FRI288 Single-Cell Transcriptomics Identifies Pituitary Gland Cell Type Population Changes In Diet Induced Obesity

Abstract

Abstract Disclosure: R.E. Ruggiero-Ruff: None. B. Le: None. N. Lainez: None. D. Coss: None. Obesity is a worldwide growing public health concern, with a current prevalence of 43% in the United States and projected future increase. Obesity is associated with type 2 diabetes, cardiovascular disease, stroke, and endocrine abnormalities. The pituitary gland is the master gland that responds to metabolic perturbations and regulates homeostasis via hormone secretion. Thyrotrophic, gonadotropic, somatotropic, lactotropic and corticotropic dysfunctions may occur as a consequence of obesity and perpetuate pathophysiologic conditions since pituitary hormones regulate metabolic function in return. Previous work from our lab determined that mice fed high fat diet have reduced levels of gonadotropin hormones, indicating that diet-induced obesity may play a role in pituitary hormone production. We postulate that diet-induced obesity alters the pituitary transcriptome and/or select population changes. To determine the effect of diet-induced obesity on pituitary gland population plasticity, we performed single-cell RNA-sequencing (scRNA-seq) of pituitary glands from control and high-fat diet-fed mice and characterized population changes and gene expression changes in each population. While gonadotrope population changes levels of gene expression that results in the lower gonadotropin levels, somatotrope and lactotrope populations, on the other hand, change at the population level with alterations in the cell numbers that result in altered levels of growth hormone and prolactin in the circulation. In summary, we defined diet-induced changes in pituitary hormone production and population shifts that may play a role in altered hormone production in obese patients and consequently dysregulation of homeostasis. Presentation: Friday, June 16, 2023