Androgen regulates seasonal changes in triglyceride synthesis through the AR-SREBP1-FASN axis in the scented glands of muskrats (Ondatra zibethicus)

Abstract

SREBP1 (sterol regulatory element binding protein 1) plays an important role in maintaining lipid balance in mammals. Previous research showed that androgen significantly regulated the secretion of lipid-rich musky odor substances from the scented glands of muskrats. Our investigation provides insights into the pathways through which androgen induces SREBP1 expression and affects seasonal changes in triglyceride synthesis in muskrat scented glands. During the breeding season, pronounced Oil Red O staining was confirmed in the scented glandular tissues, and transmission electron microscopy displayed a marked increase in lipid droplets. The scented glands exhibited a higher triglyceride content, which coincided with augmented circulating testosterone, dihydrotestosterone, as well as increased scented glandular testosterone and dihydrotestosterone concentrations. Transcriptomic, proteomic and metabolomic analyses of the scented glands revealed associations with fatty acid biosynthesis, while plasma metabolomic data indicated an increase in metabolites serving as precursors during the breeding season for de novo fatty acid synthesis. Expression levels of genes and proteins related to lipid synthesis and lipid droplets, as well as FASN activity, were significantly elevated in the breeding season. Immunolocalization studies demonstrated the presence of these proteins in glandular and epithelial cells in both seasons. Moreover, in vitro treatment of the scented glandular cells with testosterone resulted in elevated expressions of triglyceride synthesis-related genes. These findings suggested that androgen modulates triglyceride synthesis to enhance lipid droplet formation via the AR-SREBP1-FASN Axis in the scented glands of muskrats, thereby shedding light on the hormonal regulation of lipid metabolism in seasonal breeders.