PMID- 37660522 OWN - NLM STAT- MEDLINE DCOM- 20231201 LR - 20231217 IS - 2300-732X (Electronic) IS - 1642-431X (Linking) VI - 23 IP - 4 DP - 2023 Dec TI - LC-MS-based untargeted metabolomics reveals the mechanism underlying prostate damage in a type 2 diabetes mouse model. PG - 100811 LID - S1642-431X(23)00083-9 [pii] LID - 10.1016/j.repbio.2023.100811 [doi] AB - Type 2 diabetes mellitus (T2DM) can cause prostate damage and affect male reproductive function, but the underlying mechanisms are not completely understood. In this study, we used liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics to identify endogenous metabolites in the prostate of a T2DM mouse model. The selected endogenous metabolites were then subjected to bioinformatics analysis and metabolic pathway studies to understand their role in the development of T2DM-induced prostate damage. We used male homozygous BTBR ob/ob mice (n = 12) and BTBR WT mice (n = 11) in this study. We monitored changes in blood glucose, body weight, prostate weight, and prostate index, as well as performed hematoxylin and eosin (H&E) staining and observed that the prostate of the BTBR ob/ob was damaged. We then used ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) for metabolomics analysis. The stability of the model was validated using principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). Using variable importance in projection (VIP) > 1, false discovery rate (FDR) < 0.05, and coefficient of variation (CV) < 30 as criteria, a total of 149 differential metabolites (62 upregulated and 87 downregulated) were identified between the prostates of the two groups of mice. Topological pathway analysis showed that these differential metabolites were mainly involved in sphingolipid (SP) and glycerophospholipid (GP) metabolism. In conclusion, our study not only emphasizes the damage caused by T2DM to the prostate but also provides new insights into the potential mechanisms of T2DM-induced male reproductive dysfunction. CI - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Qi, Rong AU - Qi R AD - Clinical Medical College, North China University of Science and Technology, Tangshan 063210, China. FAU - Kang, Shao-San AU - Kang SS AD - Clinical Medical College, North China University of Science and Technology, Tangshan 063210, China. FAU - Pei, Yongchao AU - Pei Y AD - Clinical Medical College, North China University of Science and Technology, Tangshan 063210, China. FAU - Liu, Mingming AU - Liu M AD - School of Public Health, North China University of Science and Technology, Tangshan 063210, China. FAU - Zhou, Yufan AU - Zhou Y AD - School of Public Health, North China University of Science and Technology, Tangshan 063210, China. FAU - Guan, Bo AU - Guan B AD - School of Public Health, North China University of Science and Technology, Tangshan 063210, China. FAU - Zhang, Xinduo AU - Zhang X AD - School of Public Health, North China University of Science and Technology, Tangshan 063210, China. FAU - Li, Zhiguo AU - Li Z AD - School of Public Health, North China University of Science and Technology, Tangshan 063210, China. Electronic address: lizhiguo@ncst.edu.cn. FAU - Cao, Fenghong AU - Cao F AD - Clinical Medical College, North China University of Science and Technology, Tangshan 063210, China. Electronic address: caofenghong@163.com. LA - eng PT - Journal Article DEP - 20230901 PL - Poland TA - Reprod Biol JT - Reproductive biology JID - 101160559 RN - 0 (Biomarkers) SB - IM MH - Male MH - Mice MH - Animals MH - Chromatography, Liquid/methods MH - *Diabetes Mellitus, Type 2 MH - Prostate/metabolism MH - Tandem Mass Spectrometry MH - Metabolomics/methods MH - Disease Models, Animal MH - Biomarkers/metabolism OTO - NOTNLM OT - Glycerophospholipid OT - Metabolomics OT - Prostate OT - Sphingolipid OT - Type 2 diabetes mellitus COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/09/04 00:41 MHDA- 2023/12/01 06:45 CRDT- 2023/09/03 18:05 PHST- 2023/05/30 00:00 [received] PHST- 2023/08/18 00:00 [revised] PHST- 2023/08/24 00:00 [accepted] PHST- 2023/12/01 06:45 [medline] PHST- 2023/09/04 00:41 [pubmed] PHST- 2023/09/03 18:05 [entrez] AID - S1642-431X(23)00083-9 [pii] AID - 10.1016/j.repbio.2023.100811 [doi] PST - ppublish SO - Reprod Biol. 2023 Dec;23(4):100811. doi: 10.1016/j.repbio.2023.100811. Epub 2023 Sep 1.