Leptin haploinsufficiency exerts sex-dependent partial protection in SOD1^G93A mice by reducing inflammatory pathways in the adipose tissue.

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

SUBMITTER: Fernandez-Beltran LC 

PROVIDER: S-EPMC10834470 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature