Centre for Cardiovascular Biology and Disease Research, Department of Microbiology, Anatomy Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC, Australia.
Department of Animal, Plant and Soil Sciences, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC, Australia.
Sci Rep. 2023 Dec 8;13(1):21644. doi: 10.1038/s41598-023-47903-1.
Obesity and vascular dysfunction are independent and sexually dimorphic risk factors for cardiovascular disease. A high fat diet (HFD) is often used to model obesity in mice, but the sex-specific effects of this diet on aortic inflammation and function are unclear. Therefore, we characterized the aortic immune cell profile and function in 6-week-old male and female C57BL/6 mice fed a normal chow diet (NCD) or HFD for 10 weeks. Metabolic parameters were measured weekly and fortnightly. At end point, aortic immune cell populations and endothelial function were characterized using flow cytometry and wire myography. HFD-male mice had higher bodyweight, blood cholesterol, fasting blood glucose and plasma insulin levels than NCD mice (P < 0.05). HFD did not alter systolic blood pressure (SBP), glycated hemoglobin or blood triglycerides in either sex. HFD-females had delayed increases in bodyweight with a transient increase in fasting blood glucose at week 8 (P < 0.05). Flow cytometry revealed fewer proinflammatory aortic monocytes in females fed a HFD compared to NCD. HFD did not affect aortic leukocyte populations in males. Conversely, HFD impaired endothelium-dependent vasorelaxation, but only in males. Overall, this highlights biological sex as a key factor determining vascular disease severity in HFD-fed mice.
肥胖和血管功能障碍是心血管疾病的独立且存在性别差异的危险因素。高脂肪饮食（HFD）常用于在小鼠中模拟肥胖，但这种饮食对主动脉炎症和功能的性别特异性影响尚不清楚。因此，我们对 6 周龄雄性和雌性 C57BL/6 小鼠进行了研究，这些小鼠分别喂食正常饮食（NCD）或 HFD 10 周。每周和每两周测量代谢参数。在终点时，使用流式细胞术和线描术对主动脉免疫细胞群和内皮功能进行了表征。与 NCD 组相比，HFD 组雄性小鼠的体重、血胆固醇、空腹血糖和血浆胰岛素水平更高（P<0.05）。HFD 对雄性的收缩压（SBP）、糖化血红蛋白或血液甘油三酯均无影响。与 NCD 组相比，HFD 组雌性的体重增加延迟，在第 8 周时出现空腹血糖一过性升高（P<0.05）。流式细胞术显示，与 NCD 组相比，HFD 组雌性主动脉中的促炎单核细胞数量较少。HFD 对雄性的主动脉白细胞群没有影响。相反，HFD 损害了雄性的内皮依赖性血管舒张功能。总的来说，这凸显了生物学性别是决定 HFD 喂养小鼠血管疾病严重程度的关键因素。
