Leptin haploinsufficiency exerts sex-dependent partial protection in SOD1G93A mice by reducing inflammatory pathways in the adipose tissue.
Sci Rep
; 14(1): 2671, 2024 02 01.
Article
em En
| MEDLINE
| ID: mdl-38302474
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by significant metabolic disruptions, including weight loss and hypermetabolism in both patients and animal models. Leptin, an adipose-derived hormone, displays altered levels in ALS. Genetically reducing leptin levels (Lepob/+) to maintain body weight improved motor performance and extended survival in female SOD1G93A mice, although the exact molecular mechanisms behind these effects remain elusive. Here, we corroborated the sexual dimorphism in circulating leptin levels in ALS patients and in SOD1G93A mice. We reproduced a previous strategy to generate a genetically deficient leptin SOD1G93A mice (SOD1G93ALepob/+) and studied the transcriptomic profile in the subcutaneous adipose tissue and the spinal cord. We found that leptin deficiency reduced the inflammation pathways activated by the SOD1G93A mutation in the adipose tissue, but not in the spinal cord. These findings emphasize the importance of considering sex-specific approaches in metabolic therapies and highlight the role of leptin in the systemic modulation of ALS by regulating immune responses outside the central nervous system.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esclerose Lateral Amiotrófica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article