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https://www.readbyqxmd.com/read/29752428/angiopoietin-like-protein-3-angptl3-deficiency-and-familial-combined-hypolipidemia
#1
Tarugi Patrizia, Bertolini Stefano, Calandra Sebastiano
Three members of the angiopoietin-like (ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8- are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase...
April 12, 2018: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29739862/novel-gpihbp1-independent-pathway-for-clearance-of-plasma-tgs-in-angptl4-gpihbp1-mice
#2
Emily M Cushing, Kelli L Sylvers, Xun Chi, Shwetha K Shetty, Brandon Sj Davies
Mice lacking glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) are unable to traffic LPL to the vascular lumen. Thus, TG clearance is severely blunted, and mice are extremely hypertriglyceridemic. Paradoxically, mice lacking both GPIHBP1 and the LPL regulator angiopoietin-like 4 (ANGPTL4) are far less hypertriglyceridemic. We sought to determine the mechanism by which Angptl4 -/- Gpihbp1 -/- double knockout mice clear plasma triglycerides. We confirmed that, on a normal chow diet, plasma TG levels were lower in Angptl4 -/- Gpihbp1 -/- mice than in Gpihbp1 -/- mice; however, the difference disappeared with administration of a high-fat diet...
May 8, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29739381/angiopoietin-like-4-promotes-osteosarcoma-cell-proliferation-and-migration-and-stimulates-osteoclastogenesis
#3
T Zhang, A Kastrenopoulou, Q Larrouture, N A Athanasou, H J Knowles
BACKGROUND: Osteosarcoma is the most common primary bone cancer in children and young adults. It is highly aggressive and patients that present with metastasis have a poor prognosis. Angiopoietin-like 4 (ANGPTL4) drives the progression and metastasis of many solid tumours, but has not been described in osteosarcoma tissue. ANGPTL4 also enhances osteoclast activity, which is required for osteosarcoma growth in bone. We therefore investigated the expression and function of ANGPTL4 in human osteosarcoma tissue and cell lines...
May 8, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29727591/alpha-linolenic-acid-and-linoleic-acid-differentially-regulate-the-skeletal-muscle-secretome-of-obese-zucker-rats
#4
Alex Rajna, Heather Gibling, Ousseynou Sarr, Sarthak Matravadia, Graham P Holloway, David M Mutch
Evidence shows that proteins secreted from skeletal muscle influence a broad range of metabolic signaling pathways. We previously reported that essential polyunsaturated fatty acids (PUFA) improved whole-body glucose homeostasis in obese Zucker rats; however, the mechanisms underlying these benefits remain enigmatic. While PUFA and obesity influence skeletal muscle function, their effects on the secretome are unknown. The aim of this work was to determine if improvements in whole-body glucose homeostasis in obese Zucker rats fed diets supplemented with either linoleic acid (LA) or alpha-linolenic acid (ALA) for 12-wks are related to changes in the skeletal muscle secretome...
May 4, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29713054/structures-of-angptl3-and-angptl4-modulators-of-triglyceride-levels-and-coronary-artery-disease
#5
Ekaterina Biterova, Mariam Esmaeeli, Heli I Alanen, Mirva Saaranen, Lloyd W Ruddock
Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels...
April 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29695708/angiopoietin-like-protein-3-and-4-in-obesity-type-2-diabetes-mellitus-and-malnutrition-the-effect-of-weight-reduction-and-realimentation
#6
Anna Cinkajzlová, Miloš Mráz, Zdeňka Lacinová, Jana Kloučková, Petra Kaválková, Helena Kratochvílová, Pavel Trachta, Jarmila Křížová, Denisa Haluzíková, Jan Škrha, Hana Papežová, Martin Haluzík
BACKGROUND: Angiopoietin-like proteins (ANGPTLs) 3 and 4 are circulating factors that participate in the regulation of lipid and glucose metabolism. SUBJECTS AND METHODS: We measured serum ANGPTL3 and 4 levels in 23 patients with obesity, 40 patients with obesity and type 2 diabetes mellitus (T2DM), 22 patients with anorexia nervosa (AN), 15 subjects undergoing 72-h fasting, and 12 patients with short bowel syndrome (SBS), and their changes after very-low-calorie diet (VLCD), bariatric surgery, partial realimentation, acute fasting, and parenteral nutrition in order to assess their possible role in metabolic regulations...
April 25, 2018: Nutrition & Diabetes
https://www.readbyqxmd.com/read/29674661/donor-dependent-variation-of-human-umbilical-cord-blood-mesenchymal-stem-cells-in-response-to-hypoxic-preconditioning-and-amelioration-of-limb-ischemia
#7
Insung Kang, Byung-Chul Lee, Soon Won Choi, Jin Young Lee, Jae-Jun Kim, Bo-Eun Kim, Da-Hyun Kim, Seung Eun Lee, Nari Shin, Yoojin Seo, Hyung-Sik Kim, Dong-Ik Kim, Kyung-Sun Kang
With the rapidly growing demand for mesenchymal stem cell (MSC) therapy, numerous strategies using MSCs for different diseases have been studied and reported. Because of their immunosuppressive properties, MSCs are commonly used as an allogeneic treatment. However, for the many donors who could potentially be used, it is important to understand the capacity for therapeutic usage with donor-to-donor heterogeneity. In this study, we aimed to investigate MSCs as a promising therapeutic strategy for critical limb ischemia...
April 20, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29627983/fish-oil-supplementation-alleviates-the-altered-lipid-homeostasis-in-blood-liver-and-adipose-tissues-in-high-fat-diet-fed-rats
#8
Chen-Yuan Chiu, Lou-Pin Wang, Shing-Hwa Liu, Meng Tsan Chiang
This study investigated the effects of dietary supplementation of fish oil on the signals of lipid metabolism involved in hepatic cholesterol and triglyceride influx and excretion in high-fat diet (HFD)-fed rats. Fish oil (FO) repressed body (HFD: 533±18.2 g, HFD+FO: 488±28.0 g, p<0.05) and liver weights (HFD: 5.7±0.6 g/100 g body weight, HFD+FO: 4.8±0.4 g/100 g body weight, p<0.05) in HFD-fed rats. Fish oil could also improve HFD-induced imbalance of lipid metabolism in blood, liver, and adipose tissues including the significant decreases in plasma and liver total cholesterol (TC) (plasma-HFD: 113±33...
April 7, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29627378/brown-adipose-tissue-derived-angptl4-controls-glucose-and-lipid-metabolism-and-regulates-thermogenesis
#9
Abhishek K Singh, Binod Aryal, Balkrishna Chaube, Noemi Rotllan, Luis Varela, Tamas L Horvath, Yajaira Suárez, Carlos Fernández-Hernando
OBJECTIVES: Brown adipose tissue (BAT) controls triglyceride-rich lipoprotein (TRL) catabolism. This process is mediated by the lipoprotein lipase (LPL), an enzyme that catalyzed the hydrolysis of triglyceride (TAG) in glycerol and fatty acids (FA), which are burned to generate heat. LPL activity is regulated by angiopoietin-like 4 (ANGPTL4), a secretory protein produced in adipose tissues (AT), liver, kidney, and muscle. While the role of ANGPTL4 in regulating lipoprotein metabolism is well established, the specific contribution of BAT derived ANGPTL4 in controlling lipid and glucose homeostasis is not well understood...
March 29, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29621508/angiopoietin-like-3-is-a-potential-biomarker-for-retinopathy-in-type-2-diabetic-patients
#10
Cai-Guo Yu, Sha-Sha Yuan, Long-Yan Yang, Jing Ke, Li-Jie Zhang, Jia-Nan Lang, Da-Wei Zhang, Shao-Zhen Zhao, Dong Zhao, Ying-Mei Feng
PURPOSE: To investigate whether angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4) are differentially associated with the severity of retinopathy in patients with type 2 diabetes mellitus (T2DM). DESIGN: Cross-sectional study. METHODS: Serum levels of ANGPTL3, ANGPTL4, high-sensitivity C-reactive protein (CRP), vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) were quantified by ELISA...
April 2, 2018: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/29619530/can-targeting-angptl-proteins-improve-glucose-tolerance
#11
Brandon S J Davies
Three members of the angiopoietin-like (ANGPTL) family of proteins, ANGPTL3, ANGPTL4 and ANGPTL8, are known regulators of plasma triacylglycerol levels. Recently, these three proteins have garnered considerable interest as potential targets for therapeutically reducing plasma triacylglycerol levels and improving cardiovascular outcomes. In this issue of Diabetologia, Janssen et al ( https://doi.org/10.1007/s00125-018-4583-5 ) and Vatner et al ( https://doi.org/10.1007/s00125-018-4579-1 ) show that reducing levels of ANGPTL4 and ANGPTL8, respectively, could have the added benefit of improving glucose tolerance...
April 4, 2018: Diabetologia
https://www.readbyqxmd.com/read/29611540/obesity-angptl4-the-link-binding-obesity-and-glucose-intolerance
#12
Alan Morris
No abstract text is available yet for this article.
April 3, 2018: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29587751/plasma-angiopoietin-like-4-is-related-to-phospholipid-transfer-protein-activity-in-diabetic-and-non-diabetic-subjects-role-of-enhanced-low-grade-inflammation
#13
Eke G Gruppen, Sander Kersten, Robin P F Dullaart
BACKGROUND: Angiopoietin-like 4 (ANGPTL4) inhibits lipoprotein lipase, whereas phospholipid transfer protein (PLTP) enhances hepatic triglyceride secretion. Both factors may be upregulated by inflammatory pathways. Since the extent to which these circulating factors are interrelated is unknown, we determined the relationship between plasma ANGPTL4 and PLTP activity, and assessed whether such a relationship could be explained by high sensitivity C-reactive protein (hsCRP) levels as a marker of low-grade chronic inflammation...
March 27, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29563332/absence-of-angptl4-in-adipose-tissue-improves-glucose-tolerance-and-attenuates-atherogenesis
#14
Binod Aryal, Abhishek K Singh, Xinbo Zhang, Luis Varela, Noemi Rotllan, Leigh Goedeke, Balkrishna Chaube, Joao-Paulo Camporez, Daniel F Vatner, Tamas L Horvath, Gerald I Shulman, Yajaira Suárez, Carlos Fernández-Hernando
Alterations in ectopic lipid deposition and circulating lipids are major risk factors for developing cardiometabolic diseases. Angiopoietin-like protein 4 (ANGPTL4), a protein that inhibits lipoprotein lipase (LPL), controls fatty acid (FA) uptake in adipose and oxidative tissues and regulates circulating triacylglycerol-rich (TAG-rich) lipoproteins. Unfortunately, global depletion of ANGPTL4 results in severe metabolic abnormalities, inflammation, and fibrosis when mice are fed a high-fat diet (HFD), limiting our understanding of the contribution of ANGPTL4 in metabolic disorders...
March 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29555209/regulation-of-angiopoietin-like-4-and-lipoprotein-lipase-in-human-adipose-tissue
#15
Wieneke Dijk, Sophie Schutte, Edo O Aarts, Ignace M C Janssen, Lydia Afman, Sander Kersten
BACKGROUND: Elevated plasma triglycerides are increasingly viewed as a causal risk factor for coronary artery disease. One protein that raises plasma triglyceride levels and that has emerged as a modulator of coronary artery disease risk is angiopoietin-like 4 (ANGPTL4). ANGPTL4 raises plasma triglyceride levels by inhibiting lipoprotein lipase (LPL), the enzyme that catalyzes the hydrolysis of circulating triglycerides on the capillary endothelium. OBJECTIVE: The objective of the present study was to assess the association between ANGPTL4 and LPL in human adipose tissue, and to examine the influence of nutritional status on ANGPTL4 expression...
February 17, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29548670/angiopoietin-like-protein-4-a-therapeutic-target-for-triglycerides-and-coronary-disease
#16
REVIEW
David S Olshan, Daniel J Rader
The angiopoietin-like proteins are a family of proteins that share structural similarities to the angiopoietins. These proteins have been described to play a key role in the regulation of a myriad of physiologic processes, including serving as essential modulators of lipid and glucose metabolism. Angiopoietin-like protein 4 (ANGPTL4) is a key regulator of lipoprotein lipase, and its modulation has been shown to significantly impact the body's processing and distribution of triglycerides and cholesterol. Although more research remains to elucidate the full range of mechanisms through which ANGPTL4 affects triglyceride and cholesterol homeostasis, current research has associated decreased ANGPTL4 function with a beneficial effect on lipid parameters and overall cardiovascular disease risk, opening the possibility of ANGPTL4 as a new therapeutic target for the treatment of cardiovascular disease...
February 2, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29538435/association-of-circulating-angptl-3-4-and-8-levels-with-medical-status-in-a-population-undergoing-routine-medical-checkups-a-cross-sectional-study
#17
Jun Morinaga, Jiabin Zhao, Motoyoshi Endo, Tsuyoshi Kadomatsu, Keishi Miyata, Taichi Sugizaki, Yusuke Okadome, Zhe Tian, Haruki Horiguchi, Kazuya Miyashita, Nobuhiro Maruyama, Masashi Mukoyama, Yuichi Oike
PURPOSE: Angiopoietin-like proteins (ANGPTLs) 3, 4, and 8 reportedly contribute to progression of metabolic disease, a risk factor for cardiovascular disease (CVD). The purpose of this study was to investigate whether circulating ANGPTL levels are associated with CVD risk after adjustment for potential confounding factors. METHODS: We conducted a single center, cross-sectional study of 988 Japanese subjects undergoing routine health checks. Serum ANGPTL3, 4, and 8 levels were measured using an enzyme-linked immunosorbent assay...
2018: PloS One
https://www.readbyqxmd.com/read/29502266/loss-of-angiopoietin-like-4-angptl4-in-mice-with-diet-induced-obesity-uncouples-visceral-obesity-from-glucose-intolerance-partly-via-the-gut-microbiota
#18
Aafke W F Janssen, Saeed Katiraei, Barbara Bartosinska, Daniel Eberhard, Ko Willems van Dijk, Sander Kersten
AIMS/HYPOTHESIS: Angiopoietin-like 4 (ANGPTL4) is an important regulator of triacylglycerol metabolism, carrying out this role by inhibiting the enzymes lipoprotein lipase and pancreatic lipase. ANGPTL4 is a potential target for ameliorating cardiometabolic diseases. Although ANGPTL4 has been implicated in obesity, the study of the direct role of ANGPTL4 in diet-induced obesity and related metabolic dysfunction is hampered by the massive acute-phase response and development of lethal chylous ascites and peritonitis in Angptl4-/- mice fed a standard high-fat diet...
June 2018: Diabetologia
https://www.readbyqxmd.com/read/29490644/increased-plasma-and-adipose-tissue-levels-of-angptl8-betatrophin-and-angptl4-in-people-with-hypertension
#19
Mohamed Abu-Farha, Preethi Cherian, Mohamed G Qaddoumi, Irina AlKhairi, Devarajan Sriraman, Muath Alanbaei, Jehad Abubaker
BACKGROUND: Hypertension is a risk factor for both cardiovascular diseases (CVDs) and type 2 diabetes (T2D). Angiopoietin-like proteins (ANGPTLs), mainly ANGPTL3, ANGPTL4 and ANGPTL8, are associated with increased plasma lipid content due to their role in regulating the activity of lipoprotein lipase, a key enzyme in metabolism of the lipoprotein in circulation. Dyslipidaemia is a risk factor for hypertension development; however, the roles of ANGPTL3, ANGPTL4 and ANGPTL8 in subjects with hypertension have not yet been established...
March 1, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29449313/impaired-thermogenesis-and-sharp-increases-in-plasma-triglyceride-levels-in-gpihbp1-deficient-mice-during-cold-exposure
#20
Mikael Larsson, Christopher M Allan, Patrick J Heizer, Yiping Tu, Norma P Sandoval, Rachel S Jung, Rosemary L Walzem, Anne P Beigneux, Stephen G Young, Loren G Fong
Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1), an endothelial cell protein, binds LPL in the subendothelial spaces and transports it to the capillary lumen. In Gpihbp1 -/- mice, LPL remains stranded in the subendothelial spaces, causing hypertriglyceridemia, but how Gpihbp1 -/- mice respond to metabolic stress (e.g., cold exposure) has never been studied. In wild-type mice, cold exposure increases LPL-mediated processing of triglyceride-rich lipoproteins (TRLs) in brown adipose tissue (BAT), providing fuel for thermogenesis and leading to lower plasma triglyceride levels...
April 2018: Journal of Lipid Research
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