Liraglutide alters hepatic gene expression more significantly in female and OVX prediabetic rats

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 38% of the global population, with nearly 70% of Type 2 Diabetes (T2D) patients also suffering from it. Current treatments often fall short, highlighting the need for comprehensive therapeutic benefits. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like liraglutide are approved for T2D and obesity, offering benefits like weight loss, glycemic control, and reduced cardiovascular risk. Emerging research suggests GLP-1 RA effects can be sex-specific, with women potentially experiencing greater weight loss and varying glucose homeostasis responses. Additionally, menopause influences GLP-1 RA efficacy, underscoring the importance of understanding these sex and reproductive status-dependent differences.

Researchers investigated the effects of Liraglutide on metabolic disorders associated with prediabetes in a rat model. The study compared responses across male, fertile-aged female, and ovariectomized (OVX) female rats. The primary focus was to analyze changes in hepatic gene expression related to lipogenesis, fatty acid and lipid metabolism, and fibrosis. While specific doses, routes, or durations of Liraglutide treatment were not detailed in the abstract, the design aimed to elucidate sex- and reproductive status-dependent differences in metabolic outcomes. Gene expression was assessed for markers such as Scd-1, Srebp1, Pparγ, Pparα, Hmgcr, Srebp2, and Tgfβ to evaluate hepatic lipid metabolism and fibrosis.

Liraglutide treatment induced significant changes in hepatic gene expression profiles in prediabetic rats, with notable sex- and reproductive status-dependent variations. Compared to male rats, both female and ovariectomized (OVX) female rats exhibited more pronounced alterations in genes involved in lipogenesis, fatty acid and lipid metabolism, and fibrosis. Specifically, female and OVX female rats showed more significant changes in the expression of lipogenesis-related genes, including Scd-1, Srebp1, and Pparγ. Furthermore, genes crucial for fatty acid and lipid metabolism, such as Pparα, Hmgcr, and Srebp2, were also more significantly modulated in these female groups. The study also observed greater changes in the fibrosis marker Tgfβ in female and OVX female rats.

Females of fertile age demonstrated improved hepatic lipid metabolism, suggesting a protective or more responsive metabolic profile to liraglutide compared to males or post-menopausal models.