Brain N-Glycosylation and Lipidomic Profile Changes Induced by a High-Fat Diet in Dyslipidemic Hamsters

Abstract

The consumption of diets rich in saturated fats is known to be associated with higher mortality. The adoption of healthy habits, for instance adhering to a Mediterranean diet, has proved to exert a preventive effect towards cardiovascular diseases and dyslipidemia. Little is known about how a suboptimal diet can affect brain function, structure, and the mechanisms involved. The aims of this study were to examine how a high-fat diet can alter the brain N-glycan and lipid profile in male Golden Syrian hamsters and to evaluate the potential of a Mediterranean-like diet to reverse this situation. During twelve weeks, hamsters were fed a normal fat diet (CTRL group), a high-fat diet (HFD group), and a high-fat diet followed by a Mediterranean-like diet (MED group). Out of seventy-two identified N-glycans, fourteen were significant (p < 0.05) between HFD and CTRL groups, nine between MED and CTRL groups, and one between MED and HFD groups. Moreover, forty-nine lipids were altered between HFD and CTRL groups, seven between MED and CTRL groups, and five between MED and HFD groups. Our results suggest that brain N-glycan composition in high-fat diet-fed hamsters can produce events comparable to those found in some neurodegenerative diseases, and may promote brain ageing.

Keywords: N-glycan; brain glycosylation; dyslipidemia; high-fat diet; lipidomics; mass spectrometry; mediterranean diet.

Figure 1

Effect of the HFD and MED on liver histology of Golden Syrian hamsters. (A) Outline of the experimental design. (B) Steatosis score of histological changes in the liver. Differences were detected using Fisher’s exact test (* p-value < 0.05, ** p-value < 0.001). (C–E) Histological analysis of steatosis in liver sections stained with Hematoxylin and Eosin (400×). (F) Relative hepatic lipid content of hamsters in experimental groups. CTRL, normal diet; HFD, high-fat diet; MED, Mediterranean-like diet. Differences among groups in hepatic total lipid content were detected by Student t-test. All results were considered statistically significant at p-value < 0.05.

Figure 2

Representative chromatogram of the brain N-glycan profile representing selected statistically significant structures in the three groups (CTRL, HFD, and MED). (A) Pie chart depicting the degree of the 72 N-glycans identified in hamster brain tissue. Oligo, oligomannose; Bi, biantennary; Tri, triantennary; Tetra, tetrantennary. (B) Pie chart depicting the percentage of fucosylated and sialylated N-glycans in hamster brain tissue. Non-fuc/sial, non-fucosylated and non-sialylated N-glycans. Structural symbols for the N-glycans are shown below the chromatogram.

Figure 3

Boxplots showing increased and decreased abundance at week 12 for each statistically significant N-glycan (* p-value < 0.05, ** p-value < 0.01, *** p-value < 0.001).

Figure 3

Boxplots showing increased and decreased abundance at week 12 for each statistically significant N-glycan (* p-value < 0.05, ** p-value < 0.01, *** p-value < 0.001).