Knockdown of FABP5 mRNA decreases cellular cholesterol levels and results in decreased apoB100secretion and triglyceride accumulation in ARPE-19 cells

Tinghuai Wu; Jane Tian; Roy G. Cutler; Richard S. Telljohann; David A. Bernlohr; Mark P. Mattson; James T. Handa

doi:10.1038/labinvest.2009.33

Knockdown of FABP5 mRNA decreases cellular cholesterol levels and results in decreased apoB100secretion and triglyceride accumulation in ARPE-19 cells

Tinghuai Wu, Jane Tian, Roy G. Cutler, Richard S. Telljohann, David A. Bernlohr, Mark P. Mattson, James T. Handa

Metabolic and Systems Biology (BMBB)

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

To maintain normal retinal function, retinal pigment epithelial (RPE) cells engulf photoreceptor outer segments (ROS) enriched in free fatty acids (FFAs). We have previously demonstrated fatty acid-binding protein 5 (FABP5) downregulation in the RPE/choroidal complex in a mouse model of aging and early age-related macular degeneration. FABPs are involved in intracellular transport of FFAs and their targeting to specific metabolic pathways. To elucidate the role of FABP5 in lipid metabolism, the production of the FABP5 protein in a human RPE cell line was inhibited using RNA interference technology. As a result, the levels of cholesterol and cholesterol ester were decreased by about 40%, whereas FFAs and triglycerides were increased by 18 and 67% after siRNA treatment, respectively. Some species of phospholipids were decreased in siRNA-treated cells. Cellular lipid droplets were evident and apoB secretion was decreased by 76% in these cells. Additionally, we discovered that ARPE-19 cells could synthesize and secrete Apolipoprotein B100 (apoB100), which may serve as a backbone structure for the formation of lipoprotein particles in these cells. Our results indicate that FABP5 mRNA knockdown results in the accumulation of cellular triglycerides, decreased cholesterol levels, and reduced secretion of apoB100 protein and lipoprotein-like particles. These observations indicated that FABP5 plays a critical role in lipid metabolism in RPE cells, suggesting that FABP5 downregulation in the RPE/choroid complex in vivo might contribute to aging and early age-related macular degeneration.

Original language	English (US)
Pages (from-to)	906-914
Number of pages	9
Journal	Laboratory Investigation
Volume	90
Issue number	6
DOIs	https://doi.org/10.1038/labinvest.2009.33
State	Published - Jun 2010

Bibliographical note

Funding Information:
This work was supported by NEI EY 14005 (JTH), an AHAF Macular Degeneration Grant (JTH), a Research to Prevent Blindness Clinician Scientist award (JTH), an unrestricted RPB grant, the Intramural Research Program of the National Insitute on Aging, DK053189 (DAB), and gifts from Ric and Sandy Forsythe, The Kwok family the Merlau family, and Aleda Wright.

Keywords

ApoB
Cholesterol
FABP5
RPE
SiRNA
Triglycerides

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{78015290fb2048049eb94dd52b5474c3,

title = "Knockdown of FABP5 mRNA decreases cellular cholesterol levels and results in decreased apoB100secretion and triglyceride accumulation in ARPE-19 cells",

abstract = "To maintain normal retinal function, retinal pigment epithelial (RPE) cells engulf photoreceptor outer segments (ROS) enriched in free fatty acids (FFAs). We have previously demonstrated fatty acid-binding protein 5 (FABP5) downregulation in the RPE/choroidal complex in a mouse model of aging and early age-related macular degeneration. FABPs are involved in intracellular transport of FFAs and their targeting to specific metabolic pathways. To elucidate the role of FABP5 in lipid metabolism, the production of the FABP5 protein in a human RPE cell line was inhibited using RNA interference technology. As a result, the levels of cholesterol and cholesterol ester were decreased by about 40%, whereas FFAs and triglycerides were increased by 18 and 67% after siRNA treatment, respectively. Some species of phospholipids were decreased in siRNA-treated cells. Cellular lipid droplets were evident and apoB secretion was decreased by 76% in these cells. Additionally, we discovered that ARPE-19 cells could synthesize and secrete Apolipoprotein B100 (apoB100), which may serve as a backbone structure for the formation of lipoprotein particles in these cells. Our results indicate that FABP5 mRNA knockdown results in the accumulation of cellular triglycerides, decreased cholesterol levels, and reduced secretion of apoB100 protein and lipoprotein-like particles. These observations indicated that FABP5 plays a critical role in lipid metabolism in RPE cells, suggesting that FABP5 downregulation in the RPE/choroid complex in vivo might contribute to aging and early age-related macular degeneration.",

keywords = "ApoB, Cholesterol, FABP5, RPE, SiRNA, Triglycerides",

author = "Tinghuai Wu and Jane Tian and Cutler, {Roy G.} and Telljohann, {Richard S.} and Bernlohr, {David A.} and Mattson, {Mark P.} and Handa, {James T.}",

note = "Funding Information: This work was supported by NEI EY 14005 (JTH), an AHAF Macular Degeneration Grant (JTH), a Research to Prevent Blindness Clinician Scientist award (JTH), an unrestricted RPB grant, the Intramural Research Program of the National Insitute on Aging, DK053189 (DAB), and gifts from Ric and Sandy Forsythe, The Kwok family the Merlau family, and Aleda Wright.",

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AU - Tian, Jane

AU - Cutler, Roy G.

AU - Telljohann, Richard S.

AU - Bernlohr, David A.

AU - Mattson, Mark P.

AU - Handa, James T.

N1 - Funding Information: This work was supported by NEI EY 14005 (JTH), an AHAF Macular Degeneration Grant (JTH), a Research to Prevent Blindness Clinician Scientist award (JTH), an unrestricted RPB grant, the Intramural Research Program of the National Insitute on Aging, DK053189 (DAB), and gifts from Ric and Sandy Forsythe, The Kwok family the Merlau family, and Aleda Wright.

PY - 2010/6

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N2 - To maintain normal retinal function, retinal pigment epithelial (RPE) cells engulf photoreceptor outer segments (ROS) enriched in free fatty acids (FFAs). We have previously demonstrated fatty acid-binding protein 5 (FABP5) downregulation in the RPE/choroidal complex in a mouse model of aging and early age-related macular degeneration. FABPs are involved in intracellular transport of FFAs and their targeting to specific metabolic pathways. To elucidate the role of FABP5 in lipid metabolism, the production of the FABP5 protein in a human RPE cell line was inhibited using RNA interference technology. As a result, the levels of cholesterol and cholesterol ester were decreased by about 40%, whereas FFAs and triglycerides were increased by 18 and 67% after siRNA treatment, respectively. Some species of phospholipids were decreased in siRNA-treated cells. Cellular lipid droplets were evident and apoB secretion was decreased by 76% in these cells. Additionally, we discovered that ARPE-19 cells could synthesize and secrete Apolipoprotein B100 (apoB100), which may serve as a backbone structure for the formation of lipoprotein particles in these cells. Our results indicate that FABP5 mRNA knockdown results in the accumulation of cellular triglycerides, decreased cholesterol levels, and reduced secretion of apoB100 protein and lipoprotein-like particles. These observations indicated that FABP5 plays a critical role in lipid metabolism in RPE cells, suggesting that FABP5 downregulation in the RPE/choroid complex in vivo might contribute to aging and early age-related macular degeneration.

AB - To maintain normal retinal function, retinal pigment epithelial (RPE) cells engulf photoreceptor outer segments (ROS) enriched in free fatty acids (FFAs). We have previously demonstrated fatty acid-binding protein 5 (FABP5) downregulation in the RPE/choroidal complex in a mouse model of aging and early age-related macular degeneration. FABPs are involved in intracellular transport of FFAs and their targeting to specific metabolic pathways. To elucidate the role of FABP5 in lipid metabolism, the production of the FABP5 protein in a human RPE cell line was inhibited using RNA interference technology. As a result, the levels of cholesterol and cholesterol ester were decreased by about 40%, whereas FFAs and triglycerides were increased by 18 and 67% after siRNA treatment, respectively. Some species of phospholipids were decreased in siRNA-treated cells. Cellular lipid droplets were evident and apoB secretion was decreased by 76% in these cells. Additionally, we discovered that ARPE-19 cells could synthesize and secrete Apolipoprotein B100 (apoB100), which may serve as a backbone structure for the formation of lipoprotein particles in these cells. Our results indicate that FABP5 mRNA knockdown results in the accumulation of cellular triglycerides, decreased cholesterol levels, and reduced secretion of apoB100 protein and lipoprotein-like particles. These observations indicated that FABP5 plays a critical role in lipid metabolism in RPE cells, suggesting that FABP5 downregulation in the RPE/choroid complex in vivo might contribute to aging and early age-related macular degeneration.

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KW - SiRNA

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Knockdown of FABP5 mRNA decreases cellular cholesterol levels and results in decreased apoB100secretion and triglyceride accumulation in ARPE-19 cells

Abstract

Bibliographical note

Keywords

UN SDGs

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