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Both full‐length and exon 9‐deleted human cholesteryl ester transfer protein isoforms are involved in cellular lipid homeostasis
Author(s) -
Izem Lahoucine,
Morton Richard E
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1020.2
Subject(s) - cholesterylester transfer protein , lipid metabolism , gene isoform , chemistry , lipid droplet , cholesteryl ester , efflux , biochemistry , cholesterol , lipoprotein , gene
In humans, cholesteryl ester transfer protein (CETP) exists as full‐length (FL) and exon 9‐deleted (E9) isoforms. The E9 variant is retained by cells while FL CETP is largely secreted. We reported before that simultaneously inhibiting both FL and E9 CETP synthesis in SW872 human adipocytes disrupts their lipid metabolism. To further investigate the roles of these two isoforms in cellular lipid metabolism, we stably expressed each isoform in human cells that naturally have CETP and mouse cells that lack CETP. The expression of FL‐CETP in mouse 3T3‐L1 cells increased their droplet cholesteryl ester (CE) content by 2 fold and their lipid efflux capacity by more than 20%. Expressing E9 CETP increased CE and triglyceride (TG) by 17% and 30% respectively. In human SW872 cells overexpressing FL‐CETP, lipid efflux was increased 2‐fold compared to control, but they stored 50% less TG in smaller, more numerous lipid storage droplets. Overexpression of E9‐CETP reduced the amount of secreted FL‐CETP by 75% and increased their CE and TG content by 2 fold, which can be partly explained by a significant reduction in lipid efflux and a slight increase in TG synthesis. In vitro, while E9 CETP blocks completely the FL‐CETP mediated transfer of lipids between organelles, E9 CETP showed some lipid transfer activity on its own. Collectively, our data implicate both FL‐length and E9 CETP in modulating cellular lipid metabolism. NIH HL 060934