Identification of CB1-AMPK bridge genes linking metabolic and reproductive dysfunction in polycystic metabolic ovary syndrome

Vishnuvardhan Marella

Mentor: Dr. Qian Zhu, National Center for Advancing Translational Sciences, National Institute of Health..

Date/Time: August 25th, 2026 at 3:45 PM.

Abstract: Polycystic metabolic ovary syndrome (PMOS, previously known as PCOS) is characterized by insulin resistance, chronic low-grade inflammation, adipose dysfunction, and impaired ovarian steroidogenesis. Cannabinoid receptor 1 (CB1) signaling and AMP-activated protein kinase (AMPK) signaling regulate insulin sensitivity, lipid metabolism, inflammation, and steroidogenesis in PMOS. Genes that connect these two signaling pathways may represent molecular convergence points and promising therapeutic targets because of their potential to simultaneously modulate both pathways.

In this study, we identified tissue-specific bridge genes for PMOS by integrating differential expression (DE) of public adipose and granulosa cell/ovarian transcriptomic datasets with CB1 and AMPK pathway gene sets. Protein–protein interaction (PPI) networks were constructed from the resulting tissue-specific gene set, and hub genes were prioritized based on their connectivity to both signaling pathways. The top candidate bridge genes included APOE, SREBF1, CCL2, TNF, and IL10. We then evaluated these candidate bridge genes by collecting literature evidence supporting their associations with both signaling pathways using the NCATS Biomedical Data Translator.