TY - JOUR
T1 - Reelin deficiency leads to aberrant lipid composition in mouse brain
AU - Mizukami, Tomoharu
AU - Ikeda, Kazutaka
AU - Shimanaka, Yuta
AU - Korogi, Katsunari
AU - Zhou, Chunyu
AU - Takase, Hiroshi
AU - Tsuiji, Hitomi
AU - Kono, Nozomu
AU - Kohno, Takao
AU - Arai, Hiroyuki
AU - Arita, Makoto
AU - Hattori, Mitsuharu
N1 - Funding Information:
The authors declare no competing financial interests. This work was supported by MEXT KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas “LipoQuality” ( 16H01366 to M.H., 15H05897 and 15H05898 to M.A.), JSPS KAKENHI ( 17H03895 and 17K19500 to M.H.), and Ono Medical Research Foundation (to M.H.).
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/10/20
Y1 - 2018/10/20
N2 - Reelin is a secreted protein essential for the development and function of the mammalian brain. The receptors for Reelin, apolipoprotein E receptor 2 and very low-density lipoprotein receptor, belong to the low-density lipoprotein receptor family, but it is not known whether Reelin is involved in the brain lipid metabolism. In the present study, we performed lipidomic analysis of the cerebral cortex of wild-type and Reelin-deficient (reeler) mice, and found that reeler mice exhibited several compositional changes in phospholipids. First, the ratio of phospholipids containing one saturated fatty acid (FA) and one docosahexaenoic acid (DHA) or arachidonic acid (ARA) decreased. Secondly, the ratio of phospholipids containing one monounsaturated FA (MUFA) and one DHA or ARA increased. Thirdly, the ratio of phospholipids containing 5,8,11-eicosatrienoic acid, or Mead acid (MA), increased. Finally, the expression of stearoyl-CoA desaturase-1 (SCD-1) increased. As the increase of MA is seen as an index of polyunsaturated FA (PUFA) deficiency, and the expression of SCD-1 is suppressed by PUFA, these results strongly suggest that the loss of Reelin leads to PUFA deficiency. Hence, MUFA and MA are synthesized in response to this deficiency, in part by inducing SCD-1 expression. This is the first report of changes of FA composition in the reeler mouse brain and provides a basis for further investigating the new role of Reelin in the development and function of the brain.
AB - Reelin is a secreted protein essential for the development and function of the mammalian brain. The receptors for Reelin, apolipoprotein E receptor 2 and very low-density lipoprotein receptor, belong to the low-density lipoprotein receptor family, but it is not known whether Reelin is involved in the brain lipid metabolism. In the present study, we performed lipidomic analysis of the cerebral cortex of wild-type and Reelin-deficient (reeler) mice, and found that reeler mice exhibited several compositional changes in phospholipids. First, the ratio of phospholipids containing one saturated fatty acid (FA) and one docosahexaenoic acid (DHA) or arachidonic acid (ARA) decreased. Secondly, the ratio of phospholipids containing one monounsaturated FA (MUFA) and one DHA or ARA increased. Thirdly, the ratio of phospholipids containing 5,8,11-eicosatrienoic acid, or Mead acid (MA), increased. Finally, the expression of stearoyl-CoA desaturase-1 (SCD-1) increased. As the increase of MA is seen as an index of polyunsaturated FA (PUFA) deficiency, and the expression of SCD-1 is suppressed by PUFA, these results strongly suggest that the loss of Reelin leads to PUFA deficiency. Hence, MUFA and MA are synthesized in response to this deficiency, in part by inducing SCD-1 expression. This is the first report of changes of FA composition in the reeler mouse brain and provides a basis for further investigating the new role of Reelin in the development and function of the brain.
UR - http://www.scopus.com/inward/record.url?scp=85053712871&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053712871&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2018.09.089
DO - 10.1016/j.bbrc.2018.09.089
M3 - Article
C2 - 30241938
AN - SCOPUS:85053712871
SN - 0006-291X
VL - 505
SP - 81
EP - 86
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -