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

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Davanzo, Gustavo Gastao ; Castro, Gisele ; Monteiro, Lauar de Brito ; Castelucci, Bianca Gazieri ; Jaccomo, Vitor Hugo ; Silva, Felipe Correa da ; Marques, Ana Maria ; Francelin, Carolina ; Campos, Bruna Bueno de ; Aguiar, Cristhiane Favero de ; Joazeiro, Paulo Pinto ; Consonni, Silvio Roberto ; Farias, Alessandro dos Santos ; Moraes-Vieira, Pedro M.

• Tipo de documento: Artigo Científico
• Fonte: MULTIPLE SCLEROSIS AND RELATED DISORDERS; v. 72, p. 7-pg., 2023-03-10.

Resumo

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, spe-cifically 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-gamma+CD4+ 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 mono-cytes/macrophages and activation of resident microglia, ultimately promoting CNS inflammation and exacer-bation of EAE. (AU)

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