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

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.

Dapagliflozin Ameliorates Ovulation Disorders via Attenuating Activated Microglia-Mediated Hypothalamic Inflammation in HFD-Fed Mice

“…HFD, rich in long-chain saturated fatty acids, permeates the hypothalamus across the BBB and directly activates microglia, which secrete proinflammatory molecules that inhibit GnRH neuron regeneration by acting on its receptors and reducing GnRH secretion by down-regulating kisspeptin signaling [28]. Previous evidences have shown that HFD-induced ovulation disorder is independent of the progression of obesity [29][30][31].…”

Sodium–glucose cotransporter 2 inhibitor ameliorates high fat diet‐induced hypothalamic–pituitary–ovarian axis disorders

“…HFDs enriched with long chain saturated fatty acids (LCSFAs) are known to directly impact the CNS (D'Alonzo et al., 2020 ; Milanski et al., 2009 ; Valdearcos et al., 2014 ). Excessive intake of dietary LCSFAs increases brain–blood barrier (BBB) permeability and induces BBB dysfunction (D'Alonzo et al., 2020 ). With an anatomical proximity to the BBB, the hypothalamus is the front‐line brain region that would be initially affected by any detrimental factors that are leaking through a dysfunctional BBB (Thaler et al., 2012 ).…”

“…3) High-fat diet induces pathological hypothalamic microglia activation. HFDs enriched with long chain saturated fatty acids (LCSFAs) are known to directly impact the CNS (D' Alonzo et al, 2020;Milanski et al, 2009;Valdearcos et al, 2014). Excessive intake of dietary LCSFAs increases brain-blood barrier (BBB) permeability and induces BBB dysfunction (D' Alonzo et al, 2020).…”