# Pyruvate Regulates the Expression of DLAT to Promote Follicular Growth

## TL;DR

Pyruvate promotes follicular growth in mice by regulating DLAT, which supports granulosa cell proliferation and inhibits cell death.

## Contribution

This study reveals a novel mechanism by which pyruvate regulates DLAT to enhance follicular growth.

## Key findings

- Pyruvate shortens pubertal initiation age and promotes follicular growth in mice.
- DLAT upregulation is associated with large follicles and supports granulosa cell proliferation.
- DLAT inhibits granulosa cell apoptosis by binding to CASP3 and CASP9.

## Abstract

Increasing evidence has suggested that dihydrolipoamide S-acetyltransferase (DLAT), a subunit of the pyruvate dehydrogenase complex, is crucial for pyruvate metabolism and the regulation of cell death. The excessive death of granulosa cells (GCs) hinders the progression of follicular growth. However, the relationship between DLAT and follicular growth is poorly understood. Here, we found that pyruvate significantly shortened the age of pubertal initiation in mice and promoted follicular growth by promoting the proliferation of GCs. In addition, pyruvate up-regulated the expression of DLAT and the high level of DLAT was observed in large follicles, which were associated with follicular growth. Mechanistically, DLAT increased the mRNA and protein levels of proliferation pathways such as PCNA and MCL1 to promote GC proliferation. Additionally, DLAT bound to CASP3 and CASP9 proteins to inhibit the apoptosis of GCs. Taken together, these results reveal a mechanism that pyruvate regulated DLAT to promote follicular growth, and DLAT represents a promising target that supports new strategies for improving the growth of follicles.