FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switch

Multiple sclerosis (MS) involves dysregulation of innate immune cells including monocytes, especially in progressive MS. Fatty acid binding proteins (FABP) are essential for fatty acid transport and metabolism in multiple cell types. FABP7, a brain-FABP, maintains metabolic function in astrocytes an...

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Bibliographic Details
Published in:Nature communications Vol. 16; no. 1; pp. 6049 - 18
Main Authors: Patel, Rohit, King, Devin, LaBarre, Brenna, Lokhande, Hrishikesh, Caefer, Danielle, Varghese, Johnna F., Warner, Keturah, Bouffard, Marc A., Saxena, Shrishti, Zhirova, Alena, Bakshi, Rohit, Chitnis, Tanuja
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.07.2025
Nature Publishing Group
Nature Portfolio
Subjects:
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Adult
Age
Amyotrophic lateral sclerosis
Astrocytes
Astrocytes - metabolism
Biomarkers
Biomarkers - blood
Biomarkers - cerebrospinal fluid
Brain
Brain - metabolism
Brain - pathology
CD16 antigen
CD80 antigen
Cerebrospinal fluid
Chemotaxis
Cytokines
Demography
Disease
Fatty acid-binding protein
Fatty Acid-Binding Protein 7 - blood
Fatty Acid-Binding Protein 7 - genetics
Fatty Acid-Binding Protein 7 - metabolism
Fatty Acid-Binding Proteins - blood
Fatty Acid-Binding Proteins - metabolism
Fatty acids
Female
Gene expression
Genotype & phenotype
Glucose metabolism
Glycolysis
Humanities and Social Sciences
Humans
Immune system
Inflammation
Inflammation - metabolism
Interleukin-1beta - metabolism
Lesions
Lipids
Male
Middle Aged
Monocytes
Monocytes - immunology
Monocytes - metabolism
multidisciplinary
Multiple sclerosis
Multiple Sclerosis - metabolism
Multiple Sclerosis, Chronic Progressive - blood
Multiple Sclerosis, Chronic Progressive - immunology
Multiple Sclerosis, Chronic Progressive - metabolism
Multiple Sclerosis, Chronic Progressive - pathology
Neural stem cells
Neuroimaging
Pathogenesis
Peripheral blood
Phenotype
Phenotypes
Science
Science (multidisciplinary)
Stem cells
Therapeutic targets
Tumor Suppressor Proteins
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Multiple sclerosis (MS) involves dysregulation of innate immune cells including monocytes, especially in progressive MS. Fatty acid binding proteins (FABP) are essential for fatty acid transport and metabolism in multiple cell types. FABP7, a brain-FABP, maintains metabolic function in astrocytes and neural stem cells, but the effect of FABP7 on monocytes is unknown. Here we find elevated levels of FABP7 in the serum and cerebrospinal fluid of patients with secondary progressive MS. Elevated serum FABP7 levels positively correlate with higher disability scores, brain lesion volumes, and lower brain volumes. FABP7 levels are increased in astrocytes from MS postmortem brain lesion. Mechanistically, in vitro treatment of FABP7 induces CD16, CD80 and IL-1β expression in monocytes via increased glycolysis. FABP7-induced gene expression reflects enhanced inflammation, chemotaxis and glucose metabolism in monocytes. In conclusion, we find that FABP7 induces pro-inflammatory profiles in monocytes, correlates with disability and represents a potential biomarker and therapeutic target for progressive MS. While immune dysregulation is acknowledged as causal for multiple sclerosis (MS), how monocytes contribute to MS etiology is still unclear. Here the authors analyze peripheral blood and cerebrospinal fluid samples as well as brain MRI image data from MS patients to implicate FABP7 in alteration of monocyte glycolysis, and as a potential marker for MS progression.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-025-60747-9