Adult-Onset CNS Sulfatide Deficiency Causes Sex-Dependent Metabolic Disruption in Aging.
Int J Mol Sci
; 24(13)2023 Jun 22.
Article
em En
| MEDLINE
| ID: mdl-37445661
ABSTRACT
The interconnection between obesity and central nervous system (CNS) neurological dysfunction has been widely appreciated. Accumulating evidence demonstrates that obesity is a risk factor for CNS neuroinflammation and cognitive impairment. However, the extent to which CNS disruption influences peripheral metabolism remains to be elucidated. We previously reported that myelin-enriched sulfatide loss leads to CNS neuroinflammation and cognitive decline. In this study, we further investigated the impact of CNS sulfatide deficiency on peripheral metabolism while considering sex- and age-specific effects. We found that female sulfatide-deficient mice gained significantly more body weight, exhibited higher basal glucose levels, and were glucose-intolerant during glucose-tolerance test (GTT) compared to age-matched controls under a normal diet, whereas male sulfatide-deficient mice only displayed glucose intolerance at a much older age compared to female sulfatide-deficient mice. Mechanistically, we found that increased body weight was associated with increased food intake and elevated neuroinflammation, especially in the hypothalamus, in a sex-specific manner. Our results suggest that CNS sulfatide deficiency leads to sex-specific alterations in energy homeostasis via dysregulated hypothalamic control of food intake.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sulfoglicoesfingolipídeos
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Doenças Neuroinflamatórias
Tipo de estudo:
Etiology_studies
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Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article