Rab14 promotes lipophagy and apoptosis of granulosa cells from POAT removed mice

Peri-ovarian adipose tissue (POAT) plays an important role in the regulation of female reproductive, but its specific cellular mechanism is still unclear. Our study aimed to explore the effect of POAT removal on the development of mouse granulosa cells (GCs). We established a POAT-removed model and showed that POAT removal resulted in a significant decrease in litter size, restricted follicle development, and a concomitant increase in GCs apoptosis rate. At the same time, the LDs content in the ovary and GC was significantly reduced. Proteomic analysis revealed that Rab14 expression was upregulated in GC after POAT removal. Functional experiments further showed that Rab14 overexpression significantly enhanced lipophagy activity, reduced the number and volume of LDs, and inhibited the expression of lipid droplet protein PLIN2. Meanwhile, Rab14 overexpression inhibited the phosphorylation level of AKT and induced the apoptosis of granulosa cells, suggesting that Rab14 may activate the cell death pathway mediated by lipophagy. Taken together, POAT may support ovarian function by maintaining lipid homeostasis within GCs. The role of Rab14 in the regulation of lipophagy may link local adipose-derived signaling with GCs survival and female fertility.