Astrocytes are mainly responsible for the polyunsaturated fatty acid enrichment in blood–brain barrier endothelial cells in vitro

Bernoud, Nathalie; Fénart, Laurence; Bénistant, Christine; Pageaux, Jean‐François; Dehouck, Marie‐Pierre; Molière, Patrick; Lagarde, Michel; Cecchelli, Roméo; Lecerf, Jean

doi:10.1016/s0022-2275(20)32169-6

Cited by 67 publications

(8 citation statements)

References 33 publications

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“…DHA crossing from AceDoPC was significantly higher than from PC, the latter being less efficient than non-esterified DHA [ 53 ]. These results are in agreement with a preferential crossing of the reconstituted BBB model by DHA-LysoPC compared to non-esterified DHA [ 55 ]. The molecular modeling of AceDoPC and DHA-LysoPC showed a very similar 3D structure [ 53 ], differing only by the acetyl moiety at the sn -1 position, and AceDoPC could be recognized by Mfsd2a as well, explaining similar preferential BBB crossing.…”

Section: Transport Of Dha Esterified In Phospholipids To the Brainsupporting

confidence: 86%

Esterification of Docosahexaenoic Acid Enhances Its Transport to the Brain and Its Potential Therapeutic Use in Brain Diseases

Van

Lagarde

2022

Nutrients

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Docosahexaenoic acid-containing lysophosphatidylcholine (DHA-LysoPC) is presented as the main transporter of DHA from blood plasma to the brain. This is related to the major facilitator superfamily domain-containing protein 2A (Mfsd2a) symporter expression in the blood–brain barrier that recognizes the various lyso-phospholipids that have choline in their polar head. In order to stabilize the DHA moiety at the sn-2 position of LysoPC, the sn-1 position was esterified by the shortest acetyl chain, creating the structural phospholipid 1-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC). This small structure modification allows the maintaining of the preferential brain uptake of DHA over non-esterified DHA. Additional properties were found for AceDoPC, such as antioxidant properties, especially due to the aspirin-like acetyl moiety, as well as the capacity to generate acetylcholine in response to the phospholipase D cleavage of the polar head. Esterification of DHA within DHA-LysoPC or AceDoPC could elicit more potent neuroprotective effects against neurological diseases.

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Section: Transport Of Dha Esterified In Phospholipids To the Brainsupporting

confidence: 86%

Esterification of Docosahexaenoic Acid Enhances Its Transport to the Brain and Its Potential Therapeutic Use in Brain Diseases

Van

Lagarde

2022

Nutrients

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“…Astrocytes generally detect peripheral signals because of their physical proximity to blood vessels and play an important role in transporting/storing nutrients in the CNS. Mainly peripherally administered fatty acids accumulate in the astrocytes in the hypothalamus, and these lipid-laden cells display higher expression of GFAP and inflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6) and CCL2 or MCP-1 [267][268][269]. The lipid-laden astrocytes released CCL2, which causes microglia migration and activation, augmenting hypothalamic inflammatory responses [267].…”

Section: B Astrocytesmentioning

confidence: 99%

Hypothalamic inflammation in metabolic disorders and aging

Bhusal

Rahman

Suk

2021

Cell. Mol. Life Sci.

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The hypothalamus is a critical brain region for the regulation of energy homeostasis. Over the years, studies on energy metabolism primarily focused on the neuronal component of the hypothalamus. Studies have recently uncovered the vital role of glial cells as an additional player in energy balance regulation. However, their inflammatory activation under metabolic stress condition contributes to various metabolic diseases. The recruitment of monocytes and macrophages in the hypothalamus helps sustain such inflammation and worsens the disease state. Neurons were found to actively participate in hypothalamic inflammatory response by transmitting signals to the surrounding non-neuronal cells. This activation of different cell types in the hypothalamus leads to chronic, low-grade inflammation, impairing energy balance and contributing to defective feeding habits, thermogenesis, and insulin and leptin signaling, eventually leading to metabolic disorders (i.e., diabetes, obesity, and hypertension). The hypothalamus is also responsible for the causation of systemic aging under metabolic stress. A better understanding of the multiple factors contributing to hypothalamic inflammation, the role of the different hypothalamic cells, and their crosstalks may help identify new therapeutic targets. In this review, we focus on the role of glial cells in establishing a cause-effect relationship between hypothalamic inflammation and the development of metabolic diseases. We also cover the role of other cell types and discuss the possibilities and challenges of targeting hypothalamic inflammation as a valid therapeutic approach.

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“…FAs can also cross the BBB when they are esterified to a glycerol backbone such as lysophosphatidylcholine (lysoPC), which has been shown to be the most efficient form of passage through the BBB (Brossard et al, 1997;Bernoud et al, 1998;Lacombe et al, 2018). In addition to the abovementioned mechanisms, Edmond ( 2001) proposed a model for the specific transport of PUFAs.…”

Section: Transport Across the Bbb Requiring A Transport Proteinmentioning

confidence: 99%

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

2021

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Many prospective studies have shown that a diet enriched in omega-3 polyunsaturated fatty acids (n-3 PUFAs) can improve cognitive function during normal aging and prevent the development of neurocognitive diseases. However, researchers have not elucidated how n-3 PUFAs are transferred from the blood to the brain or how they relate to cognitive scores. Transport into and out of the central nervous system depends on two main sets of barriers: the blood-brain barrier (BBB) between peripheral blood and brain tissue and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) between the blood and the CSF. In this review, the current knowledge of how lipids cross these barriers to reach the CNS is presented and discussed. Implications of these processes in health and disease, particularly during aging and neurodegenerative diseases, are also addressed. An assessment provided here is that the current knowledge of how lipids cross these barriers in humans is limited, which hence potentially restrains our capacity to intervene in and prevent neurodegenerative diseases.

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Astrocytes are mainly responsible for the polyunsaturated fatty acid enrichment in blood–brain barrier endothelial cells in vitro

Cited by 67 publications

References 33 publications

Esterification of Docosahexaenoic Acid Enhances Its Transport to the Brain and Its Potential Therapeutic Use in Brain Diseases

Esterification of Docosahexaenoic Acid Enhances Its Transport to the Brain and Its Potential Therapeutic Use in Brain Diseases

Hypothalamic inflammation in metabolic disorders and aging

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

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