Dietary fructose causes tubulointerstitial injury in the normal rat kidney.
Recent studies suggest that the metabolic syndrome is associated with renal disease. We previously reported that a high-fructose diet, but not a high-glucose diet, can induce metabolic syndrome and accelerate chronic renal disease in rats. We now examined the effects of a high-fructose diet on normal rat kidneys. Three groups of Sprague-Dawley rats were pair fed a special diet containing 60% fructose, 60% glucose, or control standard rat chow for 6 wk, and then histological studies were performed. The effect of fructose to induce cell proliferation in cultured proximal tubular cells was also performed. Fructose diet, but not glucose diet, significantly increased kidney weight by 6 wk. The primary finding was tubular hyperplasia and proliferation involving all segments of the proximal tubules while glomerular changes were not observed. This is the same site where the fructose transporters (GLUT2 and -5) as well as the key enzyme in fructose metabolism (ketohexokinase) were expressed. Consistently, fructose also induced proliferation of rat proximal tubular cells in culture. In vivo, tubular proliferation was also associated with focal tubular injury, with type III collagen deposition in the interstitium, an increase in alpha-smooth muscle actin positive myofibroblasts, and an increase in macrophage infiltration. In conclusion, a high-fructose diet induces cell proliferation and hyperplasia in proximal tubules, perhaps via a direct metabolic effect. The effect is independent of total energy intake and is associated with focal tubulointerstitial injury. These studies may provide a mechanism by which metabolic syndrome causes renal disease.
Nakayama
Takahiro
T
Division of Nephrology, University of Florida, Gainesville, Florida, USA.
Kosugi
Tomoki
T
Gersch
Michael
M
Connor
Thomas
T
Sanchez-Lozada
Laura Gabriela
LG
Lanaspa
Miguel A
MA
Roncal
Carlos
C
Perez-Pozo
Santos E
SE
Johnson
Richard J
RJ
Nakagawa
Takahiko
T
D000199:Actins / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D019422:Dietary Sucrose / Q000378:metabolism / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005631:Fructokinases / Q000378:metabolism; D005632:Fructose / Q000378:metabolism / Q000633:toxicity*; D005947:Glucose / Q000494:pharmacology*; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D051296:Glucose Transporter Type 5 / Q000378:metabolism; D006965:Hyperplasia; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors
D000199:Actins; D003094:Collagen; D019422:Dietary Sucrose; D005631:Fructokinases; D005632:Fructose; D005947:Glucose; D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; C495683:Slc2a2 protein, rat; C495727:Slc2a5 protein, rat; C498862:Acta2 protein, rat; C021475:ketohexokinase