TY - JOUR
T1 - Three-Dimensional Imaging of Whole-Body Zebrafish Revealed Lipid Disorders Associated with Niemann-Pick Disease Type C1
AU - Liang, Xiaoping
AU - Cao, Shengxi
AU - Xie, Peisi
AU - Hu, Xudong
AU - Lin, Yusheng
AU - Liang, Jiehua
AU - Zhang, Shengqi
AU - Xian, Bai
AU - Cao, Hong
AU - Luan, Tiangang
AU - Cai, Zongwei
N1 - This work was supported by the National Key Research and Development Program of China (no. 2018YFD0900604), the National Natural Science Foundation of China (nos. 81402897 and 21625703), and the Talent Introduction Project of Guangdong University of Technology (no. 220413203).
Publisher Copyright:
© 2021 American Chemical Society
PY - 2021/6/15
Y1 - 2021/6/15
N2 - Imaging of lipids of whole-body specimens in two-dimensional (2D) analysis provides a global picture of the lipid changes in lipid-disturbed diseases, enabling a better understanding of lipid functions and lipid-modulation processes in different organs. However, 2D imaging of a single cross section can hardly characterize the whole-body lipid alterations. In this work, a three-dimensional matrix-assisted laser desorption/ionization mass spectrometry imaging (3D MALDI-MSI) approach was developed for analysis of whole-body zebrafish, for the first time, and applied to identify altered lipids and map their spatial distributions by using a zebrafish model of Niemann-Pick disease type C1 (NPC1), a neurovisceral lipid storage disorder causing both neurodegenerative disorder and visceral organ damage. The constructed 3D fish model provided comprehensive information on the 3D distribution of lipids of interest and allowed direct correlations between these lipids and organs of the fish. Obtained results revealed that several sphingolipids and phospholipids showed significant alterations and exhibited different localization patterns in various organs such as the brain, spinal cord, intestines, and liver-spleen region in thenpc1gene mutant fish compared to those of the wild type. The whole-body 3D MALDI-MSI approach revealed unique lipid signatures for different NPC1-affected organs, which might offer insights into the link between the impaired lipid storage and subsequent clinical symptoms, such as neurodegeneration and hepatosplenomegaly.
AB - Imaging of lipids of whole-body specimens in two-dimensional (2D) analysis provides a global picture of the lipid changes in lipid-disturbed diseases, enabling a better understanding of lipid functions and lipid-modulation processes in different organs. However, 2D imaging of a single cross section can hardly characterize the whole-body lipid alterations. In this work, a three-dimensional matrix-assisted laser desorption/ionization mass spectrometry imaging (3D MALDI-MSI) approach was developed for analysis of whole-body zebrafish, for the first time, and applied to identify altered lipids and map their spatial distributions by using a zebrafish model of Niemann-Pick disease type C1 (NPC1), a neurovisceral lipid storage disorder causing both neurodegenerative disorder and visceral organ damage. The constructed 3D fish model provided comprehensive information on the 3D distribution of lipids of interest and allowed direct correlations between these lipids and organs of the fish. Obtained results revealed that several sphingolipids and phospholipids showed significant alterations and exhibited different localization patterns in various organs such as the brain, spinal cord, intestines, and liver-spleen region in thenpc1gene mutant fish compared to those of the wild type. The whole-body 3D MALDI-MSI approach revealed unique lipid signatures for different NPC1-affected organs, which might offer insights into the link between the impaired lipid storage and subsequent clinical symptoms, such as neurodegeneration and hepatosplenomegaly.
UR - http://www.scopus.com/inward/record.url?scp=85108368255&partnerID=8YFLogxK
U2 - 10.1021/acs.analchem.1c00196
DO - 10.1021/acs.analchem.1c00196
M3 - Journal article
AN - SCOPUS:85108368255
SN - 0003-2700
VL - 93
SP - 8178
EP - 8187
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 23
ER -
