Chronic Consumption of Bovine Dairy Milk Attenuates Dietary Saturated Fatty Acid-Induced Blood-Brain Barrier Dysfunction.

Zachary D'Alonzo,Virginie Lam,Michael Nesbit,John C. L. Mamo,Ryu Takechi,Liam Graneri

doi:10.3389/fnut.2020.00058

Abstract

Ingestion of Western-diets enriched in long chain saturated fatty acids (LCSFA) are associated with increased risk of blood-brain barrier (BBB) dysfunction and neurovascular inflammation. Potential mechanisms include vascular insult as a consequence of metabolic aberrations, or changes in capillary permeability resulting in brain parenchymal extravasation of pro-inflammatory molecules. Bovine dairy milk (BDM) is potentially a significant source of dietary LCSFA, however, BDM contains an array of bioactive molecules purported to have vascular anti-inflammatory properties. This study investigated the effects of full cream (4% total fat) and delipidated (skim) BDM on BBB integrity and neuroinflammation in wild-type mice. Mice consuming substantial amounts of full cream or skim BDM with LCSFA-enriched chow were dyslipidemic compared to control mice provided with standard chow and water. However, there was no evidence of BBB dysfunction or neuroinflammation indicated by parenchymal abundance of immunoglobulin G and microglial recruitment, respectively. Positive control mice maintained on an LCSFA-enriched diet derived from cocoa-butter and water, had marked BBB dysfunction, however, co-provision of both full cream and skim milk solutions effectively attenuated LCSFA-induced BBB dysfunction. In mice provided with low-fat chow and full cream BDM drinking solutions, there were substantial favorable changes in the concentration of plasma anti-inflammatory cytokines. This study suggests that consumption of BDM may confer potent vascular benefits through the neuroprotective properties exuded by the milk-fat globule membrane moiety of BDM.

Highlights

Risk factors for vascular dysfunction such as dyslipidaemia and obesity are associated with early onset and progression of neurodegenerative disorders such as Alzheimer’s disease and vascular dementia [1]
This study investigated the putative effects of chronic ingestion of full cream or skim Bovine dairy milk (BDM) on neurovascular integrity and neuroinflammation in genetically unmanipulated wild-type mice
Provision of the long chain saturated fatty acids (LCSFA) diet alone had no significant effect on water intake compared to mice on a low-fat diet, but a significant increase in the intake of both full cream and skim solutions was seen in the LCSFA + FC and LCSFA + Skim groups

Summary

Introduction

Risk factors for vascular dysfunction such as dyslipidaemia and obesity are associated with early onset and progression of neurodegenerative disorders such as Alzheimer’s disease and vascular dementia [1]. Chronic ingestion of Western-styled diets enriched in long chain saturated fatty acids (LCSFA) exacerbate metabolic parameters that results in a chronic state of inflammation which can lead to vascular dysfunction [2,3,4]. Exaggerated intake of dietary LCSFA has been shown to increase blood-brain barrier (BBB) permeability by reducing expression of tight-junction proteins in cerebral endothelium [5]. The latter is thought to occur as a consequence of exaggerated endothelial exposure to circulating pro-inflammatory cytokines [6, 7]. In genetically un-manipulated mice maintained on a modestly LCSFA-enriched diet, plasma-derived proteins and macromolecules were indicated within brain parenchyme, triggering microglial and astrocyte activation, exacerbating neurovascular inflammation [8]

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Conclusion