Journal article

Publication year: 2020

Journal: JCI Insight

Volume number: 5

Issue number: 21

eISSN: 2379-3708

Open access status: Gold

DOI Link: https://doi.org/10.1172/jci.insight.134882

Publisher: American Society for Clinical Investigation

Abstract: 
Metabolic syndrome (MetS), which is associated with chronic inflammation, predisposes males to hypogonadism and subfertility. The underlying mechanism of these pathologies remains poorly understood. Homozygous leptin-resistant obese db/db mice are characterized by small testes, low testicular testosterone, and a reduced number of Leydig cells. Here we report that IL-1 beta, CCL2 (also known as MCP-1), and corticosterone concentrations were increased in the testes of db/db mice relative to those in WT controls. Cultured marine and human Leydig cells responded to cytokine stress with increased CCL2 release and apoptotic signals. Chemical inhibition of CCL2 rescued Leydig cell function in vitro and in db/db mice. Consistently, we found that CCL2-deficient mice fed with a high-energy diet were protected from testicular dysfunction compared with similarly fed WT mice. Finally, a cohort of infertile men with a history of MetS showed that reduction of CCL2 plasma levels could be achieved by weight loss and was clearly associated with recovery from hypogonadism. Taken together, we conclude that CCL2-mediated chronic inflammation is, to a large extent, responsible for the subfertility in MetS by causing damage to Leydig cells.

Harvard Citation style: Jiang, Q., Maresch, C., Petry, S., Paradowska-Dogan, A., Bhushan, S., Chang, Y., et al. (2020) Elevated CCL2 causes Leydig cell malfunction in metabolic syndrome, JCI Insight, 5(21), Article e134882. https://doi.org/10.1172/jci.insight.134882

APA Citation style: Jiang, Q., Maresch, C., Petry, S., Paradowska-Dogan, A., Bhushan, S., Chang, Y., Wrenzycki, C., Schuppe, H., Houska, P., Hartmann, M., Wudy, S., Shi, L., & Linn, T. (2020). Elevated CCL2 causes Leydig cell malfunction in metabolic syndrome. JCI Insight. 5(21), Article e134882. https://doi.org/10.1172/jci.insight.134882