In this study, we focused on the phosphorylcholine-containing lipid effects after chronic PM2.5 exposure. However, the perturbations of other lipids are unknown.
Additionally, in some organs such as pancreas, the levels of lipidome difference between two groups in PLS-DA model was not consistent with those in Wilcoxon rank sum tests;
we speculate the univariate analysis was easily influenced by outlier sample, due to our small sample sizes (n). On the other hand, the lipid changes may occur in certain cell types of the organ; however, we are unable to confirm, due to an entire organ was used for analysis.
To our knowledge, this is the first study to examine the changes of phosphorylcholine-containing lipids in various organs and serum of rats after chronic exposure to low-dose PM2.5 by MS-based lipidomics. Although few researches
extrapulmonary organs, the underlying mechanisms is not clear. The results of this study provided the direction and foundation for future studies. In the future, further examination such as histopathological analysis focusing on the target organ—testis, and insulin resistance test on the pancreas will help us to clarify the potential important health effects of PM2.5 exposure on the male reproductive system and pancreas function.
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Figures
phosphocholine Phosphorylcholine-containing lipids Representative structures
Lyso-PCs
(Lyso-phosphatidylcholines)
Diacyl-PCs
(Diacyl-phosphatidylcholines)
O-PCs
(O-alkyl-acyl-PCs, Plasmanylcholines)
P-PCs
(O-alkenyl-acyl-PCs, Plasmenylcholines)
SMs
(Sphingomyelins)
Figure 1. Representative structures of various phosphorylcholine-containing lipids.
hydroxyl substituent
alkyl ether
alkenyl ether
Figure 2. Phosphorylcholine-containing lipids composition in each organ of rat. (A) Kidney (B) Pancreas (C) Testis (D) Spleen (E) Lung (F) Epididymis (G) Liver (H) Heart (I) Serum. a Number of identified lipids for each lipid subclass; b Percentage of identified lipids for each lipid subclass.
Lyso-PCs: lyso-phosphatidylcholines; Diacyl-PCs: diacyl-phosphatidylcholines; O-PCs: O-alkyl-acyl-PC (plasmanylcholines); P-PCs: O-alkenyl-acyl-PC (plasmenylcholines); Unknown-PCs: unknown-phosphatidylcholines; SMs: sphingomyelins.
A
b
B C D
E F G H
a
I
Figure 3. The PLS-DA score plots from the analysis of UPLC-MS/MS spectra of phosphorylcholine-containing lipids in each organ of rats after chronic ambient PM2.5 exposure. (A) Testis, R2Y: 0.962, Q2: 0.825 (B) Pancreas, R2Y: 0.972, Q2: 0.833 (C) Heart, R2Y: 0.933, Q2: 0.627 (D) Liver, R2Y: 0.955, Q2: 0.498 (E) Kidney, R2Y: 0.928, Q2: 0.272 (F) Serum, R2Y: 0.977, Q2: 0.885. Rad circle: exposure PM2.5 group; Green square: control group.
A B C
F
D E
Figure 4. Permutation test of PLS-DA model for phosphorylcholine-containing lipids in each organ of rats after chronic ambient PM2.5 exposure. (A) Testis (B) Pancreas (C) Heart (D) Liver (E) Kidney (F) Serum. 500 times permutation tests were used in the study. All groups accorded with the requirement of the standard. R2 presented on green circles and Q2 presented on blue boxes.
A B C
D E F
Tables
Table 1. Significant changed phosphorylcholine-containing lipids in the testis of rats after chronic ambient PM2.5 exposure.
a Variable Importance Projection of PLS-DA component 1; b Fold change calculated by the median peak area ratio of treatment group and control group; c All the features were qualified false discovery rate correction. * p-value < 0.05; ** p-value < 0.01.
Lyso-PCs: lyso-phosphatidylcholines; Diacyl-PCs: diacyl-phosphatidylcholines.
Subclass Lipid name VIP a Fold change b Wilcoxon rank sum
tests (p-value) c
Lyso-PCs
PC(16:1/0:0) + PC(0:0/16:1) 1.62 0.12 *
PC(20:4/0:0) 1.94 0.04 **
PC(0:0/18:1) 1.91 0.06 **
PC(20:2/0:0) 1.59 0.08 **
PC(22:5/0:0) 1.89 0.03 **
Diacyl-PCs
Saturated PC(16:0/16:0) 1.76 0.72 **
Monounsaturated PC(16:0/18:1) 1.54 0.95 *
Polyunsaturated
PC(22:5/18:0) 1.66 0.55 *
PC(18:2/20:4) 1.63 2.58 *
PC(16:0/22:6) 1.11 1.45 *
PC(34:4) 1.32 1.54 *
PC(38:2) 1.39 1.58 *
PC(42:6) 1.52 2.09 **
PC(42:4) 1.34 1.43 *
Table 1. Significant changed phosphorylcholine-containing lipids in the testis of rats after chronic ambient PM2.5 exposure. (continued)
a Variable Importance Projection of PLS-DA component 1; b Fold change calculated by the median peak area ratio of treatment group and control group; c All the features qualified false discovery rate correction. * p-value < 0.05; ** p-value < 0.01. P-PCs: O-alkenyl-acyl-PC (plasmenylcholines).
Subclass Lipid name VIPa Fold changeb Wilcoxon rank sum
tests (p-value) c
P-PCs PC(P-16:0/20:3) 1.69 0.66 *
Sphingomyelins
SM(d18:2/23:0) 1.37 2.01 *
SM(d18:2/16:0) 1.49 2.18 *
SM(d34:1) 1.29 0.42 *
Unknown
PC(509) 2.03 0.68 **
PC(597) 1.99 0.05 **
PC(599) 1.78 0.08 **
SM(862) 1.95 1.88 **
SM(878) 1.82 1.84 *
SM(888) 1.72 2.33 *
Table 2. Significant changed phosphorylcholine-containing lipids in the pancreas of rats after chronic ambient PM2.5 exposure.
aVariable Importance Projection of PLS-DA component 1; bFold change calculated by the median peak area ratio of treatment group and control group. * p-value < 0.05; ** p-value < 0.01. Lyso-PCs: lyso-phosphatidylcholines; Diacyl-PCs:
diacyl-phosphatidylcholines.
Subclass Lipid name VIPa Fold changeb Wilcoxon rank sum
tests (p-value)
Lyso-PCs PC(0:0/18:2) 2.49 1.55 *
Diacyl-PCs
PC(40:2) 1.32 1.24 *
PC(16:0/22:6) 2.50 0.67 *
PC(18:0/22:6) 2.62 0.74 *
PC(44:4) 1.99 0.46 *
Table 3. Significant changed phosphorylcholine-containing lipids in the heart, liver, and kidney of rats after chronic ambient PM2.5 exposure.
aVariable Importance Projection of PLS-DA component 1; bFold change calculated by the median peak area ratio of treatment group and control group. * p-value < 0.05; ** p-value < 0.01. Diacyl-PCs: diacyl-phosphatidylcholines; O-PC: O-alkyl-acyl-PCs
(Plasmanylcholines).
Organs Subclass Lipid name VIPa Fold changeb Wilcoxon rank sum
tests (p-value)
Heart Polyunsaturated diacyl-PCs PC(20:4/20:4) 2.83 1.23 *
O-PCs PC(O-18:0/16:0) 1.96 0.75 *
Liver Polyunsaturated diacyl-PCs PC(34:4) 2.50 0.53 *
Unknown PC(827) 1.31 0.77 *
Kidney
O-PCs PC(O-18:0/16:0) 1.66 0.64 *
Unknown
PC(843) 1.81 0.80 *
PC(863) 1.04 0.78 *
SM(872) 2.69 1.46 *
Table 4. Significant changed phosphorylcholine-containing lipids in the serum of rats after chronic ambient PM2.5 exposure.
a Variable Importance Projection of PLS-DA component 1; b Fold change calculated by the median peak area ratio of treatment group and control group; c Qualified false discovery rate correction. * p-value < 0.05; ** p-value < 0.01. Lyso-PCs:
lyso-phosphatidylcholines; Diacyl-PCs: diacyl-phosphatidylcholines.
Subclass Lipid name VIPa Fold changeb Wilcoxon rank sum
tests (p-value)
Lyso-PCs PC(18:0/0:0) 2.30 1.34 **
Diacyl-PCs
Monounsaturated
PC(16:0/16:1) 2.19 0.60 **
PC(16:0/17:1) 1.52 0.74 *
PC(16:0/18:1) 1.69 0.83 *
Polyunsaturated PC(16:0/20:4) 2.31 0.83 **
PC(22:5/20:3) 1.52 1.30 **
Unknown PC(843) 1.37 1.25 *
c
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