From the Department of Pharmacology and Toxicology, Michigan State University, East Lansing (R.F., H.G., J.J.G., G.D.F., H.X.).
Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing (J.R.H.).
Hypertension. 2018 Nov;72(5):e43-e52. doi: 10.1161/HYPERTENSIONAHA.118.11485.
We examined the impact of sex on high-fat diet (HFD)-induced renal alterations in Dahl salt-sensitive and Sprague Dawley rats. In Dahl rats, HFD (60% kcal from fat for 24-26 weeks starting at weaning) significantly and equally increased blood pressure in males and females when compared with rats fed a control diet (10% kcal from fat). Male Dahl rats on HFD exhibited progressive renal histological injury and moderately increased renal macrophage infiltration at 10 and 24 weeks of feeding when compared with males on control diet. Female Dahl rats had lower grade renal injury and less macrophage infiltration (except at 17 weeks) than males regardless of diet. Male Dahl rats on both diets showed progressively increasing numbers of renal T-cells, a pattern not observed in females. HFD per se did not significantly affect renal T-cell number. Male Dahl rats had lower renal regulatory T-cells cell ratio than females at 24 weeks. Renal macrophage and T-cell infiltrations were highly correlated to final mean arterial pressure levels in males but not in females. Sprague Dawley rats fed HFD were normotensive without significant renal injury/inflammation after 24 weeks of feeding. In summary, HFD feeding fails to increase arterial blood pressure in Sprague Dawley rats but strongly promotes hypertension in both male and female Dahl salt-sensitive rats. Only Dahl males, however, exhibited blood pressure-associated renal inflammation and injury. Maintenance of regulatory T-cells ratio may protect against hypertension-associated renal injury/inflammation but not HFD-induced hypertension.
我们研究了性别对高脂肪饮食（HFD）诱导的达尔盐敏感型和斯普拉格道利大鼠肾脏改变的影响。在达尔大鼠中，高脂肪饮食（从脂肪中摄取 60%的热量，从断奶开始持续 24-26 周）与喂食对照饮食（从脂肪中摄取 10%的热量）的大鼠相比，显著且同等地增加了雄性和雌性大鼠的血压。与喂食对照饮食的雄性大鼠相比，喂食 HFD 的雄性达尔大鼠在 10 和 24 周的喂养时表现出进行性的肾脏组织损伤和中度增加的肾脏巨噬细胞浸润。无论饮食如何，雌性达尔大鼠的肾脏损伤程度较低，巨噬细胞浸润较少（17 周时除外）。无论饮食如何，雄性达尔大鼠的肾脏 T 细胞数量都逐渐增加，而雌性大鼠则没有观察到这种模式。HFD 本身并没有显著影响肾脏 T 细胞的数量。在 24 周时，雄性达尔大鼠的肾脏调节性 T 细胞比例低于雌性大鼠。雄性大鼠的肾脏巨噬细胞和 T 细胞浸润与终末平均动脉压水平高度相关，但雌性大鼠则不然。24 周喂养高脂肪饮食的斯普拉格道利大鼠血压正常，无明显肾脏损伤/炎症。总之，HFD 喂养不会增加斯普拉格道利大鼠的动脉血压，但会强烈促进雄性和雌性达尔盐敏感型大鼠的高血压。然而，只有达尔雄性大鼠表现出血压相关的肾脏炎症和损伤。维持调节性 T 细胞比例可能有助于预防高血压相关的肾脏损伤/炎症，但不能预防 HFD 引起的高血压。
