Both full length-cholesteryl ester transfer protein and exon 9-deleted cholesteryl ester transfer protein promote triacylglycerol storage in cultured hepatocytes.
cellular lipid homeostasis
cholesteryl ester transfer protein
hepatocyte
isoforms
lipid metabolism
triacylglycerol
Journal
Lipids
ISSN: 1558-9307
Titre abrégé: Lipids
Pays: United States
ID NLM: 0060450
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
22
11
2021
received:
15
07
2021
accepted:
23
11
2021
pubmed:
7
12
2021
medline:
28
1
2022
entrez:
6
12
2021
Statut:
ppublish
Résumé
We previously reported that overexpression of full-length cholesteryl ester transfer protein (FL-CETP), but not its exon 9-deleted variant (∆E9-CETP), in an adipose cell line reduces their triacylglycerol (TAG) content. This provided mechanistic insight into several in vivo studies where FL-CETP levels are inversely correlated with adiposity. However, increased FL-CETP is also associated with elevated hepatic lipids, suggesting that the effect of CETP on cellular lipid metabolism may be tissue-specific. Here, we directly investigated the role of FL-CETP and ∆E9-CETP in hepatic lipid metabolism. FL- or ∆E9-CETP was overexpressed in HepG2-C3A by adenovirus transduction. Overexpression of either FL or ∆E9-CETP in hepatocytes increased cellular TAG mass by 25% but reduced TAG secretion. This cellular TAG was contained in larger and more numerous lipid droplets. Analysis of TAG synthetic and catabolic pathways showed that this elevated TAG content was due to increased incorporation of fatty acid into TAG (24%), and higher de novo synthesis of fatty acid (50%) and TAG from acetate (40%). siRNA knockdown of CETP had the opposite effect on TAG synthesis and lipogenesis, and decreased cellular TAG. This novel increase in cellular TAG by FL-CETP overexpression was reproduced in Caco-2 intestinal epithelial cells. We conclude that, unlike that seen in adipocyte cells, overexpression of either CETP isoform in lipoprotein-secreting cells promotes the accumulation of TAG. These data suggest that the in vivo correlation between CETP levels and hepatic steatosis can be explained, in part, by a direct effect of CETP on hepatocyte cellular metabolism.
Identifiants
pubmed: 34866179
doi: 10.1002/lipd.12330
pmc: PMC9060302
mid: NIHMS1773171
doi:
Substances chimiques
CETP protein, human
0
Cholesterol Ester Transfer Proteins
0
Cholesterol Esters
0
Triglycerides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
69-79Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL130041
Pays : United States
Informations de copyright
© 2021 AOCS.
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