title: Diet induced obesity in rats reduces NHE3 and Na(+) /K(+) -ATPase expression in the kidney.
abstract: The consumption of a high fat diet (HFD) is associated with proteinuria and altered sodium handling and excretion, which can lead to kidney disease. In the proximal tubule, the Na(+) /H(+) Exchanger 3 (NHE3) is responsible for normal protein reabsorption and the reabsorption of approximately 70% of the renal sodium load. It is the Na(+) /K(+) -ATPase that provides the driving force for the reabsorption of sodium and its exit across the basolateral membrane. This study investigates the effects that consumption of a HFD for 12 weeks has on NHE3 and Na(+) /K(+) -ATPase expression in the kidney. Western blot analysis identified a significant reduction in NHE3 and its modulator, phosphorylated protein kinase B, in renal lysate from obese rats. In the obese rats, a reduction in NHE3 expression in the proximal tubule may impact on the acidification of endosomes which are responsible for albumin uptake, suggesting a key role for the exchanger in protein endocytosis in obesity. Western blot analysis identified a reduction in Na(+) /K(+) -ATPase which could also potentially impact on albumin uptake and sodium reabsorption. This study demonstrates that consumption of a HFD for 12 weeks reduces renal NHE3 and Na(+) /K(+) -ATPase expression, an effect that may contribute to the albuminuria associated with obesity. Furthermore the reduction in these transporters is not likely to contribute to the reduced sodium excretion in obesity. These data highlight a potential link between NHE3 and Na(+) /K(+) -ATPase in the pathophysiological changes in renal protein handling observed in obesity.
authors.affiliation: Centre for Chronic Disease Prevention and Management, College of Health and Biomedicine, Victoria University, St Albans, Victoria, Australia.|Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: J F
authors.initials: JF
authors.lastname: Briffa
authors.affiliation: Centre for Chronic Disease Prevention and Management, College of Health and Biomedicine, Victoria University, St Albans, Victoria, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Grinfeld
authors.affiliation: Centre for Chronic Disease Prevention and Management, College of Health and Biomedicine, Victoria University, St Albans, Victoria, Australia.
authors.forename: K A
authors.initials: KA
authors.lastname: Jenkin
authors.affiliation: Centre for Chronic Disease Prevention and Management, College of Health and Biomedicine, Victoria University, St Albans, Victoria, Australia.
authors.forename: M L
authors.initials: ML
authors.lastname: Mathai
authors.affiliation: Department of Physiology, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Poronnik
authors.affiliation: Centre for Chronic Disease Prevention and Management, College of Health and Biomedicine, Victoria University, St Albans, Victoria, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: McAinch
authors.affiliation: Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: D H
authors.initials: DH
authors.lastname: Hryciw
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D015971:Gene Expression Regulation, Enzymologic; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000150:complications / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011507:Proteinuria / Q000150:complications; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D051057:Proto-Oncogene Proteins c-akt; D000254:Sodium-Potassium-Exchanging ATPase
keywords: AKT; NHE3; Na+/K+-ATPase; obesity; proteinuria