Long-chain fatty acids induce lipid droplet formation in a cultured human hepatocyte in a manner dependent of Acyl-CoA synthetase.

Abstract:

:Lipid droplets (LDs) are intracellular storage sites of neutral lipids, which accumulate in fatty liver disease. Here, we investigated the effects of fatty acids and glucose on LD formation in a cultured human hepatocyte, HuH7, by adding them to culture media. Fatty acids with carbohydrate chains C12-C18 efficiently induced LDs, but those of C8 and C10 were ineffective. Glucose did not induce LD formation even in the presence of insulin. Oleic acid induced significant increases in cellular neutral lipids, and cell fractionation revealed that most of the newly synthesized neutral lipids were concentrated in LDs together with LD proteins. The LD formation was not abrogated by removal of medium glucose but was significantly inhibited by an ACSL inhibitor, triacsin C. These results demonstrate that long-chain fatty acids contribute to LD formation to a greater extent than glucose, possibly by being taken up into the cells, activated by ACSL, reconstituted into neutral lipids and then stored in LDs. Pregnenolone and lithium did not suppress oleic acid-dependent LD formation, despite previous reports of their ability to inhibit LD formation in macrophages and adipocytes suggesting differences among LD formations in these cells.

journal_name

Biol Pharm Bull

authors

Fujimoto Y,Onoduka J,Homma KJ,Yamaguchi S,Mori M,Higashi Y,Makita M,Kinoshita T,Noda J,Itabe H,Takanoa T

doi

10.1248/bpb.29.2174

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

2174-80

issue

11

eissn

0918-6158

issn

1347-5215

pii

JST.JSTAGE/bpb/29.2174

journal_volume

29

pub_type

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