How the Oviduct Lipidomic Profile Changes over Time after the Start of an Obesogenic Diet in an Outbred Mouse Model

SIMPLE SUMMARY: This study investigated the lipidomic changes in the oviduct at different time points (from 3 days to 16 weeks) during feeding an obesogenic diet, in an outbred mouse model. We used MALDI mass spectrometry imaging focusing on changes in the oviductal epithelium (OE). The obesogenic diet resulted in an overall higher average peak intensity of all detected lipids, and we could identify differentially regulated lipids (DRLs) already after 3 days. The number of DRLs progressively increased and became more persistent after long-term obesogenic diet feeding. Functional annotation revealed that the alterations were mainly in phospholipids, sphingomyelins and lysophospholipids. ABSTRACT: We investigated whether a high-fat/high-sugar (HF/HS) diet alters the lipidomic profile of the oviductal epithelium (OE) and studied the patterns of these changes over time. Female outbred Swiss mice were fed either a control (10% fat) or HF/HS (60% fat, 20% fructose) diet. Mice (n = 3 per treatment per time point) were sacrificed and oviducts were collected at 3 days and 1, 4, 8, 12 and 16 weeks on the diet. Lipids in the OE were imaged using matrix-assisted laser desorption ionisation mass spectrometry imaging. Discriminative m/z values and differentially regulated lipids were determined in the HF/HS versus control OEs at each time point. Feeding the obesogenic diet resulted in acute changes in the lipid profile in the OE already after 3 days, and thus even before the development of an obese phenotype. The changes in the lipid profile of the OE progressively increased and became more persistent after long-term HF/HS diet feeding. Functional annotation revealed a differential abundance of phospholipids, sphingomyelins and lysophospholipids in particular. These alterations appear to be not only caused by the direct accumulation of the excess circulating dietary fat but also a reduction in the de novo synthesis of several lipid classes, due to oxidative stress and endoplasmic reticulum dysfunction. The described diet-induced lipidomic changes suggest alterations in the OE functions and the oviductal microenvironment which may impact crucial reproductive events that take place in the oviduct, such as fertilization and early embryo development.