PP269 - SEX-STRATIFIED HEPATIC EXPRESSION OF FATTY ACID OXIDATION AND KETONE METABOLISM PROTEINS IN DIO-STZ AND CHOW-FED MICE

PP269

SEX-STRATIFIED HEPATIC EXPRESSION OF FATTY ACID OXIDATION AND KETONE METABOLISM PROTEINS IN DIO-STZ AND CHOW-FED MICE

V. V. Witt^1,2, S. Gödecke², A. Heinen², S. B. Berkemeyer^1,*, A. Gödecke²

¹NutritionLab, Hochschule Osnabrück, Osnabrueck, ²Institut für Herz- und Kreislaufphysiologie, Medizinische Fakultät, Heinrich-Heine-Universität Düsseldorf , Düsseldorf, Germany

Rationale: The diet-induced obesity–streptozotocin (DIO-STZ) mouse is an established model of type 2 diabetes mellitus (T2DM). We investigated whether hepatic proteins involved in fatty acid oxidation and ketone metabolism - CPT2, HMGCS2, BDH1, PDK4, and OXCT1 - differ between male and female DIO-STZ mice and sex-matched chow-fed controls.

Methods: 6 male and 6 female C57BL/6J mice were rendered diabetic by high-fat, high-sucrose feeding plus low-dose streptozotocin according to a published protocol (Heinen et al.), 6 male and 6 female chow-fed mice were controls. Hepatic protein abundance was measured by Western blot quantified by densitometry relative to housekeeping proteins. Statistical analyses were performed for males and females using unpaired two-tailed Student’s t-tests with p<0.05 considered statistically significant.

Results: In males, DIO-STZ induced significantly higher hepatic HMGCS2 (p<0.001) and PDK4 (p<0.01) protein expression, but reduced OXCT1 (p<0.01), compared with male chow-fed controls; BDH1 and CPT2 were also increased, although not significantly. In female DIO-STZ mice significantly higher hepatic HMGCS2, PDK4, CPT2, and BDH1 expression than female chow-fed controls (all p<0.05), whereas OXCT1 did not differ significantly between groups.

Conclusion: In the DIO-STZ model, males exhibit an isolated shift toward ketone production with reduced utilization, while females show a coordinated upregulation of fatty acid oxidation and ketone metabolism. These sex-dependent metabolic adaptations suggest that T2DM-induced hepatic remodeling requires distinct, sex-specific investigations.

References: Heinen, Andre, et al. "Combined high-fat, high sucrose diet and streptozotocin treatment induces cardiometabolic heart failure with preserved ejection fraction in mice." American Journal of Physiology-Heart and Circulatory Physiology (2026). doi: 10.1152/ajpheart.00843.2025.

Disclosure of Interest: None declared