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Exp Cell Res. 2017 Sep 15;358(2):397-410. doi: 10.1016/j.yexcr.2017.07.015. Epub 2017 Jul 14.

Role of hepatic Annexin A6 in fatty acid-induced lipid droplet formation.

Author information

1
Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
2
Departament de Biomedicina, Unitat de Biologia Cel·lular, Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, Spain.
3
Discipline of Physiology, School of Medical Science & Bosch Institute; Sydney Medical School; Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia.
4
Urology Research Laboratory, Department Clinical Research, University of Bern, 3010 Bern, Switzerland.
5
Department of Internal Medicine I, Regensburg University Hospital, 93042 Regensburg, Germany.
6
Departament de Biomedicina, Unitat de Biologia Cel·lular, Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, Spain. Electronic address: carles.rentero@ub.edu.
7
Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia. Electronic address: thomas.grewal@sydney.edu.au.

Abstract

Annexin A6 (AnxA6) has been implicated in the regulation of endo-/exocytic pathways, cholesterol transport, and the formation of multifactorial signaling complexes in many different cell types. More recently, AnxA6 has also been linked to triglyceride storage in adipocytes. Here we investigated the potential role of AnxA6 in fatty acid (FA) - induced lipid droplet (LD) formation in hepatocytes. AnxA6 was associated with LD from rat liver and HuH7 hepatocytes. In oleic acid (OA) -loaded HuH7 cells, substantial amounts of AnxA6 bound to LD in a Ca2+-independent manner. Remarkably, stable or transient AnxA6 overexpression in HuH7 cells led to elevated LD numbers/size and neutral lipid staining under control conditions as well as after OA loading compared to controls. In contrast, overexpression of AnxA1, AnxA2 and AnxA8 did not impact on OA-induced lipid accumulation. On the other hand, incubation of AnxA6-depleted HuH7 cells or primary hepatocytes from AnxA6 KO-mice with OA led to reduced FA accumulation and LD numbers. Furthermore, morphological analysis of liver sections from A6-KO mice revealed significantly lower LD numbers compared to wildtype animals. Interestingly, pharmacological inhibition of cytoplasmic phospholipase A2α (cPLA2α)-dependent LD formation was ineffective in AnxA6-depleted HuH7 cells. We conclude that cPLA2α-dependent pathways contribute to the novel regulatory role of hepatic AnxA6 in LD formation.

KEYWORDS:

Annexin A6; Cytoplasmic phospholipase A2; Fatty acid; Hepatocytes; Lipid droplets

PMID:
28712927
DOI:
10.1016/j.yexcr.2017.07.015
[Indexed for MEDLINE]

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