apoM to have hyperactive BAT with high triglyceride (TG) utilization, resulting in low white adipose tissue (WAT) mass and low body weight.
March 13, 2018: Trends in Endocrinology and Metabolism: TEM
Bíborka Nádró, Lilla Juhász, Anita Szentpéteri, Dénes Páll, György Paragh, Mariann Harangi
Previous studies showed that plasma levels of high-density lipoprotein (HDL) cholesterol are inversely related to risk of cardiovascular diseases. However, in the last few decades it became obvious that beyond its plasma level, HDL structure and function have a critical role in its anti-atherogenic efficacy. Apolipoprotein M (ApoM) is an HDL-associated plasma protein affecting HDL metabolism and exhibits various anti-atherosclerotic functions, such as protection against oxidation and regulation of cholesterol efflux...
February 2018: Orvosi Hetilap
Ryo Terao, Megumi Honjo, Makoto Aihara
Sphingosine 1-phosphate (S1P) is a potent lipid mediator that modulates inflammatory responses and proangiogenic factors. It has been suggested that S1P upregulates choroidal neovascularization (CNV) and may be deeply involved in the pathogenesis of exudative age-related macular degeneration (AMD). Recent studies have suggested that apolipoprotein M (ApoM), a carrier protein for S1P, modulates the biological properties of S1P in the pathogenesis of atherosclerosis. However, the role of ApoM/S1P in AMD has not been explored...
December 31, 2017: International Journal of Molecular Sciences
Christina Christoffersen, Christine K Federspiel, Anna Borup, Pernille M Christensen, Andreas N Madsen, Markus Heine, Carsten H Nielsen, Andreas Kjaer, Birgitte Holst, Joerg Heeren, Lars B Nielsen
Apolipoprotein M (apoM) is the carrier of sphingosine-1-phosphate (S1P) in plasma high-density lipoproteins. S1P is a bioactive lipid interacting with five receptors (S1P1-5). We show that lack of apoM in mice increases the amount of brown adipose tissue (BAT), accelerates the clearance of postprandial triglycerides, and protects against diet-induced obesity (i.e., a phenotype similar to that induced by cold exposure or β3-adrenergic stimulation). Moreover, the data suggest that the phenotype of apoM-deficient mice is S1P dependent and reflects diminished S1P1 stimulation...
January 2, 2018: Cell Reports
Xiao Zhang, Puhong Zhang, Jialin Gao, Qiang Huang
Autophagy is thought to be a key mechanism in maintaining the balance of liver lipid metabolism. However, the relationship between apolipoprotein M (ApoM) and autophagy has not been reported, and the role of ApoM in triglyceride metabolism is still unclear. In this study, we investigated the correlation between ApoM and autophagy and liver triglyceride metabolism in ApoM-knockout animal and cellular models. First, we observed that spontaneous hepatic steatosis developed in the liver of adult ApoM-/- mice, which was presented as the accumulation of large quantities of lipid droplets in hepatocytes under electron microscopy; Oil Red O staining showed significant accumulation of triglycerides...
December 27, 2017: Biochemical and Biophysical Research Communications
Bin Zhu, Guang-Hua Luo, Yue-Hua Feng, Miao-Mei Yu, Jun Zhang, Jiang Wei, Chun Yang, Ning Xu, Xiao-Ying Zhang
It had been demonstrated that apolipoprotein M (apoM) is an important carrier of sphingosine-1-phosphate (S1P) in blood, and the S1P has critical roles in the pathogenesis of sepsis-induced acute lung injury (ALI). In the present study, we investigated whether apoM has beneficial effects in a mouse model after lipopolysaccharide (LPS)-induced ALI. Forty-eight mice were divided into two groups: male C57BL/6 wild-type (apoM+/+) group (n = 24) and apoM gene-deficient (apoM-/-) group (n = 24) and then randomly subdivided into four subgroups (n = 6 each) according to different intraperitoneal (i...
December 19, 2017: Inflammation
Huihui Mao, Guanghua Luo, Jun Zhang, Ning Xu
The base-quenched probe method for detecting single nucleotide polymorphisms (SNPs) relies on real-time PCR and melting-curve approaches. Here, we applied the most common commercial fluorophores including FAM, HEX, CY5, CY3, TET, JOE, Texas Red and ROX for labeling probes to detect multi-mutations simultaneously according to the different fluorescence channels. Accuracy of the method was confirmed by direct sequencing. The results demonstrated that all above dyes could be influenced by bases and could be applied to detect SNPs...
February 15, 2018: Analytical Biochemistry
Jonas W Brinck, Aurélien Thomas, Marie-Claude Brulhart-Meynet, Estelle Lauer, Cecilia Frej, Björn Dahlbäck, Peter Stenvinkel, Richard W James, Miguel A Frias
BACKGROUND: Chronic kidney disease (CKD) exacerbates the risk of death due to cardiovascular disease (CVD). Modifications to blood lipid metabolism which manifest as increases in circulating triglycerides and reductions in high-density lipoprotein (HDL) cholesterol are thought to contribute to increased risk. In CKD patients, higher HDL cholesterol levels were not associated with reduced mortality risk. Recent research has revealed numerous mechanisms by which HDL could favourably influence CVD risk...
February 2018: European Journal of Clinical Investigation
Puhong Zhang, Jialin Gao, Chun Pu, Yao Zhang
Dyslipidaemia in type 2 diabetes mellitus (T2DM) is characterized by high plasma triglyceride concentrations, reduced high‑density lipoprotein concentrations and increased small density low‑density lipoprotein concentrations. Dyslipidaemia may lead to cardiovascular disease (CVD) and other complications. Apolipoproteins mainly comprise six species, apolipoprotein (apo)A, apoB, apoC, apoD, apoE and apoM, which are important components of plasma lipoproteins that carry lipids and stabilize the structure of lipoproteins...
December 2017: Molecular Medicine Reports
Mikaël Croyal, Stéphanie Billon-Crossouard, Sophie Goulitquer, Audrey Aguesse, Luis León, Fanta Fall, Maud Chétiveaux, Thomas Moyon, Valentin Blanchard, Khadija Ouguerram, Gilles Lambert, Estelle Nobécourt, Michel Krempf
OBJECTIVE: ApoM (apolipoprotein M) binds primarily to high-density lipoprotein before to be exchanged with apoB (apolipoprotein B)-containing lipoproteins. Low-density lipoprotein (LDL) receptor-mediated clearance of apoB-containing particles could influence plasma apoM kinetics and decrease its antiatherogenic properties. In humans, we aimed to describe the interaction of apoM kinetics with other components of lipid metabolism to better define its potential benefit on atherosclerosis...
November 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Pernille M Christensen, Markus H Bosteen, Stefan Hajny, Lars B Nielsen, Christina Christoffersen
Sphingosine-1-phosphate (S1P) is a bioactive lipid implicated in e.g. angiogenesis, lymphocyte trafficking, and endothelial barrier function. Erythrocytes are a main source of plasma S1P together with platelets and endothelial cells. Apolipoprotein M (apoM) in HDL carries 70% of plasma S1P, whereas 30% is carried by albumin. The current aim was to investigate the role of apoM in export of S1P from human erythrocytes. Erythrocytes exported S1P more efficiently to HDL than to albumin, particularly when apoM was present in HDL...
November 8, 2017: Scientific Reports
Miao-Mei Yu, Shuang Yao, Kai-Ming Luo, Qin-Feng Mu, Yang Yu, Guang-Hua Luo, Ning Xu
Apolipoprotein M (ApoM) and the vitamin D receptor (VDR) are apolipoproteins predominantly presenting in high-density lipoprotein (HDL) and a karyophilic protein belonging to the steroid‑thyroid receptor superfamily, respectively. Previous studies have demonstrated that ApoM and VDR are associated with cholesterol metabolism, immune and colorectal cancer regulation. In order to investigate whether ApoM affected the expression of VDR in colorectal cancer cells, a single‑tube duplex fluorescence reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) system was developed to simultaneously detect the mRNA levels of VDR and GAPDH in HT‑29 cells overexpressing ApoM...
August 2017: Molecular Medicine Reports
Yang Yu, Jun Zhang, Yingying Qiao, Lili Pan, Juzhang Li, Huihui Mao, Jiang Wei, Xiaoying Zhang, Ning Xu, Guanghua Luo
BACKGROUND: It has been reported increased serum apoM levels seen in the patients suffered from obstructive sleep apnoea and chronic obstructive pulmonary diseases. In the present, we further examine the prevalence of apoM gene SNPs in COPD patients. And a new method base-quenched probe technique is established. METHODS: In the present study, we first used the Roche 454 GS Junior high-throughput sequencer to analyze 6 COPD samples and 6 control samples, in these samples we found 3 interesting SNPs (rs805264, rs707922 and rs707921) and then we designed primers and probes to establish a simple and quick screening method that is a base-quench probe technique and the genotype was confirmed by melting curves...
December 30, 2017: Gene
Abrar Ahmad, Kristina Sundquist, Bengt Zöller, Björn Dahlbäck, Johan Elf, Peter J Svensson, Karin Strandberg, Jan Sundquist, Ashfaque A Memon
Recently, decreased levels of apolipoprotein M (ApoM) were shown to be associated with higher risk of recurrent venous thromboembolism (VTE) in male patients. However, the role of ApoM in primary VTE is unknown. We aimed in our study to analyze the plasma levels of ApoM in patients with VTE in order to evaluate the diagnostic importance of ApoM in primary VTE. A total of 357 patients with suspected first episode of VTE were recruited prospectively in the SCORE study. Plasma samples from 307 patients were available for quantifying the plasma levels of ApoM in patients with VTE using sandwich enzyme-linked immunosorbent assay method...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
Lagu He, Pengfei Wu, Li Tan, Bai Le, Wenhan Du, Ting Shen, Jiali Wu, Zheyi Xiang, Min Hu
BACKGROUND: Apolipoprotein M (apoM) is a 26-kD apolipoprotein that is mainly expressed in specific cell types, such as human liver parenchymal cells and kidney proximal renal tubular epithelial cells. ApoM can regulate the formation of pre-β-HDL and the reverse cholesterol transport and thus plays an important role in the metabolism of lipids and lipoproteins, meaning that it can affect the development of lipid metabolism disorders. Significantly elevated serum apoM levels are detected in patients with hyperlipidemia...
September 6, 2017: Lipids in Health and Disease
Markus Høybye Bosteen, Eva Martha Madsen Svarrer, Line Stattau Bisgaard, Torben Martinussen, Marie Madsen, Lars Bo Nielsen, Christina Christoffersen, Tanja Xenia Pedersen
BACKGROUND AND AIMS: Chronic kidney disease is characterized by uremia and causes premature death, partly due to accelerated atherosclerosis. Apolipoprotein (apo) M is a plasma carrier protein for the lipid sphingosine-1-phosphate (S1P). The Apom-S1P complex associates with HDL, and may contribute to its anti-atherosclerotic effects. The role of Apom/S1P in atherosclerosis is presently controversial and has not been explored in a uremic setting. We aimed to explore whether plasma concentrations of Apom/S1P are altered by uremia and whether Apom overexpression or deficiency affects classical and uremic atherosclerosis...
August 18, 2017: Atherosclerosis
Steven L Swendeman, Yuquan Xiong, Anna Cantalupo, Hui Yuan, Nathalie Burg, Yu Hisano, Andreane Cartier, Catherine H Liu, Eric Engelbrecht, Victoria Blaho, Yi Zhang, Keisuke Yanagida, Sylvain Galvani, Hideru Obinata, Jane E Salmon, Teresa Sanchez, Annarita Di Lorenzo, Timothy Hla
Endothelial dysfunction, a hallmark of vascular disease, is restored by plasma high-density lipoprotein (HDL). However, a generalized increase in HDL abundance is not beneficial, suggesting that specific HDL species mediate protective effects. Apolipoprotein M-containing HDL (ApoM(+)HDL), which carries the bioactive lipid sphingosine 1-phosphate (S1P), promotes endothelial function by activating G protein-coupled S1P receptors. Moreover, HDL-bound S1P is limiting in several inflammatory, metabolic, and vascular diseases...
August 15, 2017: Science Signaling
Stefan Hajny, Christina Christoffersen
Hepatocytes, renal proximal tubule cells as well as the highly specialized endothelium of the blood brain barrier (BBB) express and secrete apolipoprotein M (apoM). ApoM is a typical lipocalin containing a hydrophobic binding pocket predominantly carrying Sphingosine-1-Phosphate (S1P). The small signaling molecule S1P is associated with several physiological as well as pathological pathways whereas the role of apoM is less explored. Hepatic apoM acts as a chaperone to transport S1P through the circulation and kidney derived apoM seems to play a role in S1P recovery to prevent urinal loss...
July 27, 2017: International Journal of Molecular Sciences
Makoto Kurano, Yutaka Yatomi
Sphingosine 1-phosphate (S1P) is a potent lipid mediator that works on five kinds of S1P receptors located on the cell membrane. In the circulation, S1P is distributed to HDL, followed by albumin. Since S1P and HDL share several bioactivities, S1P is believed to be responsible for the pleiotropic effects of HDL. Plasma S1P levels are reportedly lower in subjects with coronary artery disease, suggesting that S1P might be deeply involved in the pathogenesis of atherosclerosis. In basic experiments, however, S1P appears to possess both pro-atherosclerotic and anti-atherosclerotic properties; for example, S1P possesses anti-apoptosis, anti-inflammation, and vaso-relaxation properties and maintains the barrier function of endothelial cells, while S1P also promotes the egress and activation of lymphocytes and exhibits pro-thrombotic properties...
July 20, 2017: Journal of Atherosclerosis and Thrombosis
Wenhan Du, Ting Shen, Hui Li, Yinyin Liu, Lagu He, Li Tan, Min Hu, Yaping Ren
BACKGROUND: Sequence variation in gene promoters is often associated with disease risk. In this study, we tested the hypothesis that common promoter variation in the APOM gene is associated with systemic lupus erythematosus (SLE) risk and SLE-related clinical phenotypes in a Chinese cohort. Meanwhile, we investigated the expression of apolipoprotein M (APOM) in the serum of patients with systemic lupus erythematosus (SLE) and its relationship with disease activity. METHODS: We used a case-control design and genotyped 52 SLE patients and 52 healthy controls for 19 APOM promoter single nucleotide polymorphism (SNP) (rs113947529, rs1143030, rs114826514, rs116715239, rs12525463, rs1266078, rs2273612, rs28432254, rs34490746, rs4947251, rs55880811, rs707921, rs74890500, rs75629491, rs76611345, rs76794541, rs805264, rs805297, rs9267528)...
May 5, 2017: Lipids in Health and Disease
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