High-resolution untargeted metabolomics reveals altered lysophosphatidylcholine, palmitoleic acid, triglycerides, and isopulegone caffeate associated with ovarian injury in BTBR ob/ob mice

Diabetes mellitus adversely affects female reproductive health, leading to ovarian dysfunction and infertility. In this study, we investigated metabolic alterations in the ovaries of BTBR ob/ob mice, a well-established type 2 diabetes mellitus model, using high-resolution untargeted metabolomics combined with ion mobility spectrometry. Our analysis identified significant changes in key lipid metabolites, including polyunsaturated lysophosphatidylcholine, palmitoleic acid, triglyceride and isopulegone caffeate, which are closely linked to inflammatory and oxidative stress pathways. Notably, the decrease in anti-inflammatory polyunsaturated lysophosphatidylcholines and antioxidant isopulegone caffeate, along with the increase in pro-inflammatory palmitoleic acid and triglycerides, is accompanied by reduced interleukin-6 levels and elevated monocyte chemoattractant protein-1 expression. This indicates that the ovarian microenvironment has been disrupted and shifted toward inflammation. In addition, the increase in 4-hydroxynonenal, a marker of oxidative damage, further confirms that the vicious cycle of inflammation and oxidative stress leads to ovarian injury. These findings reveal the key metabolic disorders underlying diabetes-induced ovarian dysfunction, suggesting that polyunsaturated lysophosphatidylcholine, palmitoleic acid, triglycerides and isopulegone caffeate may be potential metabolic regulators and therapeutic targets in diabetic ovarian injury. However, their exact roles and mechanisms still need to be clarified through further functional studies.