ArticleInternational journal of molecular sciences2026
Sex Differences in Dietary-Induced Liver Steatosis and Insulin Receptor-Related Signaling in Aged Mice Lacking Serotonin Transporter.
Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Sex differences remain largely underexplored in metabolic disorders, particularly in the context of genetic predisposition to type 2 diabetes, the impact of aging, and environmental factors such as exposure to high-caloric diets. Previous studies using serotonin transporter (SERT)-knockout (SERT-KO) mice, which recapitulate metabolic conditions related to the lowered function of this transporter in humans, revealed an aggravated negative response of these mutants to housing on a high-fat/sugar 'Western diet' (WD). However, the role of sex in SERT-KO mice has not yet been studied. Available human and animal data suggest the differential regulation of insulin receptor-mediated signaling in males and females, which can be altered with aging. This study aimed to compare fat accumulation, blood biochemical changes, glucose tolerance, and insulin receptor (IR)-related signaling in the liver and various brain structures of 12-month-old male and female SERT-KO mice fed WD for 21 days. Relative to the dietary-unchallenged group and their wild-type (WT) littermates, WD-fed mutants of both sexes displayed markedly increased fat accumulation and impaired glucose and insulin tolerance. Body mass increase was more prominent in females than in males. The two sexes revealed a similar suppression of the gene expression of isoforms A and B of IR but distinct expression of IR-related factors. IR-related genes such as
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