A diet enriched in docosahexanoic Acid exacerbates brain parenchymal extravasation of apo B lipoproteins induced by chronic ingestion of saturated fats

Abstract

Chronic ingestion of saturated fatty acids (SFAs) was previously shown to compromise blood-brain barrier integrity, leading to brain parenchymal extravasation of apolipoprotein B (apo B) lipoproteins enriched in amyloid beta. In contrast, diets enriched in mono- or polyunsaturated (PUFA) oils had no detrimental effect. Rather, n3 and n6 oils generally confer protection via suppression of inflammation. This study investigated in wild-type mice if a PUFA diet enriched in docosahexanoic acid (DHA) restored blood-brain barrier integrity and attenuated parenchymal apo B abundance induced by chronic ingestion of SFA. Cerebrovascular leakage of apo B was quantitated utilising immunofluorescent staining. The plasma concentration of brain-derived S100β was measured as a marker of cerebrovascular inflammation. In mice fed SFA for 3 months, provision thereafter of a DHA-enriched diet exacerbated parenchymal apo B retention, concomitant with a significant increase in plasma cholesterol. In contrast, provision of a low-fat diet following chronic SFA feeding had no effect on SFA-induced parenchymal apo B. The findings suggest that in a heightened state of cerebrovascular inflammation, the provision of unsaturated fatty acids may be detrimental, possibly as a consequence of a greater susceptibility for oxidation.

Figures

Figure 1

Three-D immunofluorescent staining of cerebral extravasation of apo B. Parenchymal leakage of apo B lipoproteins (red) is observed surrounding the cerebral microvessels. Nuclei are shown in blue. The 3D images are from mice maintained on saturated-fat diet for 5 months (SFA 5 m) and SFA fed mice randomised to LF (+LF 2 m) and DHA (+DHA 2 m) diet for further 2 months. Scale: 1 unit = 42.7 μm.

Figure 2

Three-dimensional (3D) quantitative analysis of apo B leakage in C57BL/6J mouse brain. Pixel intensity of apo B lipoproteins surrounding the cerebrovasculature was quantitated in 3D images from mice maintained on saturated-fat diet for 5 months (SFA 5 m) and SFA-fed mice randomised to LF (+LF 2 m) and DHA (+DHA 2 m) diet for further 2 months. The extent of apo B pixel intensity was measured in the cortex (CTX), brain stem (BS), and hippocampal formation (HPF) and expressed as per unit volume. The bars represent mean intensity and standard error of mean, where P < 0.05 considered statistically significant (* Kruskal Wallis t-test). The C57BL/6J mice randomised to DHA diet (+DHA) had elevated apo B intensities in all regions of the brain.

Figure 3

Effect of dietary fatty acids on plasma S100β concentration in C57BL/6J mice. The brain abundant protein S100β was measured in plasma as a surrogate marker of BBB leakage. High plasma S100β concentration in SFA-fed mice correlate with significant BBB dysfunction. In comparison to SFA 5 m group, plasma S100β was significantly increased in mice switched to the DHA diet (+DHA 2 m). The bars represent mean plasma concentration (pg/mL) and standard error of mean, where P < 0.05 considered statistically significant (* one-way ANOVA).