Liver PKCε heterozygous mice (LivPKCε fl/Δ) showed improved high-fat-diet–induced glucose intolerance after one month

Introduction: Chronic consumption of a high-fat diet (HFD) leads to hepatic lipid accumulation and impaired glucose homeostasis, often resulting in glucose intolerance and diet-induced obesity. Hepatic protein kinase Cε (PKCε) has been identified as an important mediator of metabolic dysfunction, but its role in regulating glucose tolerance remains incompletely defined. Although whole-body PKCε deletion has been reported to protect against diet-induced glucose intolerance, findings are inconsistent, and the specific contribution of liver PKCε is unclear. Here, we used liver-specific PKCε–deficient mice to determine how hepatic PKCε deletion influences glucose tolerance under control and high-fat dietary conditions. Hypothesis: Based on conflicting reports that PKCε–/– mice may be protected from diet-induced insulin resistance or glucose intolerance, we hypothesized that hepatic PKCε deletion would improve glucose intolerance in mice exposed to an HFD. Methods: Liver-specific PKCε–deficient mice were generated using the Cre/loxP system to produce heterozygous LivPKCε fl/Δ mice. Male and female mice were assigned to either a control diet (Research Diets D12450J; 20% protein, 70% carbohydrate, 10% fat) or an HFD (Research Diets D12492; 20% protein, 20% carbohydrate, 60% fat) and maintained on their diets for one month. Glucose tolerance tests (2 g/kg, intraperitoneal) were performed after a 6-hour fast at the end of the dietary intervention. Results: After one month of feeding, LivPKCε fl/Δ mice exhibited improved glucose tolerance under HFD conditions, demonstrated by comparable glucose responses between control- and HFD-fed mice (P > 0.05). Conclusion: Although the role of tissue-specific PKCε deletion in metabolic regulation remains debated, our preliminary findings indicate that hepatic PKCε deletion improves HFD-induced glucose intolerance in heterozygous mice. Ongoing studies will evaluate homozygous liver-specific knockouts (LivPKCε Δ/Δ) and wild-type littermates to enable more comprehensive metabolic and molecular analyses. Support or Funding Information: This work was supported by the National Science Foundation (NSF #1931045) and the National Institutes of Health (NIH R01DK126892-01A1). This abstract was presented at the American Physiology Summit 2026 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.