Effect of High Fructose Diet (HFrD) on Insulin Signaling in Ovarian Tissues of Hepatic PKCε Heterozygous Female Mice

Introduction: High-fat diets have been associated with metabolic complications and obesity. However, increasing evidence shows high fructose consumption significantly contributes to obesity and metabolic complications including insulin resistance. Insulin resistance is strongly associated with the development of metabolic syndrome, affecting thousands globally. PKCε phosphorylates and inhibits the insulin receptor. We hypothesize that the hepatic deletion of PKCε in female mice on HFrD will enhance insulin signaling. Methods: Heterozygous LivPKCε (PKCεfl/Δ) female mice were fed either a control diet (Cntrl, Research Diets Inc, RDI D12450J) or a high fructose diet (HFrD, RDI D02022704) for a month. At the end of one month, a subset of these mice was injected 0.5 U/kg of insulin before being sacrificed and ovarian tissues harvested. Protein expression in the ovaries was assessed by western blot. Protein concentrations in the tissue samples were equalized with BCA assays. The action of insulin was measured molecularly by examining p-AKT Serine 473 (positive regulator, Santa Cruz sc-514032). Breeding for homozygous LivPKCε (Δ/Δ) mice was ongoing. Results: Data revealed that LivPKCε (fl/Δ) HFrD-fed female mice had about a 2-fold increase in p-AKT expression when stimulated with insulin compared to the insulin control with the basal control group displaying considerably lower p-AKT levels. This indicates notable diet-induced shifts in insulin signaling. P is significant “(p<0.05; n=2-4)". Conclusion: This finding indicates that PKCε deletion may modulate insulin sensitivity in ovarian tissues, potentially protecting against insulin resistance upon exposure to HFrD. This may indicate that improved insulin signaling may not only be limited to the liver but also seen systemically. It alters metabolites in the blood that likely alters the ovaries. Further studies in female homozygous LivPKCε (Δ/Δ) mice are needed to provide additional insights into the specific roles of PKCε in ovarian tissues. Funding information We would like to thank the National Science Foundation for award NSF1931045 and the National Institutes of Health for award 1R01DK126892-01A1. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.