Tauroursodeoxycholic acid ameliorates palmitic acid induced endoplasmic reticulum stress and impaired autophagy via IRE1- XBP1-FoxO1 pathway in KGN cells.

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder among women of childbearing age. Patients with PCOS often have elevated levels of palmitic acid (PA) in their blood and follicular fluid. Granulosa cells (GCs) play crucial roles in follicular development and oocyte maturation. Whether the development of PCOS is related to an increase in PA, which affects GC function, and the underlying mechanisms remain unclear. Tauroursodeoxycholic acid is important for the treatment of metabolic diseases; however, whether it protects GCs remains unknown. In this study, KGN human GCs were treated with PA for 24 h to determine the effects of PA on GCs and elucidate the underlying mechanisms. PA treatment activated the inositol-requiring enzyme 1 pathway and promoted the expression of X-box binding protein 1, which interacted with forkhead box protein O1 and promoted its ubiquitination and degradation. This decreased the levels of autophagy-related gene 7 and inhibited cellular autophagy, leading to impaired mitochondrial function. However, tauroursodeoxycholic acid application reduced inositol-requiring enzyme 1 phosphorylation and promoted autophagy in KGN cells via the X-box binding protein 1-forkhead box protein O1 pathway, thereby restoring the mitochondrial function. Overall, these findings enhance our understanding of the molecular basis of GC impairment in patients with PCOS and provide potential therapeutic targets for their treatment.