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Lipid Analysis Reveals Quiescent and Regenerating Liver-Specific Populations of Lipid Droplets

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Lipids

Abstract

The mammalian liver, a key organ in lipid homeostasis, can accumulate increased amounts of lipids in certain physiological conditions including liver regeneration. Lipid droplets (LD), the lipid storage organelles in the cytoplasm, are composed of a core of neutral lipids (mainly triacylglycerols and cholesteryl esters) surrounded by a monolayer of phospholipids and cholesterol with associated proteins. It is recognized that LD lipid composition is cell- and environment-specific and enables LD to carry out specific functions, but few descriptive studies aiming to interpret such differences have been published. We characterized eight density fractions of LD isolated from quiescent (control) and regenerating liver after partial hepatectomy, and grouped populations according to their lipid composition. LD from quiescent liver resembled the cholesteryl ester storage LD found in steroidogenic tissues, whereas in the regenerating tissue they were similar to adipocyte LD. Specifically, there were large, light LD with increased triacylglycerol content, the hallmark of liver regeneration. The apparent volume of the dense LD was, however, lower than in the quiescent density-matched populations, concomitant with increased phosphatidylcholine and phosphatidylethanolamine and decreased neutral lipid content. Analysis of the lipid profile of LD populations from quiescent and regenerating tissue leads us to define four physiological LD phenotypes for rat liver.

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Abbreviations

C:

Unesterified free cholesterol

CE:

Cholesterol ester(s)

LD:

Lipid droplet(s)

PtdCho:

Phosphatidylcholine

PtdEtn:

Phosphatidylethanolamine

PH:

Partial hepatectomy

PtdIns:

Phosphatidylinositol

PL:

Phospholipid(s)

PNSN:

Postnuclear supernatant

PtdSer:

Phosphatidylserine

CerPCho:

Sphingomyelin

TAG:

Triacylglycerol

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Acknowledgments

Research was supported by grants from the Spanish National Ministry for Education and Science (SAF2007/60211) and the Basque Government (Saiotek program and IT-325-07). I.G-A. was recipient of a research training fellowship from the Basque Government.

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Correspondence to Olatz Fresnedo.

Electronic Supplementary Material

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Supplementary Fig. 1. Identification of isolated lipid droplet populations in quiescent and regenerating rat liver.

a. Postnuclear supernatant (PNSN) from quiescent and regenerating rat liver (0.32 g) was fractionated on a sucrose gradient as described in Material and Methods (depicted in Fig. 2 of the manuscript). Eight fractions, harvested from the top of the gradient, and microsomes as a negative control were probed with antibodies against the lipid droplet marker adipophilin (ADRP), the Golgi marker GM-130, and the endoplasmic reticulum marker calregulin. It was confirmed that fractions 1–8 were adipophilin(+) lipid droplets, without visible contamination. (TIFF 811 kb)

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García-Arcos, I., González-Kother, P., Aspichueta, P. et al. Lipid Analysis Reveals Quiescent and Regenerating Liver-Specific Populations of Lipid Droplets. Lipids 45, 1101–1108 (2010). https://doi.org/10.1007/s11745-010-3492-2

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