Neuregulin 4 improves white adipose tissue inflammation in mice with polycystic ovary syndrome.

BACKGROUND

Neuregulin 4 (Nrg4), a secretory peptide predominantly derived from brown adipose tissue (BAT), has been verified to play roles in multiple metabolic disorders. Nevertheless, the role of Nrg4 in the pathogenesis of PCOS remains largely unelucidated.

METHODS

Female C57BL/6 J mice were randomly divided into NC, PCOS, AAV-Luc, and AAV-Nrg4 group. Mice in the AAV-Luc group received AAV-Luc injection, while those in the AAV-Nrg4 group received AAV-Nrg4 injection into the BAT in the scapular region. One week after virus injection, the PCOS model was established. The weight, intraperitoneal glucose tolerance test and serum sex hormone were detected at the eighth week after virus injection. Then, the mice were sacrificed. The expression of Nrg4 in BAT was detected. The histological morphology of the ovaries and and WAT were observed. The expression of steroid synthasesin the ovaries, inflammatory factors and adiponectin in WAT were detected. Further, the expression of macrophage polarization markers in WAT were measured. Finally, the ErbB4/PI3K/AKT signaling pathway related proteins were detected.

RESULTS

In PCOS mice, overexpression of Nrg4 in BAT led to reduction of body weight, improvement of glucose tolerance, restoration of the estrous cycle, and decrease in serum testosterone estrogen and luteinizing hormone levels. This treatment also reduced the levels of pro-inflammatory factors. Additionally, Nrg4 overexpression suppressed the expression of CYP17A1 and StAR in ovarian tissue and enhanced the expression of CYP19A1. Finally, the ErbB4/PI3K/AKT signaling pathway was intensely activated in WAT.

CONCLUSION

Nrg4 can improve WAT inflammation and ovarian steroidogenesis and follicular development in PCOS mice.