上睑下垂
炎症体
PCSK9
内分泌学
吡咯喹啉醌
内科学
脂质代谢
低密度脂蛋白受体
化学
生物
炎症
胆固醇
生物化学
医学
脂蛋白
酶
辅因子
作者
Jin‐Yuan Wang,Shun Zhang,Linlin Hu,Yan Wang,Ke Liu,Jianghua Le,Yongpeng Tan,Tianlong Li,Haoxuan Xue,Yanhong Wei,Ou Zhong,Zihe Li,Dan Zi,Xiaoguang Lei,Renhe Deng,Yi‐Bo Luo,Masong Tang,Mark Su,Yu Cao,Qingyou Liu,Zhi‐Han Tang,Xiaocan Lei
标识
DOI:10.1038/s41419-023-06162-8
摘要
Abstract Abnormal lipid metabolism and chronic low-grade inflammation are the main traits of obesity. Especially, the molecular mechanism of concomitant deficiency in steroidogenesis-associated enzymes related to testosterone (T) synthesis of obesity dominated a decline in male fertility is still poorly understood. Here, we found that in vivo, supplementation of pyrroloquinoline quinone (PQQ) efficaciously ameliorated the abnormal lipid metabolism and testicular spermatogenic function from high-fat-diet (HFD)-induced obese mice. Moreover, the transcriptome analysis of the liver and testicular showed that PQQ supplementation not only inhibited the high expression of proprotein convertase subtilisin/Kexin type 9 (PCSK9) but also weakened the NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis, which both played a negative role in T synthesis of Leydig Cells (LCs). Eventually, the function and the pyroptosis of LCs cultured with palmitic acid in vitro were simultaneously benefited by suppressing the expression of NLRP3 or PCSK9 respectively, as well the parallel effects of PQQ were affirmed. Collectively, our data revealed that PQQ supplementation is a feasible approach to protect T synthesis from PCSK9-NLRP3 crosstalk-induced LCs’ pyroptosis in obese men.
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