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Obesity increases blood-brain barrier permeability and aggravates the mouse model of multiple sclerosis. | LitMetric

Obesity increases blood-brain barrier permeability and aggravates the mouse model of multiple sclerosis.

Mult Scler Relat Disord

Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, State University of Campinas, SP, Brazil; Experimental Medicine Research Cluster, University of Campinas, Campinas, Brazil; Obesity and Comorbidities Research Center, University of Campinas, Campinas, Brazil. Electronic address:

Published: April 2023

AI Article Synopsis

  • - Obesity-induced insulin resistance (OIR) is linked to higher rates of neurodegenerative disorders like multiple sclerosis, partly by increasing blood-brain barrier (BBB) permeability in brain regions related to appetite control.
  • - The study found that obese mice on a high-fat diet (HFD) were more vulnerable to experimental autoimmune encephalomyelitis (EAE), exhibiting worsened symptoms and significant spinal cord damage compared to control mice.
  • - Analysis revealed that the severity of EAE in obese mice was associated with higher levels of pro-inflammatory immune cells and BBB disruption, suggesting that OIR drives CNS inflammation and worsens autoimmune responses.

Article Abstract

Obesity-induced insulin resistance (OIR) has been associated with an increased prevalence of neurodegenerative disorders such as multiple sclerosis. Obesity results in increased blood-brain barrier (BBB) permeability, specifically in the hypothalamic regions associated with the control of caloric intake. In obesity, the chronic state of low-grade inflammation has been implicated in several chronic autoimmune inflammatory disorders. However, the mechanisms that connect the inflammatory profile of obesity with the severity of experimental autoimmune encephalomyelitis (EAE) are poorly defined. In this study, we show that obese mice are more susceptible to EAE, presenting a worse clinical score with more severe pathological changes in the spinal cord when compared with control mice. Analysis of immune infiltrates at the peak of the disease shows that high-fat diet (HFD)- and control (chow)-fed groups do not present any difference in innate or adaptive immune cell compartments, indicating the increased severity occurs prior to disease onset. In the setting of worsening EAE in HFD-fed mice, we observed spinal cord lesions in myelinated regions and (blood brain barrier) BBB disruption. We also found higher levels of pro-inflammatory monocytes, macrophages, and IFN-γCD4 T cells in the HFD-fed group compared to chow-fed animals. Altogether, our results indicate that OIR promotes BBB disruption, allowing the infiltration of monocytes/macrophages and activation of resident microglia, ultimately promoting CNS inflammation and exacerbation of EAE.

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Source
http://dx.doi.org/10.1016/j.msard.2023.104605DOI Listing

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