A Regionally Inspired West Virginia Obesogenic Diet Induces Fat Accretion and Metabolic Dysfunction While Identifying Sex Disparity

Kelley, E. E.; Giromini, A. P.; Maxwell, B. A.; Spears, A. L.; Lewis, S. E.; Salvatore, S. R.; Fazzari, M.; Balaji, S.; Fagone, P.; Konopa, E. A.; Saporito, D. C.; King, J. A.; Schopfer, F. J.; Khoo, N. K.; McCarthy, P.; Hollander, J. M.; Leonardi, R.

doi:10.64898/2026.02.16.706140

bioRxiv · 10.64898/2026.02.16.706140

A Regionally Inspired West Virginia Obesogenic Diet Induces Fat Accretion and Metabolic Dysfunction While Identifying Sex Disparity

Kelley, E. E.·Giromini, A. P.·Maxwell, B. A.·Spears, A. L.·Lewis, S. E.·Salvatore, S. R.·Fazzari, M.·Balaji, S.·Fagone, P.·Konopa, E. A.·Saporito, D. C.·King, J. A.·Schopfer, F. J.·Khoo, N. K.·McCarthy, P.·Hollander, J. M.·Leonardi, R.

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Abstract

Obesity prevalence continues to rise in the United States, with a disproportionate burden falling to West Virginia. To investigate the metabolic effects of region-specific dietary patterns, we developed the West Virginia Obesogenic Diet (WV-OD), a compositionally defined rodent diet based on nutritional analyses of meals consumed by obese individuals in the state. The WV-OD closely mirrors the macronutrient profile of the average American diet while incorporating regional features such as a greater sodium level and significantly less fiber. We compared the metabolic effects of the WV-OD to a matched control diet (WV-CD) and to a widely used high-fat diet (HFD, 60% of calories derived from fat) in male and female C57BL/6J mice. After 19 weeks, WV-OD-fed males exhibited weight gain and adiposity comparable to HFD-fed counterparts, along with glucose intolerance and hepatic triglyceride accumulation confirming the obesogenic and metabolically disruptive properties of the WV-OD. Unlike HFD-fed mice, WV-OD-fed males also displayed elevated circulating cholesterol and cholesterol esters without corresponding increases in hepatic total cholesterol. When compared to the HFD, the WV-OD did not increase uric acid or xanthine oxidoreductase (XOR) content of liver or circulation; however, both males and females on the WV-OD demonstrated trends towards elevated plasma uric acid. Interestingly, while exhibiting a similar caloric intake on either diet, the WV-OD females did not demonstrate significant fat accretion or metabolic dysfunction compared to females subjected to the 60% HFD. In toto, these findings: 1) establish the WV-OD as a regionally-grounded, yet broadly representative tool for modeling diet-induced obesity and metabolic dysfunction, 2) offer a physiologically relevant alternative to extreme-fat dietary models in preclinical research and 3) highlight sex-based differences in response to diet-induced obesity.

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Kelley, E. E., Giromini, A. P., Maxwell, B. A., Spears, A. L., Lewis, S. E., Salvatore, S. R., Fazzari, M., Balaji, S., Fagone, P., Konopa, E. A., Saporito, D. C., King, J. A., Schopfer, F. J., Khoo, N. K., McCarthy, P., Hollander, J. M., Leonardi, R.. 2026-02-18. A Regionally Inspired West Virginia Obesogenic Diet Induces Fat Accretion and Metabolic Dysfunction While Identifying Sex Disparity. https://doi.org/10.64898/2026.02.16.706140

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