Work

The estrous cycle moderates the food and body weight suppressive effects of glucagon‐like peptide‐1 receptor agonism

Year: 2025

Type: article

Abstract: AIMS: Emerging data suggest more young women than men are prescribed weight loss pharmacotherapies targeting the glucagon-like peptide-1 receptor (GLP-1R). However, preclinical literature has largely used male animals to characterize the neural mechanisms underlying the weight loss abilities of GLP-1R agonists (GLP-1RAs), highlighting a need for female-specific investigations. Recently, we described data pointing to the female estrous cycle as a possible moderator of GLP-1RA's effects in rats. Expression of brainstem Glp1r and the GLP-1 precursor gene, Gcg, increased during two estrous phases, proestrus and estrus (P/E), compared to males and compared to other phases, metestrus and diestrus (M/D). On this basis, we hypothesized that the weight-reducing effects of GLP-1RAs may be potentiated during P/E. MATERIALS AND METHODS: In separate experiments, we determined whether timing administration of acute liraglutide or chronic semaglutide to either P/E or M/D would moderate food intake and weight loss in female rats maintained on a high fat diet. We also used qPCR to explore estrous cycle-dependent variation in Glp1r within widely distributed nuclei relevant to energy balance control. RESULTS: GLP-1RA administration during P/E, compared to M/D, enhanced the intake-suppressive effects of liraglutide and semaglutide. Moreover, semaglutide administered only during P/E led to greater body weight loss compared to M/D-administered semaglutide. We also observed greater Glp1r expression in P/E compared to M/D in multiple nuclei. CONCLUSIONS: GLP-1RAs administered in P/E lead to significantly greater body weight loss via reduction in food intake. Collectively, these data may have translational implications for the timing of GLP-1RA administration across the menstrual cycle.

Source: Diabetes Obesity and Metabolism

DOI: 10.1111/dom.70177

Authors: Sarah V. Applebey, Allison G. Xiao, Benjamin C. Reiner, Matthew R. Hayes

Institution: University of Pennsylvania

Language: English

Topic: Regulation of Appetite and Obesity

Subfield: Endocrine and Autonomic Systems

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,380