Effect of lycium barbarum polysaccharide on ameliorating high-fat diet-damaged spermatogenesis via PCSK9 and TLR4 signaling pathways in obese mice.

BACKGROUND

Obesity-induced chronic inflammation is a significant contributor to male infertility, primarily by disrupting Sertoli cell function and impairing spermatogenesis. Lycium barbarum polysaccharides (LBP), the principal bioactive constituents of wolfberries, exhibit a range of pharmacological effects, including anti-inflammatory, antioxidant, and anti-apoptotic activities.

OBJECTIVE

Herein, we are committed to verifying whether LBP conferred inflammatory and apoptosis inhibition against obese spermatogenic dysfunction.

METHODS

Purified LBP was assessed for its effects on male fertility preservation in vivo. RNA-seq analysis was also employed to confirm the latent mechanism.

RESULTS

In vivo, We found that LBP significantly reversed lipid accumulation and regulated the secretion of inflammatory factors (MyD88, NF-κB, NLRP3), proliferation and apoptosis factors (Bax, Bcl2), and blood-testis barrier (BTB) markers (ZO-1, Ocln, CX43). This protective effect promoted Sertoli cell proliferation and improved semen quality in obese mice. The results showed that LBP treatment reduced cellular apoptosis. This was accompanied by increased expression of BTB-related proteins and restored anti-inflammatory activity. These findings suggest that PCSK9 and TLR4 accelerates Sertoli cell dysfunction under high-lipid conditions, while LBP intervention strongly reverses this dysfunction.

CONCLUSION

Collectively, these robust findings demonstrate that LBP alleviates high-fat diet-induced inflammatory responses and apoptosis by blocking the PCSK9 and TLR4 axis, improving BTB integrity and Sertoli cell dysfunction, and ultimately mitigating diet-induced male infertility.