Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease

Pifferi, Fabien; Beaugerie, Laurent; Plourde, Mélanie

doi:10.3389/fphys.2021.645646

Cited by 75 publications

(44 citation statements)

References 87 publications

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“…In order to cross the BBB, there are essentially three potential pathways: passive diffusion through the endothelial membrane, active transport via transfer into the en-dothelium by transmembrane protein transporters (transcytosis), or receptor-mediated endocytosis [68].…”

Section: Discussionmentioning

confidence: 99%

Use of Active Salmon-Lecithin Nanoliposomes to Increase Polyunsaturated Fatty Acid Bioavailability in Cortical Neurons and Mice

Passeri

Elkhoury

Garavito

et al. 2021

IJMS

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Omega-3 polyunsaturated fatty acids (n-3 PUFAs) play an important role in the development, maintenance, and function of the brain. Dietary supplementation of n-3 PUFAs in neurological diseases has been a subject of particular interest in preventing cognitive deficits, and particularly in age-related neurodegeneration. Developing strategies for the efficient delivery of these lipids to the brain has presented a challenge in recent years. We recently reported the preparation of n-3 PUFA-rich nanoliposomes (NLs) from salmon lecithin, and demonstrated their neurotrophic effects in rat embryo cortical neurons. The objective of this study was to assess the ability of these NLs to deliver PUFAs in cellulo and in vivo (in mice). NLs were prepared using salmon lecithin rich in n-3 PUFAs (29.13%), and characterized with an average size of 107.90 ± 0.35 nm, a polydispersity index of 0.25 ± 0.01, and a negative particle-surface electrical charge (−50.4 ± 0.2 mV). Incubation of rat embryo cortical neurons with NLs led to a significant increase in docosahexaenoic acid (DHA) (51.5%, p < 0.01), as well as palmitic acid, and a small decrease in oleic acid after 72 h (12.2%, p < 0.05). Twenty mice on a standard diet received oral administration of NLs (12 mg/mouse/day; 5 days per week) for 8 weeks. Fatty acid profiles obtained via gas chromatography revealed significant increases in cortical levels of saturated, monounsaturated, and n-3 (docosahexaenoic acid,) and n-6 (docosapentaenoic acid and arachidonic acid) PUFAs. This was not the case for the hippocampus or in the liver. There were no effects on plasma lipid levels, and daily monitoring confirmed NL biocompatibility. These results demonstrate that NLs can be used for delivery of PUFAs to the brain. This study opens new research possibilities in the development of preventive as well as therapeutic strategies for age-related neurodegeneration.

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Section: Discussionmentioning

confidence: 99%

Use of Active Salmon-Lecithin Nanoliposomes to Increase Polyunsaturated Fatty Acid Bioavailability in Cortical Neurons and Mice

Passeri

Elkhoury

Garavito

et al. 2021

IJMS

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“…Although it is widely recognized that cholesterol is unable to pass through the blood-brain barrier owing to the presence of tight junctions [167], interestingly, one study has reported direct transport of free cholesterol across the blood-brain barrier via ABCA1 in mice [168]. It also remains possible that physiological and morphological changes to the blood-brain barrier as a result of age or neurodegenerative disease may compromise its permeability, rendering a greater likelihood of leakage of substances, including cholesterol, into and out of the brain [169]. Indeed, increased leakage of oxysterols out of the brain at the blood-brain barrier has been reported in pericyte-deficient mice [170].…”

Section: Direct Export From Brainmentioning

confidence: 99%

Balancing cholesterol in the brain: from synthesis to disposal

Qian

Chai

Gelissen

et al. 2022

Explor Neuroprot Ther

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The cholesterol is a vital component of cell membranes and myelin sheaths, and a precursor for essential molecules such as steroid hormones. In humans, cholesterol is partially obtained through the diet, while the majority is synthesized in the body, primarily in the liver. However, the limited exchange between the central nervous system and peripheral circulation, due to the presence of the blood-brain barrier, necessitates cholesterol in the brain to be exclusively acquired from local de novo synthesis. This cholesterol is reutilized efficiently, rendering a much slower overall turnover of the compound in the brain as compared with the periphery. Furthermore, brain cholesterol is regulated independently from peripheral cholesterol. Numerous enzymes, proteins, and other factors are involved in cholesterol synthesis and metabolism in the brain. Understanding the unique mechanisms and pathways involved in the maintenance of cholesterol homeostasis in the brain is critical, considering perturbations to these processes are implicated in numerous neurodegenerative diseases. This review focuses on the developing understanding of cholesterol metabolism in the brain, discussing the sites and processes involved in its synthesis and regulation, as well as the mechanisms involved in its distribution throughout, and elimination from, the brain.

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“…Interestingly, microglia appear to be highly susceptible to modulation by dietary lipids and other nutrients that are taken up by the brain ( Butler et al., 2020 ; Nadjar et al., 2017 ; Sobesky et al., 2014 ; Spencer et al, 2017 , 2019 ). Preclinical models have shown that SFAs consumed via HFDs can cross the BBB via transport-protein mediated mechanisms ( Pifferi et al., 2021 ). Once in the brain, SFAs can activate toll-like receptors (TLRs), which are located on the surface membrane of innate immune cells like microglia ( Nadjar et al., 2017 ).…”

Section: Brain-resident and Infiltrating Immune Cellsmentioning

confidence: 99%

The role of Western diets and obesity in peripheral immune cell recruitment and inflammation in the central nervous system

Butler

2021

Brain, Behavior, & Immunity - Health

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As the prevalence of obesity and chronic disease increases, the role of nutrition is taking center stage as a potential root cause of not just metabolic-related illnesses, but also of disorders of the central nervous system (CNS). Consumption of a modern, westernized diet, such as a high fat diet (HFD) that contains excess saturated fatty acids (SFAs), refined carbohydrates, and ultra-processed ingredients has been shown to induce neuroinflammation in multiple brain regions important for energy homeostasis, cognitive function, and mood regulation in rodents, non-human primates, and humans. This review article summarizes the literature showing Western diets, via SFA increases, can increase the reactivity and alter the function of multiple types of immune cells from both the innate and adaptive branches of the immune system, with a specific focus on microglia, macrophages, dendritic cells, and T-cells. These changes in immune and neuroimmune signaling have important implications for neuroinflammation and brain health and will be an important factor in future psychoneuroimmunology research.

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Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease

Cited by 75 publications

References 87 publications

Use of Active Salmon-Lecithin Nanoliposomes to Increase Polyunsaturated Fatty Acid Bioavailability in Cortical Neurons and Mice

Use of Active Salmon-Lecithin Nanoliposomes to Increase Polyunsaturated Fatty Acid Bioavailability in Cortical Neurons and Mice

Balancing cholesterol in the brain: from synthesis to disposal

The role of Western diets and obesity in peripheral immune cell recruitment and inflammation in the central nervous system

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