Impact of Sex on Plasma Biomarkers in ob/ob Mice

TL;DR

This study shows that sex influences plasma biomarkers in a mouse model of metabolic disease, highlighting the importance of considering sex in biomedical research.

Contribution

The study identifies sex-specific differences in plasma proteins in ob/ob mice and links them to patterns observed in human NASH patients.

Findings

27% of quantified plasma proteins showed sex differences in ob/ob mice, with most elevated in females.

Enolase 2 (ENO2) was consistently elevated in female ob/ob mice and showed a similar pattern in female NASH patients.

The findings emphasize the importance of incorporating sex as a biological variable in metabolic disease research.

Abstract

Sex is a critical biological variable that influences disease incidence, progression, and therapeutic responses; therefore, it must be incorporated into biomedical research. Despite this, most mouse studies historically have not compared animals by sex. Recently, growing evidence has indicated that sex-specific analyses are important in obesity and metabolic disorders. The ob/ob mouse is a widely used model for metabolic disease research; however, sex differences in plasma biomarkers have not been fully characterized in this model. In this study, male and female ob/ob mice at 8 weeks of age exhibited comparable body weight, blood glucose levels, and adipose tissue mass. Plasma proteomics analysis using the Olink platform revealed that 27% (23/84) of quantified proteins exhibited sex differences, with 91% (21/23) of these proteins elevated in females. Notably, Enolase 2 (ENO2), also known as neuron-specific enolase (NSE), was consistently elevated in female ob/ob mice and showed a similar sex-associated pattern in female patients with non-alcoholic steatohepatitis (NASH). While the human NASH data provide correlative support rather than direct clinical validation, these observations underscore the importance of considering sex as a biological variable in metabolic disease research. Incorporating sex-specific biomarker profiles may help refine mechanistic interpretation and inform future studies toward personalized therapeutic approaches.

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