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.

Nutraceutical agents with anti-inflammatory properties prevent dietary saturated-fat induced disturbances in blood–brain barrier function in wild-type mice

“…The integrity of the cerebrovascular BBB was assessed by an established method of cerebral plasma protein extravasation that indicates the unspecific blood-to-brain leakage of plasma proteins and macromolecules [9,11,12,17,18,37,38]. Briefly, 3-D quantitative immunomicroscopy was used to assess brain parenchymal abundance of IgG (Mw 155 kDa) and of apoB lipoproteins (molecular weight > 2×10 7 kDa).…”

“…Studies in animal models support the latter. Wild-type mice chronically fed pro-inflammatory diets enriched in saturated fatty acids (SFA) or cholesterol showed hallmark features of BBB dysfunction including cerebral extravasation of large plasma proteins (immunoglobulin G (IgG) and macromolecules (apolipoprotein (apo) B lipoproteins)) concomitant with diminished endothelial tight junction proteins [9,11-13]. …”

“…However, paradoxical observations have been reported in other studies. Provision of omega-3 fatty acids to mice that had been maintained on an SFA enriched diet for twelve weeks, exacerbated measures of BBB dysfunction [11]. A study by Mustata et al also showed increased glycoxidation in tendon, aorta, and plasma by anti-oxidative green tea and vitamins C and E in a diabetic rat model [21].…”

Restoration of dietary-fat induced blood–brain barrier dysfunction by anti-inflammatory lipid-modulating agents

“…Three-dimensional (3-D) images were captured through ApoTome optical sectioning methodology (Carl Zeiss) [35,58]. Each 3-D image consisted of 6–10 two-dimensional images and the distance between Z-stack slices was 1·225 μm optimised by Nyquist.…”

Omega 3, 6, 9 Enhanced Goat Meat (Omega-Chevon) from Flaxseed and Canola Fed Meat Goats

“…Flax contains about 20% alpha linolenic acid, an essential omega-3 fatty acid, a precursor for Eicosapentaenoic Acid (EPA), which is a precursor for eicosanoids, hormone-like compounds involved in the immune response (Cathcart, Lysaght, & Pidgeon, 2011;Hogenkamp et al, 2011;Kapoor & Huang, 2006). The precursor EPA can elongate further to Docosahexanoic Acid (DHA), an omega-3 fatty acid that is essential for cell membrane integrity, as well as brain and eye health (Jicha & Markesbery, 2010;Kiecolt-Glaser, Belury, Andridge, Malarkey, & Glaser, 2011;Lauretani et al, 2007;Pallebage-Gamarallage, Lam, Takechi, Galloway, & Mamo, 2012).…”