Highlights
- •Consumption of a high sucrose diet alters the brain free oxylipin profile.
- •The oxylipins changed by a high sucrose diet differ between sexes.
- •Regardless of diet, there are sex differences in the brain free oxylipin profile.
Abstract
Background
Methods
Results
Conclusion
Keywords
1. Introduction
- Caligiuri S.P.B.
- Parikh M.
- Stamenkovic A.
- Pierce G.N.
- Aukema H.M.
- Shinto L.
- Lahna D.
- Murchison C.F.
- Dodge H.
- Hagen K.
- David J.
- Kaye J.
- Quinn J.F.
- Wall R.
- Silbert L.C.
- Borkowski K.
- Pedersen T.L.
- Seyfried N.T.
- Lah J.J.
- Levey A.I.
- Hales C.M.
- Dammer E.B.
- Blach C.
- Louie G.
- Kaddurah-Daouk R.
- Newman J.W.
- Caligiuri S.P.B.
- Parikh M.
- Stamenkovic A.
- Pierce G.N.
- Aukema H.M.
- Devassy J.G.
- Yamaguchi T.
- Monirujjaman M.
- Gabbs M.
- Ravandi A.
- Zhou J.
- Aukema H.M.
- Gart E.
- Salic K.
- Morrison M.C.
- Caspers M.
- van Duyvenvoorde W.
- Heijnk M.
- Giera M.
- Bobeldijk-Pastorova I.
- Keijer J.
- Storsve A.B.
- Hals P.-A.
- Kleemann R.
- Norman J.E.
- Aung H.H.
- Otoki Y.
- Zhang Z.
- Taha A.Y.
- Rutledge J.C.
- Taha A.Y.
- Hennebelle M.
- Yang J.
- Zamora D.
- Rapoport S.I.
- Hammock B.D.
- Ramsden C.E.
- Ramsden C.E.
- Hennebelle M.
- Schuster S.
- Keyes G.S.
- Johnson C.D.
- Kirpich I.A.
- Dahlen J.E.
- Horowitz M.S.
- Zamora D.
- Feldstein A.E.
- McClain C.J.
- Muhlhausler B.S.
- Makrides M.
- Gibson R.A.
- Taha A.Y.
- Saikrishna K.
- Kumari R.
- Chaitanya K.
- Biswas S.
- Nayak P.G.
- Mudgal J.
- Kishore A.
- Nandakumar K.
- Devassy J.G.
- Yamaguchi T.
- Monirujjaman M.
- Gabbs M.
- Ravandi A.
- Zhou J.
- Aukema H.M.
- Monirujjaman M.
- Devassy J.G.
- Yamaguchi T.
- Sidhu N.
- Kugita M.
- Gabbs M.
- Nagao S.
- Zhou J.
- Ravandi A.
- Aukema H.M.
2. Methods
2.1 Animals and diets
The ARRIVE guidelines 2.0, ARRIVE Guidelines. (n.d.). https://arriveguidelines.org/arrive-guidelines (accessed August 29, 2022).
- Rutkowsky J.M.
- Lee L.L.
- Puchowicz M.
- Golub M.S.
- Befroy D.E.
- Wilson D.W.
- Anderson S.
- Cline G.
- Bini J.
- Borkowski K.
- Knotts T.A.
- Rutledge J.C.
Diet | Fat (%kcal) | Protein (%kcal) | Carbohydrate (%kcal) | Sucrose (g/kg) | Cornstarch (g/kg) |
---|---|---|---|---|---|
LSD | 13 | 19.1 | 67.9 | 120 | 432.99 |
HSD | 12.6 | 18.7 | 68.7 | 341 | 211.99 |
2.2 Serum glucose and insulin analyses
2.3 Free oxylipin extraction from brain
2.4 Mass spectrometry analysis of oxylipins
2.5 Statistical analysis
MetaboAnalyst, (n.d.). https://www.metaboanalyst.ca/MetaboAnalyst/ModuleView.xhtml (accessed August 25, 2021).
3. Results
3.1 The effects of a HSD and LSD on brain oxylipins in male mice


3.2 The effects of a HSD and LSD on brain oxylipins in female mice


3.3 Hierarchical clustering and analysis of sex effects on the brain oxylipin profiles and response to diet





Sex | Male | Female | ||
---|---|---|---|---|
Diet | LSD | HSD | LSD | HSD |
Linoleic acid derived oxylipins | ||||
Lipoxygenase products | ||||
9-HODE | 4.775 (0.275) | 2.603 (1.584) | 3.103 (1.721) | 1.515 (1.285) |
13-HODE | 7.368 (1.987) | 2.820 (3.717) | 5.172 (1.900) | 2.593 (1.720) |
9-oxo-ODE | 0.978 (0.208) | 0.385 (0.599) | 0.003 (0.162) | 0.535 (0.931) |
9,10,13-TriHOME | 0.940 (0.152) | 0.630 (0.308) | 0.460 (0.237) | 0.350 (0.300) |
9,12,13-TriHOME | 1.405 (0.464) | 0.929 (0.634) | 0.695 (0.635) | 0.414 (0.233) |
Cytochrome P450 products | ||||
9(10)-EpOME | 0.100 (0.182) | 0.622 (1.325) | 0.165 (1.171) | 0.012 (0.046) |
12(13)-EpOME | 0.481 (2.806) | 0.944 (1.243) | 2.643 (2.747) | 0.388 (1.130) |
9,10-DiHOME | 0.377 (0.136) | 0.417 (0.455) | 0.006 (0.037) | 0.006 (0.000) |
12,13-DiHOME | 0.759 (0.558) | 0.348 (0.429) | 0.251 (0.329) | 0.269 (0.425) |
Dihomo-γ-linolenic acid derived oxylipins | ||||
Lipoxygenase products | ||||
15(S)-HETrE | 2.807 (0.801) | 2.462 (0.851) | 1.288 (0.794) | 1.678 (1.442) |
Cyclooxygenase products | ||||
PGD/E1 | 1.898 (0.495) | 2.180 (0.119) | 1.625 (0.411) | 1.064 (0.285), |
Arachidonic acid derived oxylipins | ||||
Non-enzymatic | ||||
9-HETE | 91.157 (10.252) | 89.999 (15.108) | 198.919 (75.763) | 160.388 (49.810) |
Lipoxygenase products | ||||
8-HETE | 10.353 (3.727) | 11.116 (2.973) | 11.331 (2.051) | 15.661 (4.729) |
5-HETE | 14.459 (1.505) | 11.326 (4.283) | 12.517 (3.055) | 10.645 (5.160) |
11-HETE | 91.283 (10.369) | 90.098 (15.162) | 198.871 (76.009) | 160.436 (49.949) |
12-HETE | 100.504 (60.291) | 106.693 (26.330) | 52.045 (26.647) | 52.103 (33.257) |
15-HETE | 104.504 (8.101) | 120.780 (20.092) | 260.897 (35.824) | 226.901 (89.966) |
5-oxo-ETE | 4.113 (2.871) | 2.643 (3.734) | 4.120 (2.053) | 2.832 (3.849) |
12-oxo-ETE | 1.174 (0.373) | 1.845 (0.957) | 0.988 (0.520) | 1.258 (1.153) |
15-oxo-ETE | 5.985 (3.147) | 2.820 (0.513) | 7.117 (3.964) | 15.887 (9.614) |
5,15-DiHETE | 2.307 (0.494) | 2.757 (1.285) | 2.388 (1.144) | 1.956 (0.423) |
8,15-DiHETE | 58.707 (11.712) | 30.881 (11.588) | 33.712 (32.395) | 20.591 (1.756) |
LTB4 | 0.587 (0.253) | 0.246 (0.079) | 0.263 (0.045) | 0.227 (0.080) |
LTD4 | 0.085 (0.176) | 0.066 (0.117) | 0.001 (0.000) | 0.001 (0.000) |
6-trans-LTB4 | 0.393 (0.462) | 0.032 (0.051) | 0.004 (0.278) | 0.004 (0.018) |
Cyclooxygenase products | ||||
PGD2 | 253.530 (85.033) | 315.903 (5.885) | 266.072 (65.440) | 182.586 (44.286), |
PGE2 | 47.609 (20.925) | 51.192 (6.883) | 46.971 (28.662) | 29.114 (4.261), |
PGF2a | 74.048 (17.837) | 79.351 (6.582) | 86.942 (15.597) | 55.641 (6.288), |
PGJ2 | 1.565 (0.727) | 2.159 (0.244) | 2.243 (0.894) | 0.676 (0.352), |
15-deoxy-PGJ2 | 0.566 (0.231) | 0.673 (0.268) | 0.744 (0.514) | 0.412 (0.198) |
6-keto-PGF1a | 70.623 (23.335) | 58.411 (15.504) | 51.995 (18.767) | 42.614 (11.666) |
TXB2 | 61.604 (12.347) | 64.275 (9.773) | 72.375 (20.592) | 48.588 (3.849), |
Cytochrome P450 products | ||||
5(6)-EpETrE | 21.134 (11.172) | 21.893 (1.349) | 24.105 (10.127) | 30.866 (20.630) |
8(9)-EpETrE | 21.368 (8.369) | 21.365 (3.488) | 23.656 (7.610) | 21.446 (10.357) |
11(12)-EpETrE | 19.129 (8.212) | 19.314 (3.742) | 21.527 (7.591) | 19.062 (9.988) |
14(15)-EpETrE | 23.054 (6.692) | 25.247 (10.502) | 25.643 (7.719) | 16.308 (2.540) |
5,6-DiHETrE | 0.079 (0.086) | 0.003 (0.014) | 0.003 (0.050) | 0.003 (0.030) |
11,12-DiHETrE | 0.435 (0.171) | 0.277 (0.152) | 0.335 (0.263) | 0.298 (0.187) |
14,15-DiHETrE | 1.129 (0.161) | 0.943 (0.153) | 1.281 (0.674) | 0.951 (0.179) |
α-linolenic acid derived oxylipins | ||||
Lipoxygenase products | ||||
9-HOTrE | 1.696 (0.401) | 1.080 (1.183) | 0.013 (0.259) | 0.013 (0.000) |
13-HOTrE | 1.445 (0.266) | 0.880 (0.512) | 0.731 (0.810) | 0.656 (0.387) |
Eicosapentaenoic acid derived oxylipins | ||||
Lipoxygenase products | ||||
5-HEPE | 0.173 (0.240) | 0.065 (0.160) | 0.059 (0.561) | 0.008 (0.000) |
12-HEPE | 0.607 (0.453) | 0.469 (0.252) | 0.404 (0.171) | 0.027 (0.000), |
Cyclooxygenase products | ||||
PGD3 | 0.555 (0.301) | 0.447 (0.123) | 0.472 (0.127) | 0.298 (0.270) |
Cytochrome P450 products | ||||
5,6-DiHETE | 8.906 (4.868) | 6.145 (2.040) | 6.647 (4.994) | 5.155 (0.875) |
17,18-DiHETE | 4.557 (2.764) | 1.455 (2.751) | 3.902 (3.718) | 0.455 (3.287) |
Docosahexaenoic acid derived oxylipins | ||||
Cytochrome P450 products | ||||
7(8)-EpDPE | 2.676 (4.341) | 1.949 (2.608) | 2.697 (1.755) | 9.486 (9.969) |
10(11)-EpDPE | 1.227 (1.489) | 1.412 (0.149) | 2.914 (1.761) | 7.826 (9.095) |
13(14)-EpDPE | 2.480 (0.868) | 3.853 (1.099) | 3.365 (1.183) | 5.285 (11.738) |
16(17)-EpDPE | 2.599 (1.546) | 0.686 (0.730) | 1.973 (2.208) | 4.486 (10.677) |
19(20)-EpDPE | 4.864 (1.827) | 4.622 (0.611) | 6.221 (4.129) | 10.164 (11.956) |
16,17-DiHDPA | 0.189 (0.104) | 0.182 (0.103) | 0.203 (0.113) | 0.154 (0.157) |
19,20-DiHDPA | 0.913 (0.311) | 0.937 (0.193) | 1.280 (0.422) | 0.976 (0.112) |
4. Discussion
- Caligiuri S.P.B.
- Parikh M.
- Stamenkovic A.
- Pierce G.N.
- Aukema H.M.
- Caligiuri S.P.B.
- Parikh M.
- Stamenkovic A.
- Pierce G.N.
- Aukema H.M.
4.1 Effect of a high sucrose diet on the brain's oxylipin profile in males and females
- Tajima Y.
- Ishikawa M.
- Maekawa K.
- Murayama M.
- Senoo Y.
- Nishimaki-Mogami T.
- Nakanishi H.
- Ikeda K.
- Arita M.
- Taguchi R.
- Okuno A.
- Mikawa R.
- Niida S.
- Takikawa O.
- Saito Y.
- Shinto L.
- Lahna D.
- Murchison C.F.
- Dodge H.
- Hagen K.
- David J.
- Kaye J.
- Quinn J.F.
- Wall R.
- Silbert L.C.
- Borkowski K.
- Pedersen T.L.
- Seyfried N.T.
- Lah J.J.
- Levey A.I.
- Hales C.M.
- Dammer E.B.
- Blach C.
- Louie G.
- Kaddurah-Daouk R.
- Newman J.W.
- Tajima Y.
- Ishikawa M.
- Maekawa K.
- Murayama M.
- Senoo Y.
- Nishimaki-Mogami T.
- Nakanishi H.
- Ikeda K.
- Arita M.
- Taguchi R.
- Okuno A.
- Mikawa R.
- Niida S.
- Takikawa O.
- Saito Y.
- Borkowski K.
- Pedersen T.L.
- Seyfried N.T.
- Lah J.J.
- Levey A.I.
- Hales C.M.
- Dammer E.B.
- Blach C.
- Louie G.
- Kaddurah-Daouk R.
- Newman J.W.
- Do K.V.
- Hjorth E.
- Wang Y.
- Jun B.
- Kautzmann M.-A.I.
- Ohshima M.
- Eriksdotter M.
- Schultzberg M.
- Bazan N.G.
4.2 Potential mechanisms of HSD induced changes in the brain oxylipin profile
- Molee W.
- Bouillier-Oudot M.
- Auvergne A.
- Babilé R.
4.3 Sex as an important modifier of the brain oxylipin response to a HSD
4.4 Sex effects on the oxylipin profile and potential mechanisms
- Tajima Y.
- Ishikawa M.
- Maekawa K.
- Murayama M.
- Senoo Y.
- Nishimaki-Mogami T.
- Nakanishi H.
- Ikeda K.
- Arita M.
- Taguchi R.
- Okuno A.
- Mikawa R.
- Niida S.
- Takikawa O.
- Saito Y.
- Gerges S.H.
- El-Kadi A.O.S.
- Gerges S.H.
- El-Kadi A.O.S.
4.5 Study limitations and research gaps
- Taha A.Y.
- Hennebelle M.
- Yang J.
- Zamora D.
- Rapoport S.I.
- Hammock B.D.
- Ramsden C.E.
Funding
CRediT authorship contribution statement
Declaration of Competing Interest
Acknowledgments
Appendix. Supplementary materials
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