CNS myelination and remyelination depend on fatty acid synthesis by oligodendrocytes

Dimas, Penelope Maria; Montani, Laura; Pereira, Jorge A.; Moreno, Daniel Antunes; Trötzmüller, Martin; Gerber, Joanne; Semenkovich, Clay F.; Köfeler, Harald; Suter, Ueli

doi:10.7554/elife.44702

Cited by 113 publications

(86 citation statements)

References 55 publications

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“…SREBP1, like other SREBPs, is activated by a reduction of intracellular cholesterol, indicating a homeostatic link between fatty acid synthesis and cholesterol synthesis [108,109]. De novo fatty acid synthesis is critical for the correct formation and growth of myelin both in the PNS and in the CNS [33,48,[110][111][112]. Animals ablated for fatty acid synthase (encode by Fasn) in either Schwann cells or oligodendrocytes present a partial block in the onset and efficiency of myelination.…”

Section: Fatty Acid Synthesismentioning

confidence: 99%

“…Recently, fatty acid uptake was proposed to compensate partially for deficiencies in fatty acid synthesis in both the CNS and the PNS [110,111]. Compensation by fatty acid uptake was more evident in myelinating cells in direct proximity to blood vessels or indirectly from an increase in horizontal flux of fatty acids through astrocytes or adipocytes [33,110].…”

Section: Fatty Acid Uptakementioning

confidence: 99%

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Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Poitelon

Kopec

Belin

2020

Cells

244

152

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Myelin is critical for the proper function of the nervous system and one of the most complex cell–cell interactions of the body. Myelination allows for the rapid conduction of action potentials along axonal fibers and provides physical and trophic support to neurons. Myelin contains a high content of lipids, and the formation of the myelin sheath requires high levels of fatty acid and lipid synthesis, together with uptake of extracellular fatty acids. Recent studies have further advanced our understanding of the metabolism and functions of myelin fatty acids and lipids. In this review, we present an overview of the basic biology of myelin lipids and recent insights on the regulation of fatty acid metabolism and functions in myelinating cells. In addition, this review may serve to provide a foundation for future research characterizing the role of fatty acids and lipids in myelin biology and metabolic disorders affecting the central and peripheral nervous system.

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Section: Fatty Acid Synthesismentioning

confidence: 99%

Section: Fatty Acid Uptakementioning

confidence: 99%

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Poitelon

Kopec

Belin

2020

Cells

244

152

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“…The analysis of this mouse model demonstrated that the major source of myelin lipids are astrocytes. [10] However, when lipid synthesis is inactivated in astrocytes, OLs are able to bypass this deficiency by recruiting dietary lipids for myelin membrane synthesis [22].…”

Section: Biosynthesis Of Fatty Acids and Sphingolipidsmentioning

confidence: 99%

“…However, the role of modulators of lipid metabolism in OPC-mediated repair is still not completely elucidated. Of note, recent studies suggest that targeting the lipid pathways in OLs may be a good strategy to promote remyelination [10].Furthermore, in MS, remyelination failure is also strictly correlated to an altered extracellular signaling microenvironment that, among others, affects the organization of OL membranes, which causes defects in myelin at the molecular level [11,12]. Although the ECM is one of the main elements that constitute the central nervous system (CNS) parenchyma, new roles for the ECM components in regeneration and repair responses to CNS injury have only recently been documented.…”

mentioning

confidence: 99%

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Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair

Marangon

Boccazzi

Lecca

et al. 2020

JCM

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Myelin is an essential structure that protects axons, provides metabolic support to neurons and allows fast nerve transmission. Several neurological diseases, such as multiple sclerosis, are characterized by myelin damage, which is responsible of severe functional impairment. Myelin repair requires the timely recruitment of adult oligodendrocyte precursor cells (OPCs) at the lesion sites, their differentiation and maturation into myelinating oligodendrocytes. As a consequence, OPCs undergo profound changes in their morphology, functions, and interactions with other cells and extracellular environment, thus requiring the reorganization of both their lipid metabolism and their membrane composition, which is substantially different compared to other plasma membranes. Despite the growing knowledge in oligodendroglia biology and in the mechanisms involved in OPC-mediated regeneration, the identification of strategies to promote remyelination still remains a challenge. Here, we describe how altered lipid metabolism in oligodendrocytes influences the pathogenesis of demyelination, and we show that several FDA-approved drugs with a previously unknown remyelination potential do act on cholesterol and lipid biosynthetic pathways. Since the interplay between myelin lipids and axons is strictly coordinated by the extracellular matrix (ECM), we also discuss the role of different ECM components, and report the last findings on new ECM-modifiers able to foster endogenous remyelination.Damage to myelin sheath is present in different severe neurological conditions such as multiple sclerosis (MS), brain ischemia, and amyotrophic lateral sclerosis (ALS). Loss of myelin ultimately results in reduction of nerve conduction velocity and in altered transfer of energy metabolites to neurons which contribute to disease [5,6]. Myelin repair, through the activation, recruitment and differentiation of adult oligodendrocyte precursor cells (OPCs), which become new myelin forming OLs [7], is crucial for limiting axon degeneration and progressive disease disability. During the remyelination process, OPCs undergo profound morphological and functional changes and progressively remodel their membrane composition, increasing the biosynthesis of cholesterol and galactosphingolipids, and reducing the relative amount of phospholipids and proteins [4]. An intricate interaction of environmental signals and cell-intrinsic mechanisms triggered by the immune and inflammatory response to injury is known to limit the regenerative potential of OPCs in MS [8,9]. However, the role of modulators of lipid metabolism in OPC-mediated repair is still not completely elucidated. Of note, recent studies suggest that targeting the lipid pathways in OLs may be a good strategy to promote remyelination [10].Furthermore, in MS, remyelination failure is also strictly correlated to an altered extracellular signaling microenvironment that, among others, affects the organization of OL membranes, which causes defects in myelin at the molecular level [11,12]. Although the ECM is ...

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Novel insights into brain lipid metabolism in Alzheimer's disease: Oligodendrocytes and white matter abnormalities

Kawade

Yamanaka

2023

FEBS Open Bio

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Alzheimer's disease (AD) is the most common cause of dementia. A genome‐wide association study has shown that several AD risk genes are involved in lipid metabolism. Additionally, epidemiological studies have indicated that the levels of several lipid species are altered in the AD brain. Therefore, lipid metabolism is likely changed in the AD brain, and these alterations might be associated with an exacerbation of AD pathology. Oligodendrocytes are glial cells that produce the myelin sheath, which is a lipid‐rich insulator. Dysfunctions of the myelin sheath have been linked to white matter abnormalities observed in the AD brain. Here, we review the lipid composition and metabolism in the brain and myelin and the association between lipidic alterations and AD pathology. We also present the abnormalities in oligodendrocyte lineage cells and white matter observed in AD. Additionally, we discuss metabolic disorders, including obesity, as AD risk factors and the effects of obesity and dietary intake of lipids on the brain.

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CNS myelination and remyelination depend on fatty acid synthesis by oligodendrocytes

Cited by 113 publications

References 55 publications

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair

Novel insights into brain lipid metabolism in Alzheimer's disease: Oligodendrocytes and white matter abnormalities

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