Profiling and Imaging of Phospholipids in Brains of Abcd1-Deficient Mice.

Abstract

ABCD1 is a gene responsible for X-linked adrenoleukodystrophy (X-ALD), and is critical for the transport of very long-chain fatty acids (VLCFA) into peroxisomes and subsequent β-oxidation. VLCFA-containing lipids accumulate in X-ALD patients, although the effect of ABCD1-deficiency on each lipid species in the central nervous system has not been fully characterized. In this study, each phospholipid and lysophospholipid species in Abcd1-deficient mice brains were profiled by liquid chromatography-mass spectrometry. Among the phospholipid and lysophospholipid species that are significantly more enriched in Abcd1-deficient mice brains, VLCFA were present in 75, 15, 5, 4, and 1 species of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, lysophosphatidylcholine, and lysophosphatidylethanolamine, respectively. Most VLCFA were incorporated at the sn-1 position of phosphatidylcholine and phosphatidylethanolamine. Among the phospholipid species that are significantly less enriched in Abcd1-deficient mice brains, odd-numbered saturated or mono-unsaturated fatty acyl moieties are contained in all phosphatidylcholine species. In addition, a number of phosphatidylglycerol, phosphatidylinositol, and phosphatidylserine species contained highly unsaturated fatty acyl moieties. Intriguingly, 44:1 phosphatidylcholine with VLCFA was mainly distributed in the gray matter, such as the cortex, but not in the white matter in the cerebrum and cerebellum. These results show that ABCD1-deficiency causes metabolic alternation of long-chain fatty acids and VLCFA. Moreover, our results imply a molecular mechanism for the incorporation of saturated or monounsaturated VLCFA into the sn-1 position of phospholipids, and also indicate that the distribution of phospholipids with VLCFA may correlate with the development of X-ALD.

• Authors: Kotaro Hama, Yuko Fujiwara, Masashi Morita, Fumiyoshi Yamazaki, Yuko Nakashima, Shiro Takei, Shigeo Takashima, Mitsutoshi Setou, Nobuyuki Shimozawa, Tsuneo Imanaka, Kazuaki Yokoyama
• Journal: Lipids (Lipids) Vol. 53 Issue 1 Pg. 85-102 (01 2018) ISSN: 1558-9307 [Electronic] United States
• PMID: 29469952 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Lipids published by AOCS.

Chemical References

• ATP Binding Cassette Transporter, Subfamily D, Member 1
• Abcd1 protein, mouse
• Fatty Acids
• Phosphatidylcholines
• Phospholipids

Topics

• ATP Binding Cassette Transporter, Subfamily D, Member 1 (genetics)
• Adrenoleukodystrophy (genetics, metabolism, pathology)
• Animals
• Brain (metabolism)
• Disease Models, Animal
• Fatty Acids (biosynthesis, genetics)
• Fibroblasts (metabolism)
• Humans
• Lipid Peroxidation
• Mice
• Oxidation-Reduction
• Peroxisomes (genetics, metabolism)
• Phosphatidylcholines (metabolism)
• Phospholipids (biosynthesis, metabolism)