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

Mysore, Raghavendra, Liebisch, Gerhard, Zhou, You ORCID: https://orcid.org/0000-0002-1743-1291, Olkkonen, Vesa M. and Nidhina Haridas, P.A. 2017. Angiopoietin-like 8 (Angptl8) controls adipocyte lipolysis and phospholipid composition. Chemistry and Physics of Lipids 207 (B) , pp. 246-252. 10.1016/j.chemphyslip.2017.05.002

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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 (NEFAs). Consistently, mRNAs encoding Angptl4 and Leptin, which facilitate lipolysis, as well as Cpt1a, Cpt1b, and Pgc-1α involved in FA oxidation, were elevated. The Angptl8 mRNA itself was suppressed by pharmacologic treatments inducing lipolysis: stimulation with the β-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. Abbreviation Angptl8, angiopoietin-like 8; FA, fatty acid; LD, lipid droplet; LPL, lipoprotein lipase; NEFA, non-esterified FA; PC, phosphatidylcholine; PE, phosphatidylethanolamine; qPCR, quantitative reverse transcriptase PCR; shRNA, short hairpin RNA; TG, triglyceride; WAT, white adipose tissue

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Angptl8; Lipidome; Lipid storage; Lipolysis; Plasmalogen; Triglyceride; Ether phospholipids
Publisher:	Elsevier
ISSN:	0009-3084
Date of First Compliant Deposit:	21 June 2017
Date of Acceptance:	15 May 2017
Last Modified:	10 Nov 2023 15:36
URI:	https://orca.cardiff.ac.uk/id/eprint/101632

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