Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: a , b Bars (mean ± SD) show serum levels of ( a ) FABP7 and ( b ) FABP4 in RRMS, and age-matched healthy controls (HC1) and in SPMS and age-matched healthy controls (HC2). One-way ANOVA was performed following correction with Šidák multiple comparison test, and P -values are shown above the comparisons ( n = 32 of each group). c A negative correlation of FABP7 with BPF ( n = 34). d , e A positive correlation of FABP7 with T1LV and T2LV ( n = 34). f A positive correlation of serum FABP7 with EDSS score ( n = 98). Two-sided simple linear regression analysis was performed for correlation and shown as a regression line (shaded area represents error of the regression line), data is adjusted for age and sex, and p -values were adjusted using Holm’s correction for ( c – f ). RRMS Relapsing remitting MS, SPMS Secondary progressive MS, BPF Brain Parenchymal Fraction, T1LV whole brain T1 hypointense white matter lesion volume, T2LV whole brain T2 hyperintense white matter lesion volume.

Article Snippet: In this study, we explored the presence of FABP4 and FABP7 in the serum of MS patients where FABP4 and FABP7 were significantly correlated with progressive MS, increased disability and brain atrophy in MS patients and thus FABPs may be incorporated into biomarker panels and algorithms correlating with the clinical stage of MS and potentially subsequent disease course.

Techniques: Comparison

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: Monocytes were treated in vitro with FABP7 or FABP4 for 48 h. Flow cytometry was performed, and data is represented as ( a ) bars (mean ± SD, n = 12) indicating percentage of cell population gated from CD14 + cells from HCs and ( b ) zebra plot showing expression of IL-1β based on FMO. One-way ANOVA was performed following correction with Dunnett’s multiple comparison test for ( a ). c Bars (mean ± SD, n = 9) showing cell populations gated from CD14 + cells in HCs and SPMS. Two-way ANOVA was performed following correction with Šidák multiple comparison test. d zebra plot showing expression of IL-1β. P -values are shown above the comparisons. FMO Fluorescent minus one.

Article Snippet: In this study, we explored the presence of FABP4 and FABP7 in the serum of MS patients where FABP4 and FABP7 were significantly correlated with progressive MS, increased disability and brain atrophy in MS patients and thus FABPs may be incorporated into biomarker panels and algorithms correlating with the clinical stage of MS and potentially subsequent disease course.

Techniques: In Vitro, Flow Cytometry, Expressing, Comparison

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: Monocytes were treated with FABP7 and FABP4 for 48 h, and a seahorse assay was performed. a – e Graphs (mean ± SD) indicate ( a ) OCR and ( b ) ECAR in monocytes treated with FABP7, bar diagram represents ( c ) basal respiration, ( d ) ATP-linked respiration/ATP production and ( e ) basal ECAR ( n = 8 for control and FABP7 and n = 5 for LPS, biological replicates). f , g Graphs (mean ± SD) indicate OCR and ECAR in monocytes treated with FABP4 ( n = 8 for control and FABP4 and n = 5 for LPS, biological replicates). h Monocytes were treated with FABP7 in the presence or absence of 2DG for 48 h, and flow cytometry was performed, data is represented as bars (mean ± SD, n = 24) indicating the percentage of cell population gated from CD14 + cells, and ( i ) zebra plot showing expression of IL-1β. j Effect of FABP7 on ROS production in monocytes of HC. ROS assay was performed in Monocytes treated with FABP7 for 6 h using flow cytometry, and bars represent MFI of ROS positive cells (mean ± SD, n = 5), a representative histogram is also shown for ROS. k Mitochondrial superoxide was determined using flow cytometry after treating the HC monocytes with FABP7 for 48 h, the bar (mean ± SD) represents MFI of MitoSox positive cells ( n = 6), and a representative histogram is also shown for MitoSox. One-way ANOVA was performed following correction with Dunnett’s multiple comparison test for ( c – e , j , and k ), and correction with Šidák multiple comparison test for ( h ). P -values are shown above the comparisons. OCR Oxygen consumption rate, ECAR Extracellular acidification rate, ROS reactive oxygen species.

Article Snippet: In this study, we explored the presence of FABP4 and FABP7 in the serum of MS patients where FABP4 and FABP7 were significantly correlated with progressive MS, increased disability and brain atrophy in MS patients and thus FABPs may be incorporated into biomarker panels and algorithms correlating with the clinical stage of MS and potentially subsequent disease course.

Techniques: Control, Flow Cytometry, Expressing, ROS Assay, Comparison

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: a Volcano plot showing the distribution of overall transcriptomics in monocytes after FABP7 treatment. DESeq2 with a two-sided Wald test was performed for comparison. Data was adjusted for sex. b Heat map showing top 50 DEGs. c Dot plot of gene set enrichment analysis of GO biological pathways using ClusterProfiler. The pathways related to inflammation and chemotaxis were highlighted in the red box. d Pathway analysis of all significant DEGs using Human Cyc 2016 in Enrichr indicates gene enrichment for glucose metabolism. The tests conducted were two-sided, and p -values were adjusted using Benjamini-Hochberg to correct for multiple hypothesis testing for ( c , d ). DEGs Differentially expressed genes.

Article Snippet: In this study, we explored the presence of FABP4 and FABP7 in the serum of MS patients where FABP4 and FABP7 were significantly correlated with progressive MS, increased disability and brain atrophy in MS patients and thus FABPs may be incorporated into biomarker panels and algorithms correlating with the clinical stage of MS and potentially subsequent disease course.

Techniques: Comparison, Chemotaxis Assay

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: a–e SPMS monocytes were treated with FABP7 for 48 h, and a seahorse assay was performed. Graphs (mean ± SD) indicate ( a ) OCR and ( b ) ECAR, bar diagram represents ( c ) basal respiration, ( d ) ATP-linked respiration and ( e ) basal ECAR (mean ± SD, n = 11, biological replicates). f SPMS monocytes were treated with FABP7 in the presence or absence of 2DG for 48 h and flow cytometry was performed, data is represented as bars (mean ± SD, n = 11) indicating the percentage of cell population gated from CD14 + cells. ( g ) Structure and predicted interaction of FABP7 with TLR4-MD2 complex. h , i Isolated monocytes from HC ( n = 12) were incubated with anit-TLR4 antibody following FABP7 treatment for 48 h, and IL-1β was analyzed by flow cytometry and represented as bars (mean ± SD) and zebra plot. A paired two-sided t test was performed for ( c – e ), and one-way ANOVA was performed following correction with Šidák multiple comparison test for ( f and h ). P -values are shown above the comparisons. OCR Oxygen consumption rate, ECAR extracellular acidification rate.

Article Snippet: In this study, we explored the presence of FABP4 and FABP7 in the serum of MS patients where FABP4 and FABP7 were significantly correlated with progressive MS, increased disability and brain atrophy in MS patients and thus FABPs may be incorporated into biomarker panels and algorithms correlating with the clinical stage of MS and potentially subsequent disease course.

Techniques: Flow Cytometry, Isolation, Incubation, Comparison

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: a FABP7 levels were analyzed in CSF of SPMS and non-MS controls using ELISA ( n = 10 for non-MS control, and n = 14 for SPMS). b Brain tissue showing lesion in MS and immunofluorescence images captured at 200X magnification (a small area was further enlarged) showing FABP7 expression (green), GFAP positive astrocytes (bright purple) and nucleus (DAPI: blue) in HC and MS participants. c FABP7 mean fluorescence intensities from five different random areas were quantified and represented as bar (mean ± SD, n = 5), unpaired t-test was performed for ( a and c ). d–j Brain tissue section showing Single cell transcriptome datasets of 20 postmortem brain tissue compartments from 5 MS patients and 3 healthy controls were examined for FABP7 expression and corresponding immune cell gene expression signatures. d UMAP dimensionality reduction plot of 10,767 astrocytes. e FABP7 gene expression in astrocytes from healthy and disease white matter tissue compartments. Indicated p -values of differential gene expression are from the two-sided Wilcoxon Rank Sum test, and p -values were adjusted for multiple testing using Bonferroni correction. f UMAP plot of 5148 immune cells from the same tissue compartments as ( d and e ). g Immune cell marker analysis and cell subset classifications. h Percent change in the relative proportion of immune cell subsets in MS tissue compartments versus healthy control tissue. The percentage of CD14/CD16 double-positive cells is indicated by the color strip on the left. i Statistical associations between astrocyte FABP7 expression and proportions of immune cell subsets from 18 brain tissue microenvironments. Depicted values are Spearman’s rho statistic. j Scatter plots and statistical associations (mean ± SEM) of homeostatic (left) and inflamed (right) microglia with astrocyte FABP7 expression by tissue microenvironments in paired samples was performed using two-sided Spearman’s rho test with no adjustment for multiple correction.

Article Snippet: In this study, we explored the presence of FABP4 and FABP7 in the serum of MS patients where FABP4 and FABP7 were significantly correlated with progressive MS, increased disability and brain atrophy in MS patients and thus FABPs may be incorporated into biomarker panels and algorithms correlating with the clinical stage of MS and potentially subsequent disease course.

Techniques: Enzyme-linked Immunosorbent Assay, Control, Immunofluorescence, Expressing, Fluorescence, Gene Expression, Marker, Stripping Membranes

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: (1) Inflammation and BBB damage cause infiltration of monocytes and other immune in the brain during MS. (2) Activated or dying astrocytes release FABP7 which creates an inflammatory environment for the infiltrating monocytes. (3) The release of FABP7 increases glycolysis in monocytes and triggers TLR4-signaling, leading to increased expression of M1 macrophage associated markers. (4) These M1 macrophages increase the inflammation burden by producing interleukins such as IL-1β and promote demyelination in neurons leading to loss of brain volume. (5) The released FABP7 may cross the disrupted BBB and serve as a biomarker for brain atrophy in MS patients. (Created in BioRender. Patel, R. (2025) https://BioRender.com/i41h044 ).

Article Snippet: In this study, we explored the presence of FABP4 and FABP7 in the serum of MS patients where FABP4 and FABP7 were significantly correlated with progressive MS, increased disability and brain atrophy in MS patients and thus FABPs may be incorporated into biomarker panels and algorithms correlating with the clinical stage of MS and potentially subsequent disease course.

Techniques: Expressing, Biomarker Discovery

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: a , b Bars (mean ± SD) show serum levels of ( a ) FABP7 and ( b ) FABP4 in RRMS, and age-matched healthy controls (HC1) and in SPMS and age-matched healthy controls (HC2). One-way ANOVA was performed following correction with Šidák multiple comparison test, and P -values are shown above the comparisons ( n = 32 of each group). c A negative correlation of FABP7 with BPF ( n = 34). d , e A positive correlation of FABP7 with T1LV and T2LV ( n = 34). f A positive correlation of serum FABP7 with EDSS score ( n = 98). Two-sided simple linear regression analysis was performed for correlation and shown as a regression line (shaded area represents error of the regression line), data is adjusted for age and sex, and p -values were adjusted using Holm’s correction for ( c – f ). RRMS Relapsing remitting MS, SPMS Secondary progressive MS, BPF Brain Parenchymal Fraction, T1LV whole brain T1 hypointense white matter lesion volume, T2LV whole brain T2 hyperintense white matter lesion volume.

Article Snippet: When considered alongside our in vitro results, the correlative postmortem transcriptomics data support a model that astrocyte FABP7 expression perpetuates inflammatory immune activity in chronic MS lesions, potentially contributing to brain atrophy over time in progressive MS patients.

Techniques: Comparison

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: Monocytes were treated in vitro with FABP7 or FABP4 for 48 h. Flow cytometry was performed, and data is represented as ( a ) bars (mean ± SD, n = 12) indicating percentage of cell population gated from CD14 + cells from HCs and ( b ) zebra plot showing expression of IL-1β based on FMO. One-way ANOVA was performed following correction with Dunnett’s multiple comparison test for ( a ). c Bars (mean ± SD, n = 9) showing cell populations gated from CD14 + cells in HCs and SPMS. Two-way ANOVA was performed following correction with Šidák multiple comparison test. d zebra plot showing expression of IL-1β. P -values are shown above the comparisons. FMO Fluorescent minus one.

Article Snippet: When considered alongside our in vitro results, the correlative postmortem transcriptomics data support a model that astrocyte FABP7 expression perpetuates inflammatory immune activity in chronic MS lesions, potentially contributing to brain atrophy over time in progressive MS patients.

Techniques: In Vitro, Flow Cytometry, Expressing, Comparison

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: Monocytes were treated with FABP7 and FABP4 for 48 h, and a seahorse assay was performed. a – e Graphs (mean ± SD) indicate ( a ) OCR and ( b ) ECAR in monocytes treated with FABP7, bar diagram represents ( c ) basal respiration, ( d ) ATP-linked respiration/ATP production and ( e ) basal ECAR ( n = 8 for control and FABP7 and n = 5 for LPS, biological replicates). f , g Graphs (mean ± SD) indicate OCR and ECAR in monocytes treated with FABP4 ( n = 8 for control and FABP4 and n = 5 for LPS, biological replicates). h Monocytes were treated with FABP7 in the presence or absence of 2DG for 48 h, and flow cytometry was performed, data is represented as bars (mean ± SD, n = 24) indicating the percentage of cell population gated from CD14 + cells, and ( i ) zebra plot showing expression of IL-1β. j Effect of FABP7 on ROS production in monocytes of HC. ROS assay was performed in Monocytes treated with FABP7 for 6 h using flow cytometry, and bars represent MFI of ROS positive cells (mean ± SD, n = 5), a representative histogram is also shown for ROS. k Mitochondrial superoxide was determined using flow cytometry after treating the HC monocytes with FABP7 for 48 h, the bar (mean ± SD) represents MFI of MitoSox positive cells ( n = 6), and a representative histogram is also shown for MitoSox. One-way ANOVA was performed following correction with Dunnett’s multiple comparison test for ( c – e , j , and k ), and correction with Šidák multiple comparison test for ( h ). P -values are shown above the comparisons. OCR Oxygen consumption rate, ECAR Extracellular acidification rate, ROS reactive oxygen species.

Article Snippet: When considered alongside our in vitro results, the correlative postmortem transcriptomics data support a model that astrocyte FABP7 expression perpetuates inflammatory immune activity in chronic MS lesions, potentially contributing to brain atrophy over time in progressive MS patients.

Techniques: Control, Flow Cytometry, Expressing, ROS Assay, Comparison

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: a Volcano plot showing the distribution of overall transcriptomics in monocytes after FABP7 treatment. DESeq2 with a two-sided Wald test was performed for comparison. Data was adjusted for sex. b Heat map showing top 50 DEGs. c Dot plot of gene set enrichment analysis of GO biological pathways using ClusterProfiler. The pathways related to inflammation and chemotaxis were highlighted in the red box. d Pathway analysis of all significant DEGs using Human Cyc 2016 in Enrichr indicates gene enrichment for glucose metabolism. The tests conducted were two-sided, and p -values were adjusted using Benjamini-Hochberg to correct for multiple hypothesis testing for ( c , d ). DEGs Differentially expressed genes.

Article Snippet: When considered alongside our in vitro results, the correlative postmortem transcriptomics data support a model that astrocyte FABP7 expression perpetuates inflammatory immune activity in chronic MS lesions, potentially contributing to brain atrophy over time in progressive MS patients.

Techniques: Comparison, Chemotaxis Assay

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: a–e SPMS monocytes were treated with FABP7 for 48 h, and a seahorse assay was performed. Graphs (mean ± SD) indicate ( a ) OCR and ( b ) ECAR, bar diagram represents ( c ) basal respiration, ( d ) ATP-linked respiration and ( e ) basal ECAR (mean ± SD, n = 11, biological replicates). f SPMS monocytes were treated with FABP7 in the presence or absence of 2DG for 48 h and flow cytometry was performed, data is represented as bars (mean ± SD, n = 11) indicating the percentage of cell population gated from CD14 + cells. ( g ) Structure and predicted interaction of FABP7 with TLR4-MD2 complex. h , i Isolated monocytes from HC ( n = 12) were incubated with anit-TLR4 antibody following FABP7 treatment for 48 h, and IL-1β was analyzed by flow cytometry and represented as bars (mean ± SD) and zebra plot. A paired two-sided t test was performed for ( c – e ), and one-way ANOVA was performed following correction with Šidák multiple comparison test for ( f and h ). P -values are shown above the comparisons. OCR Oxygen consumption rate, ECAR extracellular acidification rate.

Article Snippet: When considered alongside our in vitro results, the correlative postmortem transcriptomics data support a model that astrocyte FABP7 expression perpetuates inflammatory immune activity in chronic MS lesions, potentially contributing to brain atrophy over time in progressive MS patients.

Techniques: Flow Cytometry, Isolation, Incubation, Comparison

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: a FABP7 levels were analyzed in CSF of SPMS and non-MS controls using ELISA ( n = 10 for non-MS control, and n = 14 for SPMS). b Brain tissue showing lesion in MS and immunofluorescence images captured at 200X magnification (a small area was further enlarged) showing FABP7 expression (green), GFAP positive astrocytes (bright purple) and nucleus (DAPI: blue) in HC and MS participants. c FABP7 mean fluorescence intensities from five different random areas were quantified and represented as bar (mean ± SD, n = 5), unpaired t-test was performed for ( a and c ). d–j Brain tissue section showing Single cell transcriptome datasets of 20 postmortem brain tissue compartments from 5 MS patients and 3 healthy controls were examined for FABP7 expression and corresponding immune cell gene expression signatures. d UMAP dimensionality reduction plot of 10,767 astrocytes. e FABP7 gene expression in astrocytes from healthy and disease white matter tissue compartments. Indicated p -values of differential gene expression are from the two-sided Wilcoxon Rank Sum test, and p -values were adjusted for multiple testing using Bonferroni correction. f UMAP plot of 5148 immune cells from the same tissue compartments as ( d and e ). g Immune cell marker analysis and cell subset classifications. h Percent change in the relative proportion of immune cell subsets in MS tissue compartments versus healthy control tissue. The percentage of CD14/CD16 double-positive cells is indicated by the color strip on the left. i Statistical associations between astrocyte FABP7 expression and proportions of immune cell subsets from 18 brain tissue microenvironments. Depicted values are Spearman’s rho statistic. j Scatter plots and statistical associations (mean ± SEM) of homeostatic (left) and inflamed (right) microglia with astrocyte FABP7 expression by tissue microenvironments in paired samples was performed using two-sided Spearman’s rho test with no adjustment for multiple correction.

Article Snippet: When considered alongside our in vitro results, the correlative postmortem transcriptomics data support a model that astrocyte FABP7 expression perpetuates inflammatory immune activity in chronic MS lesions, potentially contributing to brain atrophy over time in progressive MS patients.

Techniques: Enzyme-linked Immunosorbent Assay, Control, Immunofluorescence, Expressing, Fluorescence, Gene Expression, Marker, Stripping Membranes

Journal: Nature Communications

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

doi: 10.1038/s41467-025-60747-9

Figure Lengend Snippet: (1) Inflammation and BBB damage cause infiltration of monocytes and other immune in the brain during MS. (2) Activated or dying astrocytes release FABP7 which creates an inflammatory environment for the infiltrating monocytes. (3) The release of FABP7 increases glycolysis in monocytes and triggers TLR4-signaling, leading to increased expression of M1 macrophage associated markers. (4) These M1 macrophages increase the inflammation burden by producing interleukins such as IL-1β and promote demyelination in neurons leading to loss of brain volume. (5) The released FABP7 may cross the disrupted BBB and serve as a biomarker for brain atrophy in MS patients. (Created in BioRender. Patel, R. (2025) https://BioRender.com/i41h044 ).

Article Snippet: When considered alongside our in vitro results, the correlative postmortem transcriptomics data support a model that astrocyte FABP7 expression perpetuates inflammatory immune activity in chronic MS lesions, potentially contributing to brain atrophy over time in progressive MS patients.

Techniques: Expressing, Biomarker Discovery