Chaudhary Rajesh, Suhan Tahra K, Wu Chao, Alzamrooni Afnan, Madamanchi Nageswara, Abdel-Latif Ahmed
Division of Cardiology, Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, 48105, USA; Ann Arbor VA Healthcare System, 2215 Fuller Rd, Ann Arbor, MI, 48105, USA.
University of Michigan, Ann Arbor, MI, 48105, USA.
Mol Cell Endocrinol. 2025 Mar 1;598:112457. doi: 10.1016/j.mce.2025.112457. Epub 2025 Jan 7.
Preclinical heart failure studies rely heavily on mouse models despite their higher metabolic and heart rates compared to humans. This study examines how mouse strain (C57BL/6J vs. C57BL/6N) and housing temperature (23 °C vs. 30 °C) affect a well-established two-hit HFpEF model using high-fat diet with L-NAME treatment in male C57BL/6 mouse. Metabolic parameters and cardiac function were assessed at baseline, week 5, and week 15. Thermoneutral housing (30 °C) reduced early diastolic dysfunction in the J strain and altered metabolic profiles in both strains, decreasing energy expenditure and fat oxidation. The J strain specifically showed reduced respiratory exchange ratio and glucose oxidation at 30 °C. While physical activity remained constant across groups, both strains exhibited increased cardiac fibrosis and inflammatory gene expression under HFD + L-NAME, independent of housing temperature. These findings reveal strain-specific physiological adaptations to housing temperature, emphasizing the need to consider environmental conditions in heart failure research carefully.
尽管与人类相比，小鼠的代谢率和心率更高，但临床前心力衰竭研究仍严重依赖小鼠模型。本研究探讨了小鼠品系（C57BL/6J与C57BL/6N）和饲养温度（23°C与30°C）如何影响在雄性C57BL/6小鼠中使用高脂饮食加L-NAME处理建立的成熟的双打击HFpEF模型。在基线、第5周和第15周评估代谢参数和心脏功能。热中性饲养（30°C）减少了J品系的早期舒张功能障碍，并改变了两个品系的代谢谱，降低了能量消耗和脂肪氧化。J品系在30°C时特别表现出呼吸交换率和葡萄糖氧化降低。虽然各组的体力活动保持不变，但在HFD + L-NAME条件下，两个品系均表现出心脏纤维化和炎症基因表达增加，与饲养温度无关。这些发现揭示了品系特异性的对饲养温度的生理适应，强调了在心力衰竭研究中仔细考虑环境条件的必要性。
