Lipidomic analysis of brain and hippocampus from mice fed with high-fat diet and treated with fecal microbiota transplantation

Abstract

Background: Dietary fat intake affects brain composition and function. Different types of dietary fatty acids alter species and abundance of brain lipids in mice. The aim of this study is to explore whether the changes are effective through gut microbiota.

Methods: In our study, 8-week-old male C57BL/6 mice were randomly divided into 7 groups and fed with high-fat diet (HFD) with different fatty acid compositions, control (CON) group, long-chain saturated fatty acid (LCSFA) group, medium-chain saturated fatty acid (MCSFA) group, n-3 polyunsaturated fatty acid (n-3 PUFA) group, n-6 polyunsaturated fatty acid (n-6 PUFA) group, monounsaturated fatty acid (MUFA) group and trans fatty acid (TFA) group. Then, the fecal microbiota transplant (FMT) was performed in other pseudo germ-free mice after antibiotic treatment. The experimental groups were orally perfused with gut microbiota that induced by HFD with different types of dietary fatty acids. The mice were fed with regular fodder before and after FMT. High-performance liquid chromatography-mass spectrometry (LC-MS) was used to analysis the composition of fatty acids in the brain of HFD-fed mice and hippocampus of mice treated with FMT which was collected from HFD-fed mice.

Results: The content of acyl-carnitines (AcCa) increased and lysophosphatidylgylcerol (LPG) decreased in all kinds of HFD groups. phosphatidic acids (PA), phosphatidylethanolamine (PE) and sphingomyelin (SM) contents were significantly increased in the n-6 PUFA-fed HFD group. The HFD elevated the saturation of brain fatty acyl (FA). Lysophosphatidylcholine (LPC), lysodi-methylphosphatidylethanolamine (LdMePE), monolysocardiolipin (MLCL), dihexosylceramides (Hex2Cer), and wax ester (WE) significantly increased after LCSFA-fed FMT. MLCL reduced and cardiolipin (CL) raised significantly after n-3 PUFA-fed FMT.

Conclusions: The study revealed, HFD and FMT in mice had certain effects on the content and composition of fatty acids in the brain, especially on glycerol phospholipid (GP). The change of AcCa content in FA was a good indicator of dietary fatty acid intake. By altering the fecal microbiota, dietary fatty acids might affect brain lipids.

Keywords: Brain lipid; Dietary fatty acid; FMT; High-fat diet; Lipidomics.

Fig. 1

Flow diagram of the study

Fig. 2

Relative abundance of GP in brain of mice fed with HFD. A–I: GP as a main class can be subdivided into classes: PE, MePC, BisMePA, PA, dMePE, DLCL, LPG, BiotinylPE and PS (Mean ± SD, n = 6). a: p < 0.05, compared to CON group; b: p < 0.05, compared to LCSFA group; c: p < 0.05, compared to MCSFA group; d: p < 0.05, compared to MUFA group; e: p < 0.05, compared to n-3 PUFA group; f: p < 0.05, compared to n-6 PUFA group. Mean ± SD, n = 6

Fig. 3

Relative abundance of the AcCa class in FA main class in brain of mice fed with HFD. a: p < 0.05, compared to CON group; b: p < 0.05, compared to LCSFA group; c: p < 0.05, compared to MCSFA group; d: p < 0.05, compared to MUFA group; e: p < 0.05, compared to n-3 PUFA group; f: p < 0.05, compared to n-6 PUFA group. Mean ± SD, n = 6

Fig. 4

Unsaturation degree of total FA in brain of mice fed with HFD. *, **, ***denotes a statistically significant difference (p < 0.05, 0.01, 0.001) compared to the CON group, the lipid contents were indicated in the figure in % (Mean ± SD, n = 6)

Fig. 5

The carbon atom numbers of FA in brain of mice fed with HFD. *, **, ***denotes a statistically significant difference (p < 0.05, 0.01, 0.001) compared to the CON group, the lipid contents were indicated in the figure in % (Mean ± SD, n = 6)

Fig. 6

Relative abundance of the ST and SM class in SP main class in brain of mice fed with HFD. a: p < 0.05, compared to CON group; b: p < 0.05, compared to LCSFA group; c: p < 0.05, compared to MCSFA group; d: p < 0.05, compared to MUFA group; e: p < 0.05, compared to n-3 PUFA group; f: p < 0.05, compared to n-6 PUFA group. Mean ± SD, n = 6

Fig. 7

Relative abundance of GP in brain of mice with FMT. A–G: GP as a main class can be subdivided into classes: cPA, CL, LPC, LPMe, LdMePE, MLCL and PEt. a: p < 0.05, compared to + CON-0 group; b: p < 0.05, compared to + CON-1 group; c: p < 0.05, compared to + CON group; d: p < 0.05, compared to + LCSFA group; e: p < 0.05, compared to + MCSFA group; f: p < 0.05, compared to + MUFA group; g: p < 0.05, compared to + n-3 PUFA group; h: p < 0.05, compared to + n-6 PUFA group. Mean ± SD, n = 3–5

Fig. 8

Relative abundance of WE class in FA main class in brain of mice with FMT. a: p < 0.05, compared to + CON-0 group; b: p < 0.05, compared to + CON-1 group; c: p < 0.05, compared to + CON group; d: p < 0.05, compared to + LCSFA group; e: p < 0.05, compared to + MCSFA group; f: p < 0.05, compared to + MUFA group; g: p < 0.05, compared to + n-3 PUFA group; h: p < 0.05, compared to + n-6 PUFA group. Mean ± SD, n = 3–5

Fig. 9

Relative abundance of SP in brain of mice with FMT. A, B: SP as a main class can be subdivided into classes: Hex2Cer and SM. a: p < 0.05, compared to + CON-0 group; b: p < 0.05, compared to + CON-1 group; c: p < 0.05, compared to + CON group; d: p < 0.05, compared to + LCSFA group; e: p < 0.05, compared to + MCSFA group; f: p < 0.05, compared to + MUFA group; g: p < 0.05, compared to + n-3 PUFA group; h: p < 0.05, compared to + n-6 PUFA group. Mean ± SD, n = 3–5