Effects of hydrophilic statins on renal tubular lipid accumulation in diet-induced obese mice.
Animal models of obesity show that lipid deposits can injure the kidneys,and there is evidence for the role of lipids in the development of chronic renal dis-ease (CKD). Statins exhibit a lipid-lowering effect that acts on both total cholesterol and triglyceride (TG) levels and pleiotropic effects including their ability to reduce inflammation and fibrosis. The purpose of the present study was to confirm whether obesity induced by a high-fat diet (HFD, 60% fat) promotes lipid accumulation in the tubulointerstitial and/or glomerular areas in the kidney, and whether treatment of several statins, pravastatin (30 mg/kg, p.o.), rosuvastatin (3 mg/kg, p.o.),pitavastatin (1 mg/kg, p.o.) and atorvastatin (10 mg/kg, p.o.), suppresses obesity-induced lipid accumulation. Using male C57Bl/6J mice, we examined parameters related to energy metabolism, lipid accumulation as well as macrophage infiltration in glomeruli and the tubulointerstitial area, and glomerular injury using nephrin and desmin expression. None of the statins affected body weight, glucose metabolism,serum TG and adiponectin levels, or serum inflammatory cytokine levels. However,all statins improved lipid accumulation in the proximal tubules, improved glomerular hypertrophy, increased nephrin expression and decreased desmin expression, compared to non-treated obese animals. Moreover, the reduction of proximal tubular lipid accumulation was greater with pravastatin and rosuvastatin treatment than with pitavastatin and atorvastatin treatment. We concluded that hydrophilic statins may be more effective for preventing lipid accumulation in renal tubules than lipophilic statins.
Koro
K
Gotoh
Takayuki
T
Masaki
Seiichi
S
Chiba
Hisae
H
Ando
Kansuke
K
Fujiwara
Takanobu
T
Shimasaki
Yasuko
Y
Tawara
Ikuko
I
Toyooka
Kentaro
K
Shiraishi
Kimihiko
K
Mitsutomi
Manabu
M
Anai
Emi
E
Itateyama
Junji
J
Hiraoka
Kohei
K
Aoki
Naoya
N
Fukunaga
Tomoko
T
Nawata
Tetsuya
T
Kakuma
D052242:Adiponectin / Q000097:blood; D000818:Animals; D000069059:Atorvastatin; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology; D007684:Kidney Tubules / Q000187:drug effects* / Q000503:physiopathology; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology*; D017035:Pravastatin / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D011804:Quinolines; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin; D017035:Pravastatin; C108475:pitavastatin