NZO/HlLtJ as a novel model for the studies on the role of metabolic syndrome in acute radiation toxicity

<b>Purpose:</b> Growing rates of metabolic syndrome and associated obesity warrant the development of appropriate animal models for better understanding of how those conditions may affect sensitivity to IR exposure. <b>Materials and methods:</b> We subjected male NZO/HlLtJ mice, a strain prone to spontaneous obesity and diabetes, to 0, 5.5, 6.37, 7.4 or 8.5 Gy (¹³⁷Cs) of total body irradiation (TBI). Mice were monitored for 30 days, after which proximal jejunum and colon tissues were collected for further histological and molecular analysis. <b>Results:</b> Obese NZO/HlLtJ male mice are characterized by their lower sensitivity to IR at doses of 6.37 Gy and under, compared to other strains. Further escalation of the dose, however, results in a steep survival curve, reaching LD_100/30 values at a dose of 8.5 Gy. Alterations in the expression of various tight junction-related proteins coupled with activation of inflammatory responses and cell death were the main contributors to the gastrointestinal syndrome. <b>Conclusions:</b> We demonstrate that metabolic syndrome with exhibited hyperglycemia but without alterations to the microvasculature is not a pre-requisite of the increased sensitivity to TBI at high doses. Our studies indicate the potential of NZO/HlLtJ mice for the studies on the role of metabolic syndrome in acute radiation toxicity.