Introduction and Objective: Mice housed at ambient temperature (22°C) experience increased heat production to maintain core temperature, leading to higher total energy expenditure than at 30°C. In this study, we examined the metabolic effects of Survodutide, a dual glucagon/GLP-1 receptor agonist, at ambient housing temperature (30°C) to assess the impact of thermoneutrality in the polygenic type 2 diabetic NZO/HILtJ mouse model.Methods: Adult male NZO/HILtJ mice (6 weeks) were maintained on a high-fat diet (D12492) for two weeks before being randomized (n=8/group) to receive either Vehicle (Saline) or Survodutide (30 nmol/kg, s.c, QD, 2 weeks) under thermoneutral (30°C) conditions.Results: Survodutide treatment resulted in a ~15% decrease in body weight over two weeks and significantly reduced food intake by ~33% (2.5g vs. 3.6g/day), indicating its strong impact on energy balance regulation.Vehicle-treated mice had a total fat mass of 24.68 g, whereas the Survodutide-treated group exhibited a reduced fat mass of 19.12 g (p<0.001).Additionally, while vehicle-treated mice gained 2.7% lean mass from baseline, Survodutide treatment led to a decrease of -2.4%. Blood glucose levels were significantly lower in Survodutide-treated mice (145 ± 18 mg/dL) compared to vehicle-treated controls (200 ± 21 mg/dL, p<0.04). Indirect calorimetry analysis revealed that although Survodutide reduced calorie intake, it also decreased energy expenditure.Conclusion: Overall, Survodutide treatment under thermoneutral conditions reduced body weight, fat mass, food intake, and blood glucose levels in NZO/HILtJ mice, while also lowering energy expenditure, emphasizing the role of environmental temperature in metabolic drug effects.
J. Swagel: None. S. Olkkola: None. K.A. Eschete: None. A. Dunn: None. N. Bethur: None. H. Kaur: None. T. Stodola: None. B. Hoffmann: None. K. O’Connell: None. V. Yin: None. A. .: None.
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