Elevated Linoleic Acid Intake Becomes a Risk Factor for Polycystic Ovary Syndrome by Affecting Ovarian Granulosa Cells

Abstract

Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in females of reproductive age; this condition is particularly concerning due to its potential to cause infertility. Linoleic acid (LA) is an essential and widely consumed n−6 polyunsaturated fatty acid. In the past decades, LA intake has sharply surged, as recommended by dietary guidelines and advances in the food industry. An increasing number of people are questioning the health benefits of LA. In patients with PCOS, dietary management is crucial for improving symptoms to obtain good outcomes with assisted reproductive technology (ART). Diets rich in n−6 fatty acid has become “arch-criminal” of “silent inflammation.” PCOS is also associated with low-grade chronic inflammation. Therefore, identification of the relationship between dietary LA and PCOS is urgently required. In this study, we first conducted experiments to observe the effects of different LA concentrations on PCOS-related phenotypes in mice. The results showed that medium and high concentrations of LA led to PCOS-like changes in mice, presenting with disordered estrous cycles, polycystic ovaries, and hyperandrogenism. LA is independent of PCOS-related weight gain and insulin resistance. LA caused systemic inflammation, reduced antioxidant capacity, and increased ovary apoptosis in mice. To explore how LA acts in vivo, we used the ovarian granulosa cell line KGN to detect alterations in the levels of granulosa cells (GCs). In addition to having no impact on endocrine function, LA can decrease the antioxidant capacity, reduce mitochondrial function, increase the apoptotic rate, and induce inflammation in GCs. To obtain more information, the pretreated GCs were subjected to transcriptome sequencing. The abundant RNA-Seq results make future directions for understanding the mechanism of LA action on GCs in PCOS more explicit. In summary, elevated LA intake is a risk factor for PCOS that affects ovarian GCs. Further studies should focus on establishing a strict intake range for the prevention and treatment of PCOS.