Lois Q Balugo Jamie Lynne, Samuels Joshua D, Milstein Joshua L, Jansen Maurits A, Harris Thurl E, Culver Silas A
Division of Endocrinology, Department of Medicine, University of Virginia Health System, 450 Ray C. Hunt Dr, Charlottesville, VA, 22903, USA.
Department of Neuroscience, University of Virginia Health System, 409 Lane Rd, Charlottesville, VA, 22908, USA.
Biochem Biophys Res Commun. 2025 May 5;762:151765. doi: 10.1016/j.bbrc.2025.151765. Epub 2025 Apr 5.
Renal cortical lipid content is increased in obesity and contributes to obesity-related kidney dysfunction. Studying this phenomenon requires reliable tools to quantitate renal cortical lipid in preclinical models. However, most current preclinical methods require euthanizing the model. MRI has been used to measure lipid content in other organ systems but, to our knowledge, has not been employed in quantifying kidney lipid in mice. Eleven-week old male C57BL/6 mice were fed either standard chow (ND) (12 % fat) or high fat diet (HFD) (45 % fat) for 12 weeks. At the end of this period, a 9.4 T Bruker MRI was utilized to perform fat-water separation imaging based on the Dixon method. These images were utilized to calculate a proton-density fat fraction for regions of interest within the renal cortex. For validation, frozen kidney sections underwent immunofluorescent LipidSpot™ staining for quantitation of lipid droplet area. After 12 weeks on diet, the average body weight of HFD fed mice was 34.63g compared to 27.84g in ND controls (p < 0.001). Consistent with prior studies, MRI demonstrated increased hepatic fat content of 13.34 % in HFD fed mice compared to 8.3 % in ND controls (p < 0.05). Renal cortical lipid measured by MRI averaged 7.35 % in HFD fed mice compared to 4.75 % in ND controls (p < 0.05). On histologic analysis, HFD fed mice had a ratio of lipid droplet area to DAPI of 0.866 compared to 0.221 in ND fed mice (p < 0.05). These results demonstrate that MRI can be used effectively to measure changes in renal cortical lipid content in mice.
肥胖时肾皮质脂质含量增加，并导致与肥胖相关的肾功能障碍。研究这一现象需要可靠的工具来定量临床前模型中的肾皮质脂质。然而，目前大多数临床前方法都需要处死模型。磁共振成像（MRI）已被用于测量其他器官系统中的脂质含量，但据我们所知，尚未用于定量小鼠肾脏脂质。将11周龄雄性C57BL/6小鼠分为两组，分别喂食标准饲料（ND）（脂肪含量12%）或高脂饮食（HFD）（脂肪含量45%），持续12周。在此期间结束时，使用9.4T布鲁克MRI基于狄克逊方法进行脂肪-水分离成像。利用这些图像计算肾皮质内感兴趣区域的质子密度脂肪分数。为了进行验证，对冷冻的肾脏切片进行免疫荧光LipidSpot™ 染色以定量脂滴面积。饮食12周后，高脂饮食喂养小鼠的平均体重为34.63g，而正常饮食对照组为27.84g（p<0.001）。与先前的研究一致，MRI显示高脂饮食喂养小鼠的肝脏脂肪含量增加至13.34%，而正常饮食对照组为8.3%（p<0.05）。通过MRI测量，高脂饮食喂养小鼠的肾皮质脂质平均为7.35%，而正常饮食对照组为4.75%（p<0.05）。组织学分析显示，高脂饮食喂养小鼠的脂滴面积与DAPI的比值为0.866，而正常饮食喂养小鼠为0.221（p<0.05）。这些结果表明，MRI可有效用于测量小鼠肾皮质脂质含量的变化。
