Document Detail


Dietary fructose causes tubulointerstitial injury in the normal rat kidney.
MedLine Citation:
PMID:  20071464     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Takahiro Nakayama; Tomoki Kosugi; Michael Gersch; Thomas Connor; Laura Gabriela Sanchez-Lozada; Miguel A Lanaspa; Carlos Roncal; Santos E Perez-Pozo; Richard J Johnson; Takahiko Nakagawa
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2010-01-13
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  298     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-25     Completed Date:  2010-03-19     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F712-20     Citation Subset:  IM    
Affiliation:
Division of Nephrology, University of Florida, Gainesville, Florida, USA.
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism
Animals
Cell Proliferation / drug effects*
Cells, Cultured
Collagen / metabolism
Dietary Sucrose / metabolism,  toxicity*
Fibroblasts / drug effects,  metabolism,  pathology
Fructokinases / metabolism
Fructose / metabolism,  toxicity*
Glucose / pharmacology*
Glucose Transporter Type 2 / metabolism
Glucose Transporter Type 5 / metabolism
Hyperplasia
Kidney Diseases / etiology*,  metabolism,  pathology
Kidney Tubules, Proximal / drug effects*,  metabolism,  pathology
Macrophages / drug effects,  pathology
Male
Organ Size
Rats
Rats, Sprague-Dawley
Severity of Illness Index
Time Factors
Grant Support
ID/Acronym/Agency:
R01 HL-68607-01/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Actins; 0/Dietary Sucrose; 0/Glucose Transporter Type 2; 0/Glucose Transporter Type 5; 0/Slc2a2 protein, rat; 0/Slc2a5 protein, rat; 0/smooth muscle actin, rat; 30237-26-4/Fructose; 50-99-7/Glucose; 9007-34-5/Collagen; EC 2.7.1.-/Fructokinases; EC 2.7.1.3/ketohexokinase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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