The negative effect of ANGPTL8 on HDL-mediated cholesterol efflux capacity. 2018

Mengdie Luo, and Ziyu Zhang, and Yani Peng, and Shuai Wang, and Daoquan Peng
Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, No.139, Middle Renmin Road, Changsha, 410011, Hunan, China.

It is well known that angiopoietin-like protein 8 (ANGPTL8) exerts its effects on lipid metabolism through the inhibition of lipoprotein lipase and subsequent elevation of plasma triglyceride. However, it is not clear whether ANGPTL8 could affect lipid metabolism via other pathways. The study was aimed to investigate the effects of ANGPTL8 on the function of high-density lipoprotein (HDL), which plays a protective role in atherosclerosis progression. Two hundred and ten subjects were recruited. Plasma ANGPTL8 was measured by enzyme-linked immunosorbent assays. Cholesterol efflux capacity was chosen as the biomarker of HDL function and measured via H3-cholesterol loading THP-1 cell models. ANGPTL8 exhibited no significant difference between CAD group and nonCAD group, but ANGPTL8 in DM group was significantly higher than that in the nonDM group [568.3 (406.2-836.8) vs 458.2 (356.8-755.6), P = 0.023]. Compared to controls, subjects in CAD group and DM group exhibited significantly lower cholesterol efflux capacity [CAD: 14.58 ± 2.06 vs 12.51 ± 2.83%, P < 0.0001; DM: 13.62 ± 2.57 vs 12.34 ± 3.16%, P = 0.0099]. ANGPTL8 was inversely correlated with cholesterol efflux capacity (r = - 0.188, P < 0.01). Regression analysis revealed that plasma ANGPTL8 was an independent contributor to cholesterol efflux capacity (standardized β = - 0.143, P = 0.023). ANGPTL8 presents a negative effect on HDL-mediated cholesterol efflux capacity.

UI MeSH Term Description Entries
D008076 Cholesterol, HDL Cholesterol which is contained in or bound to high-density lipoproteins (HDL), including CHOLESTEROL ESTERS and free cholesterol. High Density Lipoprotein Cholesterol,Cholesterol, HDL2,Cholesterol, HDL3,HDL Cholesterol,HDL(2) Cholesterol,HDL(3) Cholesterol,HDL2 Cholesterol,HDL3 Cholesterol,alpha-Lipoprotein Cholesterol,Cholesterol, alpha-Lipoprotein,alpha Lipoprotein Cholesterol
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D003924 Diabetes Mellitus, Type 2 A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY. Diabetes Mellitus, Adult-Onset,Diabetes Mellitus, Ketosis-Resistant,Diabetes Mellitus, Maturity-Onset,Diabetes Mellitus, Non-Insulin-Dependent,Diabetes Mellitus, Slow-Onset,Diabetes Mellitus, Stable,MODY,Maturity-Onset Diabetes Mellitus,NIDDM,Diabetes Mellitus, Non Insulin Dependent,Diabetes Mellitus, Noninsulin Dependent,Diabetes Mellitus, Noninsulin-Dependent,Diabetes Mellitus, Type II,Maturity-Onset Diabetes,Noninsulin-Dependent Diabetes Mellitus,Type 2 Diabetes,Type 2 Diabetes Mellitus,Adult-Onset Diabetes Mellitus,Diabetes Mellitus, Adult Onset,Diabetes Mellitus, Ketosis Resistant,Diabetes Mellitus, Maturity Onset,Diabetes Mellitus, Slow Onset,Diabetes, Maturity-Onset,Diabetes, Type 2,Ketosis-Resistant Diabetes Mellitus,Maturity Onset Diabetes,Maturity Onset Diabetes Mellitus,Non-Insulin-Dependent Diabetes Mellitus,Noninsulin Dependent Diabetes Mellitus,Slow-Onset Diabetes Mellitus,Stable Diabetes Mellitus
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074084 THP-1 Cells A human leukemia monocytic cell line derived from a patient with LEUKEMIA, MONOCYTIC, ACUTE. It is used as a model to study the function of MONOCYTES and MACROPHAGES, their signaling pathways, nutrient and drug transport. THP-1 Cell Line,Cell Line, THP-1,Cell Lines, THP-1,Cell, THP-1,Cells, THP-1,THP 1 Cell Line,THP 1 Cells,THP-1 Cell,THP-1 Cell Lines
D000075802 Angiopoietin-like Proteins A family of proteins that is structurally similar to ANGIOPOIETINS but do not bind angiopoietin receptors. They are characterized by an amino-terminal coiled-coil domain, a linker region, and a carboxy-terminal FIBRINOGEN-like domain with the exception of ANGPTL8, which lacks the fibrinogen-like domain. They function in a variety of developmental and physiological processes, including INFLAMMATION, lipid metabolism, hematopoietic stem cell activity, and cancer metastasis. Angiopoietin-like Protein,Angiopoietin-related Protein,Angiopoietin like Protein,Angiopoietin like Proteins,Angiopoietin related Protein
D000091306 Angiopoietin-Like Protein 8 A nutritionally-regulated factor found in the LIVER. It plays a role in lipid metabolism and VLDL secretion in the liver. It was originally called betatrophin due to its suspected role as a peptide hormone that stimulates beta cell proliferation. Betatrophin,Angiopoietin Like Protein 8

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