The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis. / Ranea-Robles, Pablo; Chen, Hongjie; Stauffer, Brandon; Yu, Chunli; Bhattacharya, Dipankar; Friedman, Scott L; Puchowicz, Michelle; Houten, Sander M.

In: Journal of Inherited Metabolic Disease, Vol. 44, No. 6, 2021, p. 1419-1433.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ranea-Robles, P, Chen, H, Stauffer, B, Yu, C, Bhattacharya, D, Friedman, SL, Puchowicz, M & Houten, SM 2021, 'The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis', Journal of Inherited Metabolic Disease, vol. 44, no. 6, pp. 1419-1433. https://doi.org/10.1002/jimd.12440

APA

Ranea-Robles, P., Chen, H., Stauffer, B., Yu, C., Bhattacharya, D., Friedman, S. L., Puchowicz, M., & Houten, S. M. (2021). The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis. Journal of Inherited Metabolic Disease, 44(6), 1419-1433. https://doi.org/10.1002/jimd.12440

Vancouver

Ranea-Robles P, Chen H, Stauffer B, Yu C, Bhattacharya D, Friedman SL et al. The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis. Journal of Inherited Metabolic Disease. 2021;44(6):1419-1433. https://doi.org/10.1002/jimd.12440

Author

Ranea-Robles, Pablo ; Chen, Hongjie ; Stauffer, Brandon ; Yu, Chunli ; Bhattacharya, Dipankar ; Friedman, Scott L ; Puchowicz, Michelle ; Houten, Sander M. / The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis. In: Journal of Inherited Metabolic Disease. 2021 ; Vol. 44, No. 6. pp. 1419-1433.

Bibtex

@article{d8876154857247e69f1ca5767d4c96ef,
title = "The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis",
abstract = "Peroxisomes metabolize a specific subset of fatty acids, which include dicarboxylic fatty acids (DCAs) generated by ω-oxidation. Data obtained in vitro suggest that the peroxisomal transporter ABCD3 (also known as PMP70) mediates the transport of DCAs into the peroxisome, but in vivo evidence to support this role is lacking. In this work, we studied an Abcd3 KO mouse model generated by CRISPR-Cas9 technology using targeted and untargeted metabolomics, histology, immunoblotting, and stable isotope tracing technology. We show that ABCD3 functions in hepatic DCA metabolism and uncover a novel role for this peroxisomal transporter in lipid homeostasis. The Abcd3 KO mouse presents with increased hepatic long-chain DCAs, increased urine medium-chain DCAs, lipodystrophy, enhanced hepatic cholesterol synthesis and decreased hepatic de novo lipogenesis. Moreover, our study suggests that DCAs are metabolized by mitochondrial fatty acid β-oxidation when ABCD3 is not functional, reflecting the importance of the metabolic compartmentalization and communication between peroxisomes and mitochondria. In summary, this study provides data on the role of the peroxisomal transporter ABCD3 in hepatic lipid homeostasis and DCA metabolism, and the consequences of peroxisomal dysfunction for the liver.",
keywords = "ATP-Binding Cassette Transporters/genetics, Animals, Dicarboxylic Acids/metabolism, Fatty Acids/metabolism, Female, Homeostasis, Lipid Metabolism, Liver/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria/metabolism, Oxidation-Reduction, Peroxisomes/metabolism",
author = "Pablo Ranea-Robles and Hongjie Chen and Brandon Stauffer and Chunli Yu and Dipankar Bhattacharya and Friedman, {Scott L} and Michelle Puchowicz and Houten, {Sander M}",
note = "{\textcopyright} 2021 SSIEM.",
year = "2021",
doi = "10.1002/jimd.12440",
language = "English",
volume = "44",
pages = "1419--1433",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer",
number = "6",

}

RIS

TY - JOUR

T1 - The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis

AU - Ranea-Robles, Pablo

AU - Chen, Hongjie

AU - Stauffer, Brandon

AU - Yu, Chunli

AU - Bhattacharya, Dipankar

AU - Friedman, Scott L

AU - Puchowicz, Michelle

AU - Houten, Sander M

N1 - © 2021 SSIEM.

PY - 2021

Y1 - 2021

N2 - Peroxisomes metabolize a specific subset of fatty acids, which include dicarboxylic fatty acids (DCAs) generated by ω-oxidation. Data obtained in vitro suggest that the peroxisomal transporter ABCD3 (also known as PMP70) mediates the transport of DCAs into the peroxisome, but in vivo evidence to support this role is lacking. In this work, we studied an Abcd3 KO mouse model generated by CRISPR-Cas9 technology using targeted and untargeted metabolomics, histology, immunoblotting, and stable isotope tracing technology. We show that ABCD3 functions in hepatic DCA metabolism and uncover a novel role for this peroxisomal transporter in lipid homeostasis. The Abcd3 KO mouse presents with increased hepatic long-chain DCAs, increased urine medium-chain DCAs, lipodystrophy, enhanced hepatic cholesterol synthesis and decreased hepatic de novo lipogenesis. Moreover, our study suggests that DCAs are metabolized by mitochondrial fatty acid β-oxidation when ABCD3 is not functional, reflecting the importance of the metabolic compartmentalization and communication between peroxisomes and mitochondria. In summary, this study provides data on the role of the peroxisomal transporter ABCD3 in hepatic lipid homeostasis and DCA metabolism, and the consequences of peroxisomal dysfunction for the liver.

AB - Peroxisomes metabolize a specific subset of fatty acids, which include dicarboxylic fatty acids (DCAs) generated by ω-oxidation. Data obtained in vitro suggest that the peroxisomal transporter ABCD3 (also known as PMP70) mediates the transport of DCAs into the peroxisome, but in vivo evidence to support this role is lacking. In this work, we studied an Abcd3 KO mouse model generated by CRISPR-Cas9 technology using targeted and untargeted metabolomics, histology, immunoblotting, and stable isotope tracing technology. We show that ABCD3 functions in hepatic DCA metabolism and uncover a novel role for this peroxisomal transporter in lipid homeostasis. The Abcd3 KO mouse presents with increased hepatic long-chain DCAs, increased urine medium-chain DCAs, lipodystrophy, enhanced hepatic cholesterol synthesis and decreased hepatic de novo lipogenesis. Moreover, our study suggests that DCAs are metabolized by mitochondrial fatty acid β-oxidation when ABCD3 is not functional, reflecting the importance of the metabolic compartmentalization and communication between peroxisomes and mitochondria. In summary, this study provides data on the role of the peroxisomal transporter ABCD3 in hepatic lipid homeostasis and DCA metabolism, and the consequences of peroxisomal dysfunction for the liver.

KW - ATP-Binding Cassette Transporters/genetics

KW - Animals

KW - Dicarboxylic Acids/metabolism

KW - Fatty Acids/metabolism

KW - Female

KW - Homeostasis

KW - Lipid Metabolism

KW - Liver/metabolism

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mitochondria/metabolism

KW - Oxidation-Reduction

KW - Peroxisomes/metabolism

U2 - 10.1002/jimd.12440

DO - 10.1002/jimd.12440

M3 - Journal article

C2 - 34564857

VL - 44

SP - 1419

EP - 1433

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

SN - 0141-8955

IS - 6

ER -

ID: 340125409