Fish Hydrolysate Supplementation Containing n-3 Long Chain Polyunsaturated Fatty Acids and Peptides Prevents LPS-Induced Neuroinflammation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals and Treatments
2.2. Quantitative Real Time PCR
2.3. Western Blot
2.4. Lipid Analysis
2.5. Oxylipin Quantification
2.6. Statistical Analysis
3. Results
3.1. Fish Hydrolysate Supplementation Decreases Proinflammatory Marker Expression and Prevents IκB Degradation in Response to LPS
3.2. Fish Hydrolysate Supplementation Modulates Microglial Activation Markers in Response to LPS
3.3. Fish Hydrolysate Supplementation Prevents LPS-Induced Changes in the Expression of Neurotrophins
3.4. Fish Hydrolysate and DHA Supplementations Affect Cortical Fatty Acid Composition
3.5. Fish Hydrolysate Supplementation Affects Hippocampal Oxylipin Concentration in LPS-Treated Animals
3.6. Multivariate Analysis Highlights the Separation of Oxylipin Profile in Function of the Supplementation in LPS-Treated Animals
3.7. LPS-Induced Hippocampal Expression of Oxylipin Biosynthesis Enzymes Is Regulated by Supplementations
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
5-oxoETE | 5-oxo-eicosatetraenoic acid |
AA | arachidonic acid |
ALA | α-linolenic acid |
Arg1 | arginase 1 |
BDNF | brain-derived neurotrophic factor |
CD | cluster of differentiation |
CNS | central nervous system |
COX | cyclooxygenase |
DHA | docosahexaenoic acid |
EET | epoxy eicosatrienoic acid |
EPA | eicosapentaenoic acid |
HDoHE | hydroxy-docosahexaenoic acid |
HETE | hydroxy-eicosatetraenoic acid |
HODE | hydroxy-octadecadienoic acid |
IL | interleukin |
iNOS | inducible nitric oxide synthase |
JNK | c-Jun N-terminal kinase |
LA | linoleic acid |
LC-PUFAs | long chain polyunsaturated fatty acids |
LOX | lipoxygenase |
LPS | lipopolysaccharide |
Lx | lipoxin |
MAPK | mitogen-activated protein kinase |
MaR | maresin |
MCP-1/CCL2 | monocyte chemoattractant protein-1 |
NF-κB | nuclear factor kappa B |
NGF | nerve growth factor |
NO | nitric oxide |
PG | prostaglandin |
PUFAs | polyunsaturated fatty acids |
SPMs | specialized proresolving mediators |
SOCS | Suppressor of cytokine signalling |
TGF | transforming growth factor |
TLR | toll-like receptor |
TNF | tumor necrosis factor |
Trk | tyrosine receptor kinase |
Tx | thromboxane |
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Control | Hydrolysate | DHA | |
---|---|---|---|
Water (µL/day) | 100 | - | 100 |
Peanut oil (µL/day) | 50 | 50 | - |
Fish hydrolysate group (µL/day) | - | 100 | - |
Peptides (mg/day) | - | 5 | - |
DHA (mg/day) | - | 0.143 | - |
DHA supplementation group (µL/day) | - | - | 50 |
DHA (mg/day) | - | - | 10 |
Fatty Acid (% of Total Fatty Acids) | Control | Hydrolysate | DHA | Statistical Effect | |||||
---|---|---|---|---|---|---|---|---|---|
Saline | LPS | Saline | LPS | Saline | LPS | Supplementation | LPS | Supplementation × LPS | |
14:0 | 0.13 ± 0.00 | 0.13 ± 0.00 | 0.12 ± 0.00 | 0.13 ± 0.00 | 0.13 ± 0.00 | 0.13 ± 0.00 | - | - | - |
15:0 | 0.04 ± 0.00 | 0.05 ± 0.00 | 0.05 ± 0.00 | 0.05 ± 0.00 | 0.05 ± 0.01 | 0.04 ± 0.00 | - | - | - |
16:0 | 21.43 ± 0.22 | 21.36 ± 0.31 | 21.36 ± 0.15 | 21.49 ± 0.12 | 21.27 ± 0.07 | 21.10 ± 0.15 | - | - | - |
17:0 | 0.14 ± 0.00 | 0.16 ± 0.01 | 0.14 ± 0.00 | 0.14 ± 0.00 | 0.16 ± 0.02 | 0.14 ± 0.00 | - | - | - |
18:0 | 20.03 ± 0.06 a | 19.65 ± 0.04 b | 20.06 ± 0.08 a | 19.66 ± 0.17 b | 19.74 ± 0.05 b | 19.78 ± 0.09 b | - | p = 0.0001 | p = 0.0034 |
20:0 | 0.22 ± 0.01 | 0.21 ± 0.01 | 0.21 ± 0.01 | 0.21 ±0.01 | 0.22 ± 0.01 | 0.23 ± 0.01 | - | - | - |
22:0 | 0.15 ± 0.01 | 0.17 ± 0.02 | 0.16 ± 0.01 | 0.15 ± 0.01 | 0.15 ± 0.01 | 0.16 ± 0.00 | - | - | - |
24:0 | 0.17 ± 0.01 | 0.17 ± 0.01 | 0.17 ± 0.01 | 0.17 ± 0.00 | 0.17 ± 0.01 | 0.18 ± 0.01 | - | - | - |
SFAs | 42.31 ± 0.21 | 41.89 ± 0.32 | 42.27 ± 0.19 | 42.00 ± 0.15 | 41.89 ± 0.08 | 41.76 ± 0.20 | - | - | - |
16:1n-9 | 0.15 ± 0.00 | 0.16 ± 0.00 | 0.16 ± 0.00 | 0.16 ± 0.00 | 0.15 ± 0.00 | 0.15 ± 0.00 | p = 0.0047 | - | - |
16:1n-7 | 0.51 ± 0.01 | 0.53 ± 0.01 | 0.52 ± 0.00 | 0.53 ± 0.01 | 0.52 ± 0.01 | 0.52 ± 0.01 | - | - | - |
18:1t | 0.03 ± 0.00 a | 0.03 ± 0.00 a | 0.04 ± 0.00 a | 0.04 ± 0.01 a | 0.04 ± 0.01 a | 0.07 ± 0.00 b | p = 0.0004 | - | p = 0.0114 |
18:1n-9 | 14.04 ± 0.11 | 14.17 ± 0.11 | 14.17 ± 0.11 | 14.12 ± 0.10 | 14.22 ± 0.18 | 14.42 ± 0.11 | - | - | - |
18:1n-7 | 3.51 ± 0.01 | 3.55 ± 0.04 | 3.53 ± 0.02 | 3.50 ± 0.02 | 3.49 ± 0.03 | 3.49 ± 0.01 | - | - | - |
20:1n-9 | 0.90 ± 0.03 | 0.94 ± 0.04 | 0.90 ± 0.03 | 0.90 ± 0.03 | 0.93 ± 0.06 | 0.96 ± 0.03 | - | - | - |
20:1n-7 | 0.24 ± 0.01 | 0.26 ± 0.01 | 0.25 ± 0.01 | 0.24 ± 0.01 | 0.26 ± 0.02 | 0.26 ± 0.01 | - | - | - |
22:1n-9 | 0.09 ± 0.01 | 0.11 ± 0.01 | 0.09 ± 0.00 | 0.10 ± 0.00 | 0.10 ± 0.01 | 0.10 ± 0.00 | - | - | - |
24:1n-9 | 0.20 ± 0.01 a,b,c | 0.18 ± 0.01 b,e | 0.22 ± 0.01 a,d | 0.20 ± 0.01 b,d,e | 0.20 ± 0.01 a,e | 0.23 ± 0.01 c,d | - | - | p = 0.0473 |
MUFAs | 19.68 ± 0.15 | 19.93 ± 0.18 | 19.86 ± 0.16 | 19.79 ± 0.15 | 19.90 ± 0.28 | 20.19 ± 0.14 | - | - | - |
18:2n-6 | 0.52 ± 0.01 | 0.47 ± 0.02 | 0.51 ± 0.01 | 0.52 ± 0.01 | 0.54 ± 0.01 | 0.52 ± 0.01 | - | - | - |
20:2n-6 | 0.13 ± 0.00 a | 0.12 ± 0.00 b | 0.12 ± 0.00 b,c | 0.13 ± 0.00 a,b | 0.13 ± 0.00 a | 0.13 ± 0.00 a,c | - | p = 0.0432 | p = 0.0089 |
20:3n-6 | 0.41 ± 0.01 | 0.39 ± 0.01 | 0.42 ± 0.00 | 0.42 ± 0.01 | 0.47 ± 0.01 | 0.46 ± 0.01 | p < 0.0001 | - | - |
20:4n-6 | 9.98 ± 0.11 | 10.15 ± 0.08 | 9.96 ± 0.09 | 9.95 ± 0.06 | 9.34 ± 0.16 | 9.43 ± 0.09 | p < 0.0001 | - | - |
22:4n-6 | 2.05 ± 0.03 | 2.17 ± 0.07 | 2.05 ± 0.02 | 2.14 ± 0.04 | 1.93 ± 0.04 | 2.02 ± 0.04 | p = 0.0069 | p = 0.0218 | - |
22:5n-6 | 0.30 ± 0.01 | 0.32 ± 0.02 | 0.29 ± 0.01 | 0.30 ± 0.01 | 0.28 ± 0.02 | 0.27 ± 0.00 | p = 0.0001 | - | - |
n-6 | 13.41 ± 0.13 | 13.61 ± 0.16 | 13.34 ± 0.08 | 13.45 ± 0.07 | 12.69 ± 0.19 | 12.81 ± 0.13 | p < 0.0001 | - | - |
20:5n-3 | 0.06 ± 0.01 | 0.06 ± 0.00 | 0.06 ± 0.00 | 0.06 ± 0.00 | 0.08 ± 0.00 | 0.08 ± 0.00 | p < 0.0001 | - | - |
22:5n-3 | 0.13 ± 0.00 | 0.14 ± 0.00 | 0.14 ± 0.00 | 0.14 ± 0.00 | 0.17 ± 0.00 | 0.17 ± 0.00 | p < 0.0001 | - | - |
22:6n-3 | 15.85 ± 0.29 | 15.67 ± 0.25 | 15.69 ± 0.24 | 16.09 ± 0.24 | 16.74 ± 0.28 | 16.19 ± 0.18 | p = 0.0175 | - | - |
n-3 | 16.05 ± 0.29 | 15.87 ± 0.24 | 15.89 ± 0.24 | 16.29 ± 0.24 | 16.99 ± 0.28 | 16.43 ± 0.18 | p = 0.01 | - | - |
20:3n-9 | 0.13 ± 0.02 a,b | 0.09 ± 0.01 c,d | 0.17 ± 0.03 a | 0.08 ± 0.00 c,d | 0.10 ± 0.00 b,c | 0.12 ± 0.01 b,d | - | p = 0.0066 | p = 0.0122 |
PUFAs | 29.59 ± 0.31 | 29.56 ± 0.28 | 29.40 ± 0.26 | 29.81 ± 0.20 | 29.78 ± 0.38 | 29.36 ± 0.13 | - | - | - |
dma16:0 | 2.23 ± 0.03 | 2.36 ± 0.03 | 2.27 ± 0.03 | 2.27 ± 0.05 | 2.24 ± 0.05 | 2.28 ± 0.02 | - | - | - |
dma18:0 | 3.99 ± 0.03 | 3.99 ± 0.03 | 3.98 ± 0.03 | 3.92 ± 0.03 | 3.97 ± 0.05 | 4.04 ± 0.03 | p = 0.0448 | - | - |
dma18:1n-9 | 1.19 ± 0.02 | 1.22 ± 0.03 | 1.20 ± 0.03 | 1.19 ± 0.02 | 1.19 ± 0.03 | 1.24 ± 0.02 | - | - | - |
dma18:1n-7 | 1.02 ± 0.02 | 1.05 ± 0.03 | 1.03 ± 0.02 | 1.03 ± 0.03 | 1.04 ± 0.03 | 1.08 ± 0.02 | - | - | - |
DMA | 8.43 ± 0.08 | 8.62 ± 0.08 | 8.48 ± 0.06 | 8.41 ± 0.13 | 8.43 ± 0.15 | 8.64 ± 0.09 | - | - | - |
n-6/n-3 | 0.84 ± 0.02 | 0.86 ± 0.02 | 0.84 ± 0.01 | 0.83 ± 0.01 | 0.75 ± 0.01 | 0.78 ± 0.01 | p < 0.0001 | - | - |
Oxylipin (pg /mg protein) | Control | Hydrolysate | DHA | Statistical Effect | |||||
---|---|---|---|---|---|---|---|---|---|
Saline | LPS | Saline | LPS | Saline | LPS | Supplementation | LPS | Supplementation × LPS | |
AA-oxylipins | |||||||||
Thromboxanes, prostaglandins | |||||||||
TxB2 | 1584.36 ± 136.93 | 1739.60 ± 138.94 | 1729.72 ± 220.19 | 1495.16 ± 30.78 | 1781.36 ± 166.54 | 1747.47 ± 205.07 | - | - | - |
6kPGF1α | 151.68 ± 68.79 a | 505.96 ± 66.67 b | 246.65 ± 83.26 a | 78.59 ± 49.27 a | 210.93 ± 69.00 a | 226.75 ± 92.39 a | - | - | p = 0.0086 |
PGF2α | 4429.79 ± 380.97 | 5550.45 ± 330.52 | 4582.04 ± 486.14 | 5708.87 ± 577.25 | 5656.33 ± 461.46 | 5155.75 ± 727.26 | - | - | - |
PGE2 | 1428.02 ± 141.17 a | 2366.55 ± 121.53 b | 1410.87 ± 117.93 a | 2356.64 ± 224.38 b | 1883.66 ± 204.02 a,b | 1881.02 ± 257.90 a,b | - | p = 0.0003 | p = 0.0211 |
PGD2 | 1741.08 ± 319.14 a | 3208.60 ± 445.99 b | 1639.05 ± 216.33 a | 3188.42 ± 282.95 b,c | 2301.83 ± 244.21 a,b | 2178.11 ± 411.06 a,c | - | p = 0.002 | p = 0.0314 |
PGA1 | 0.00 ± 0.00 a | 28.65 ± 7.78 b | 0.00 ± 0.00 a | 34.75 ± 11.80 b | 0.00 ± 0.00 a | 0.00 ± 0.00 a | p = 0.0014 | p < 0.0001 | p = 0.0014 |
15dPGJ2 | 31.15 ± 19.37 | 71.23 ± 8.44 | 13.59 ± 13.59 | 89.69 ± 19.08 | 45.69 ± 23.73 | 53.66 ± 24.59 | - | p = 0.0145 | - |
8isoPGA2 | 464.81 ± 24.87 | 651.95 ± 76.86 | 500.41 ± 109.57 | 864.62 ± 133.33 | 682.20 ± 116.56 | 750.64 ± 92.68 | - | p = 0.0184 | - |
Lipoxins | |||||||||
LxA4 | 265.31 ± 31.85 a | 764.10 ± 117.00 c | 352.61 ± 37.66 a,b | 1126.31 ± 115.00 d | 631.05 ± 121.16 b,c | 614.25 ± 151.20 b,c | - | p < 0.0001 | p = 0.0041 |
LxB4 | 119.60 ± 79.81 | 413.04 ± 100.91 | 488.09 ± 79.65 | 560.64 ± 67.12 | 342.60 ± 115.89 | 309.99 ± 112.83 | p = 0.0483 | - | - |
Epoxy fatty acids | |||||||||
14,15-EET | 258.15 ± 55.32 | 218.68 ± 27.43 | 221.62 ± 44.03 | 339.82 ± 95.94 | 317.46 ± 68.49 | 321.12 ± 36.59 | - | - | - |
8,9-EET | 665.74 ± 86.14 | 717.35 ± 62.99 | 745.55 ± 88.82 | 1132.12 ± 251.53 | 984.20 ± 127.64 | 904.92 ± 119.39 | - | - | - |
5,6-EET | 510.40 ± 59.39 | 552.36 ± 22.88 | 607.26 ± 61.65 | 776.15 ± 152.98 | 730.88 ± 94.28 | 687.14 ± 90.15 | - | - | - |
Hydroxy fatty acids | |||||||||
15-HETE | 5381.63 ± 491.85 a | 10236.55 ± 1133.60 b,c | 4986.08 ± 394. 85 a | 12370.92 ± 946.68 c | 8412.97 ± 1033.41 b | 8271.61 ± 1124.26 b | - | p < 0.0001 | p = 0.0014 |
8-HETE | 616.39 ± 59.62 a | 861.88 ± 71.18 b | 536.21 ± 32.63 a | 1094.93 ± 100.61 c | 825.45 ± 81.77 b | 823.81 ± 84.78 b | - | p = 0.0001 | p = 0.0033 |
12-HETE | 1496.97 ± 53.35 a,b | 2662.28 ± 394.98 c,d | 1188.01 ± 51.49 a | 3479.62 ± 252.58 d | 2076.89 ± 258.48 b,c | 2145.92 ± 439.72 b,c | - | p < 0.0001 | p = 0.0044 |
5-HETE | 5518.82 ± 671.54 | 6747.00 ± 403.13 | 5484.87 ± 486.33 | 8002.11 ± 382.00 | 7715.60 ± 1005.41 | 8939.82 ± 1212.00 | p = 0.0318 | p = 0.0262 | - |
5-oxoETE | 5524.57 ± 639.67 a | 6300.15 ± 474.39 a,c | 5286.41 ± 199.95 a | 9143.13 ± 785.06 b | 8623.43 ± 291.86 b | 7449.52 ± 981.74 b,c | p = 0.0072 | p = 0.0342 | p = 0.0022 |
LA-oxylipins | |||||||||
Hydroxy fatty acids | |||||||||
13-HODE | 1294.54 ± 41.33 a | 2091.36 ± 184.04 a | 1429.20 ± 192.49 a | 3655.32 ± 871.76 b | 2266.32 ± 315.64 a | 2212.73 ± 339.80 a | - | p = 0.0026 | p = 0.0134 |
9-HODE | 497.38 ± 19.99 a | 979.03 ± 109.81 b,c | 577.19 ± 76.69 a,b | 1628.82 ± 355.30 d | 967.76 ± 132.13 b,c | 950.78 ± 147.61 a,c | - | p = 0.0005 | p = 0.0066 |
DHA-oxylipins | |||||||||
Hydroxy fatty acids | |||||||||
17-HDoHE | 1208.83 ± 91.11 a,b | 2030.94 ± 216.72 c,d | 1002.70 ± 83.64 b | 2428.07 ± 154.48 c | 1717.12 ± 318.00 a,d | 1731.76 ± 194.06 a,d | - | p = 0.0001 | p = 0.0076 |
14-HDoHE | 819.92 ± 71.54 a,b | 1171.61 ± 168.81 b,c | 639.76 ± 45.18 a | 1683.52 ± 143.81 d | 1266.36 ± 167.27 c,d | 1290.20 ± 175.01 c,d | - | p = 0.0004 | p = 0.0056 |
7-MaR1 | 0.00 ± 0.00 a,b | 42.73 ± 11.82 b | 0.00 ± 0.00 a | 88.89 ± 50.81 c | 0.00 ± 0.00a | 0.00 ± 0.00a | p = 0.0289 | p = 0.0019 | p = 0.0289 |
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Chataigner, M.; Martin, M.; Lucas, C.; Pallet, V.; Layé, S.; Mehaignerie, A.; Bouvret, E.; Dinel, A.-L.; Joffre, C. Fish Hydrolysate Supplementation Containing n-3 Long Chain Polyunsaturated Fatty Acids and Peptides Prevents LPS-Induced Neuroinflammation. Nutrients 2021, 13, 824. https://doi.org/10.3390/nu13030824
Chataigner M, Martin M, Lucas C, Pallet V, Layé S, Mehaignerie A, Bouvret E, Dinel A-L, Joffre C. Fish Hydrolysate Supplementation Containing n-3 Long Chain Polyunsaturated Fatty Acids and Peptides Prevents LPS-Induced Neuroinflammation. Nutrients. 2021; 13(3):824. https://doi.org/10.3390/nu13030824
Chicago/Turabian StyleChataigner, Mathilde, Marie Martin, Céline Lucas, Veronique Pallet, Sophie Layé, Alexis Mehaignerie, Elodie Bouvret, Anne-Laure Dinel, and Corinne Joffre. 2021. "Fish Hydrolysate Supplementation Containing n-3 Long Chain Polyunsaturated Fatty Acids and Peptides Prevents LPS-Induced Neuroinflammation" Nutrients 13, no. 3: 824. https://doi.org/10.3390/nu13030824
APA StyleChataigner, M., Martin, M., Lucas, C., Pallet, V., Layé, S., Mehaignerie, A., Bouvret, E., Dinel, A.-L., & Joffre, C. (2021). Fish Hydrolysate Supplementation Containing n-3 Long Chain Polyunsaturated Fatty Acids and Peptides Prevents LPS-Induced Neuroinflammation. Nutrients, 13(3), 824. https://doi.org/10.3390/nu13030824