ABCA7 Regulates Brain Fatty Acid Metabolism During LPS-Induced Acute Inflammation

Tomonori Aikawa, Yingxue Ren, Marie Louise Holm, Yan W. Asmann, Amer Alam, Michael L. Fitzgerald, Guojun Bu, Takahisa Kanekiyo

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


The ATP binding cassette subfamily A member 7 (ABCA7) gene is one of the significant susceptibility loci for Alzheimer’s disease (AD). Furthermore, ABCA7 loss of function variants resulting from premature termination codon in the gene are associated with increased risk for AD. ABCA7 belongs to the ABC transporter family, which mediates the transport of diverse metabolites across the cell membrane. ABCA7 is also involved in modulating immune responses. Because the immune system and lipid metabolism causatively engage in the pathogenesis of AD, we investigated how ABCA7 haplodeficiency modulates the metabolic profile in mouse brains during acute immune response using a metabolomics approach through LC/Q-TOF-MS. Peripheral lipopolysaccharide (LPS) stimulation substantially influenced the metabolite content in the cortex, however, the effect on metabolic profiles in Abca7 heterozygous knockout mice (Abca7±) was modest compared to that in the control wild-type mice. Weighted gene co-expression network analysis (WGCNA) of the metabolomics dataset identified two modules influenced by LPS administration and ABCA7 haplodeficiency, in which glycerophospholipid metabolism, linoleic acid metabolism, and α-linolenic acid metabolism were identified as major pathways. Consistent with these findings, we also found that LPS stimulation increased the brain levels of eicosapentaenoic acid, oleic acid, and palmitic acid in Abca7± mice, but not control mice. Together, our results indicate that ABCA7 is involved in the crosstalk between fatty acid metabolism and inflammation in the brain, and disturbances in these pathways may contribute to the risk for AD.

Original languageEnglish (US)
Article number647974
JournalFrontiers in Neuroscience
StatePublished - Apr 7 2021

Bibliographical note

Funding Information:
This work was supported by NIH grants (R21AG054890 to TK and R37AG027924, R01AG035355, RF1AG056130, and RF1AG051504 to GB) and Cure Alzheimer’s Fund (to GB and TK). This publication was also made possible by Mayo Clinic Metabolomics Resource Core through grant number U24DK100469 from the National Institute of Diabetes and Digestive and Kidney Diseases and originates from the NIH Director’s Common Fund.

Publisher Copyright:
© Copyright © 2021 Aikawa, Ren, Holm, Asmann, Alam, Fitzgerald, Bu and Kanekiyo.


  • ABCA7
  • Alzheimer’s disease
  • fatty acids
  • inflammation
  • lipopolysaccharide
  • metabolomics


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