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Chem Phys Lipids. 2017 Oct;207(Pt B):246-252. doi: 10.1016/j.chemphyslip.2017.05.002. Epub 2017 May 18.

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

Author information

1
Minerva Foundation Institute for Medical Research, Helsinki, Finland.
2
Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany.
3
Minerva Foundation Institute for Medical Research, Helsinki, Finland; Systems Immunity University Research Institute and Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
4
Minerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Anatomy, Faculty of Medicine, University of Helsinki, Finland.
5
Minerva Foundation Institute for Medical Research, Helsinki, Finland. Electronic address: nidhina.haridas@helsinki.fi.

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.

KEYWORDS:

Angptl8; Ether phospholipids; Lipid storage; Lipidome; Lipolysis; Plasmalogen; Triglyceride

[Indexed for MEDLINE]

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