Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
Pyrroloquinoline Quinone Inhibits PCSK9-NLRP3 Mediated Pyroptosis of Leydig Cells in Obese Mice
51 Pages Posted: 10 Jan 2023
More...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.
Funding Information: The research in authors’ lab has been supported by University of South China, Clinical Anatomy and Reproductive Medicine Application Institute. This work was also supported by the National Natural Science Fund of China (No. 853 82101720), The Natural Science Foundation of Guangxi in China (No. 2022JJA140008), Hunan Province Graduate innovation research projects (No. 223YXC021), Hunan Province Innovation and Entrepreneurship Training Program for College Students (No. S202210555248).
Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Ethics Approval Statement: All experimental procedures were approved by the Animal Ethics Committee of the University of South China (permit number: USC2020031602).
Keywords: Obesity, Testosterone, Leydig Cells, Pyroptosis, PCSK9, NLRP3, Lipid metabolism
Suggested Citation: Suggested Citation