Angiopoietin-like 8 (Angptl8) controls adipocyte lipolysis and phospholipid composition

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http://hdl.handle.net/10138/298088

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Mysore , R , Liebisch , G , Zhou , Y , Olkkonen , V M & Haridas , P A N 2017 , ' Angiopoietin-like 8 (Angptl8) controls adipocyte lipolysis and phospholipid composition ' , Chemistry and Physics of Lipids , vol. 207 , pp. 246-252 . https://doi.org/10.1016/j.chemphyslip.2017.05.002

Title: Angiopoietin-like 8 (Angptl8) controls adipocyte lipolysis and phospholipid composition
Author: Mysore, Raghavendra; Liebisch, Gerhard; Zhou, You; Olkkonen, Vesa M.; Haridas, P. A. Nidhina
Contributor: University of Helsinki, Medicum
Date: 2017-10
Language: eng
Number of pages: 7
Belongs to series: Chemistry and Physics of Lipids
ISSN: 0009-3084
URI: http://hdl.handle.net/10138/298088
Abstract: Angiopoietin-like 8 (Angptl8) inhibits lipolysis in the circulation together with Angplt3 and controls post-prandial fat storage in white adipose tissue (WAT). It is strongly induced by insulin in vivo in WAT and in vitro in adipocytes. In this study we addressed the function of Angptl8 in adipocytes by its stable lentivirus-mediated knock-down in 3T3-L1 cells, followed by analyses of triglyceride (TG) storage, lipid droplet (LD) morphology, the cellular lipidome, lipolysis, and gene expression. Depletion of Angptl8 did not drastically affect the adipocyte differentiation of 3T3-L1 cells but resulted in a moderate (18-19%) reduction of stored TGs. The lipidome analysis revealed a reduction of alkyl-phosphatidylcholines (PCs) and phosphatidylethanolamine (PE) plasmalogens, as well as saturated PCs and PEs. Importantly, the Angptl8 depleted cells displayed enhanced lipolysis as measured by release of non-esterified fatty acids (NEFA5). Consistently, mRNAs encoding Angptl4 and Leptin, which facilitate lipolysis, as well as Cpt1a, Cpt1b, and Pgc-1 alpha involved in FA oxidation, were elevated. The Angptl8 mRNA itself was suppressed by pharmacologic treatments inducing lipolysis: stimulation with the beta-adrenergic agonist isoproterenol or with the adenylate cyclase activator forskolin. To conclude, knock-down of Angptl8 in adipocytes suggests that the protein acts to inhibit intracellular lipolysis, analogous to its activity in the circulation. Depletion of Angptl8 results in an altered cellular phospholipid composition. The findings identify Angptl8 as a central insulin-regulated controller of adipocyte lipid metabolism. (C) 2017 Elsevier B.V. All rights reserved.
Subject: Angptl8
Lipidome
Lipid storage
Lipolysis
Plasmalogen
Triglyceride
Ether phospholipids
TANDEM MASS-SPECTROMETRY
HIGH-THROUGHPUT QUANTIFICATION
INSULIN-RESISTANCE
LIPID-METABOLISM
ADIPOSE-TISSUE
PROTEIN
LEPTIN
BETATROPHIN
EXPRESSION
GLUCOSE
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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