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Updated: Jun 28, 2026
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Structural and functional changes in the kidneys of high-fat diet-induced obese mice
Naoko Deji1, Shinji Kume, Shin-Ichi Araki
1Dept. of Medicine, Shiga Univ. of Medical Science, Seta, Otsu, Shiga 520-2192, Japan.
Abstract:
Metabolic syndrome has been reported to be associated with chronic kidney disease, but the mechanisms remain unclear. Although feeding of a high-fat diet (HFD) to C57BL/6 mice is reported to induce systemic metabolic abnormalities and subsequent renal injuries, such as albuminuria, similar to human metabolic syndrome, alterations in HFD-induced renal injuries have not been fully elucidated in detail. We therefore investigated the structural and functional changes in the kidneys of C57BL/6 mice on a HFD. Six-week-old mice were fed a low-fat diet (LFD; 10% of total calories from fat) or a HFD (60% fat) for 12 wk. Mice fed a HFD showed significant increases in body weight, systolic blood pressure, plasma insulin, glucose, and triglycerides compared with those on a LFD. Accompanying these systemic changes, mice on a HFD showed albuminuria, an increase in glomerular tuft area, and mesangial expansion. These systemic and renal alterations in mice on a HFD were prevented by body weight control with the dietary restriction of feeding a HFD. Furthermore, mice on a HFD showed renal pathophysiological alterations including renal lipid accumulation, an increased accumulation of type IV collagen in glomeruli, an increase in macrophage infiltration in the renal medulla, an increase in urinary 8-hydroxy-2'-deoxyguanosine excretion, and impaired sodium handling. In conclusion, this study suggests that local metabolic alterations in the kidney play important roles in the development of renal injury associated with metabolic syndrome in addition to systemic metabolic changes and an increase in body weight.
Insights
High-fat diets induce kidney damage and metabolic syndrome in mice, characterized by albuminuria and impaired kidney function. Controlling body weight prevents these harmful effects, highlighting the kidney
Area of Science:
- Nephrology
- Metabolic Diseases
- Animal Models
Background:
- Metabolic syndrome is linked to chronic kidney disease, but underlying mechanisms are not fully understood.
- High-fat diets (HFD) in mice mimic human metabolic syndrome, causing systemic abnormalities and kidney injury, yet detailed renal changes require further elucidation.
Purpose of the Study:
- To investigate the detailed structural and functional kidney alterations in C57BL/6 mice fed a high-fat diet (HFD).
Main Methods:
- Six-week-old C57BL/6 mice were fed either a low-fat diet (LFD) or a HFD (60% fat) for 12 weeks.
- Evaluated systemic parameters (body weight, blood pressure, plasma insulin, glucose, triglycerides) and renal markers (albuminuria, glomerular changes, lipid accumulation, collagen IV, macrophages, oxidative stress, sodium handling).
Main Results:
- HFD-fed mice exhibited increased body weight, blood pressure, plasma insulin, glucose, and triglycerides compared to LFD-fed mice.
- Renal changes included albuminuria, glomerular hypertrophy, mesangial expansion, renal lipid accumulation, increased glomerular type IV collagen, macrophage infiltration, elevated urinary 8-hydroxy-2'-deoxyguanosine, and impaired sodium handling.
- Body weight control via dietary restriction prevented these systemic and renal alterations.
Conclusions:
- High-fat diet-induced metabolic syndrome in mice leads to significant systemic and renal pathological changes.
- Local metabolic alterations within the kidney contribute to renal injury in metabolic syndrome, alongside systemic changes and increased body weight.
- Weight management is crucial in mitigating HFD-induced kidney damage.
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