Search

As one of the most common antipsychotics, olanzapine may cause metabolic‐related adverse effects, but it is still unknown how olanzapine alters lipid metabolism. In this study, we found that olanzapine‐treated mice showed varying degrees of dyslipidemia, which was particularly pronounced in female mice. Based on ultra‐performance liquid chromatography–quadrupole time‐of‐flight–MS (UPLC–Q‐TOF–MS) technology and lipid metabolomics, we mapped the changes in lipid metabolism in olanzapine‐treated mice and then compared the changes in lipid metabolism between male and female mice. There were 98 metabolic differentiators between the olanzapine‐treated and control groups in females and 79 in males. These metabolites were glycerolipids, glycerophospholipids, fatty amides, and sphingolipids, which are involved in glycerolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. These results suggest that olanzapine‐induced changes in the levels of lipid metabolites are closely associated with disturbances in lipid metabolic pathways, which may underlie lipemia. This lipidome profiling study not only visualizes changes in lipid metabolism in liver tissue but also provides a foundation for understanding the regulatory pathways and mechanisms involved in olanzapine‐induced lipid metabolism disorders. Furthermore, this study demonstrates differences in lipid metabolism between males and females, providing a reference for clinical treatment regimen selection. [ABSTRACT FROM AUTHOR]

Few studies have examined the relationship between lipid metabolism and kidney stone formation, particularly the role of key lipid regulatory factors in kidney stone formation. We evaluated the effect of the lipid regulatory factor‐peroxisome proliferator‐activated receptor alpha on the formation of renal stones in mice by injecting them with glyoxylate followed by treatment with either a peroxisome proliferator‐activated receptor alpha agonist fenofibrate or an antagonist GW6471 (GW). Liquid chromatography coupled with trapped ion mobility spectrometry‐quadrupole‐time‐of‐flight mass spectrometry‐based lipidomics was used to determine the lipid profile in the mouse kidneys. Histological and biochemical analyses showed that the mice injected with glyoxylate exhibited crystal precipitation and renal dysfunction. Crystallization decreased significantly in the fenofibrate group, whereas it increased significantly in the GW group. A total of 184 lipids, including fatty acyls, glycerolipids, glycerophospholipids, and sphingolipids differed significantly between the mice in the model and control groups. Peroxisome proliferator‐activated receptor alpha activity negatively correlated with glyoxylate‐induced kidney stone formation in mice, which may be related to improved fatty acid oxidation, maintenance of ceramide/complex sphingolipids cycle balance, and alleviation of disorder in phospholipid metabolism. [ABSTRACT FROM AUTHOR]