title: Structural and functional changes in the kidneys of high-fat diet-induced obese mice.
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.
authors.affiliation: Dept. of Medicine, Shiga Univ. of Medical Science, Seta, Otsu, Shiga 520-2192, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Deji
authors.forename: Shinji
authors.initials: S
authors.lastname: Kume
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Araki
authors.forename: Mariko
authors.initials: M
authors.lastname: Soumura
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Keiji
authors.initials: K
authors.lastname: Isshiki
authors.forename: Masami
authors.initials: M
authors.lastname: Chin-Kanasaki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koya
authors.forename: Masakazu
authors.initials: M
authors.lastname: Haneda
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Takashi
authors.initials: T
authors.lastname: Uzu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D024141:Collagen Type IV / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D012964:Sodium / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D024141:Collagen Type IV; D004041:Dietary Fats; D007328:Insulin; D012964:Sodium