Obesity has increased dramatically during the past decade and is an established risk factor for the development of chronic kidney disease. In this study we focused our attention on the potential dysregulation of renal aquaporins (AQPs) in the kidney of a mouse model of obesity and type 2 diabetes mellitus. Mice were fed a high fat (HFD) or normal (ND) diet and analyzed at 20 weeks and at 34 weeks. At 20 weeks, western blotting of total lysates from HFD mice revealed higher immunoreactivity for AQP1 whereas no significant change in AQP2, AQP3 and AQP4 abundance was observed. However, AQP1, AQP2, AQP3 and AQP4 immunoreactivity decreased in a crude kidney membrane preparation suggesting a reduced cell surface expression of all these AQPs. Stopped flow light scattering studies showed a reduced osmotic water permeability (Pf) of the whole renal plasma membranes from 254.8±30.5 mm/s to 169.8±16.2 (P<0.0001) in ND versus HFD mice, respectively, consistent with the observed decrease in AQPs cell surface expression. At 34 weeks, western blotting of total lysates or of a crude membrane preparation from HFD mice revealed significant downregulation of AQP1 and AQP2 whereas AQP3 and AQP4 immunoreactivity was unchanged in both preparations compared to ND mice. Altogether, these data reveal altered AQPs expression and osmotic water permeability of HFD mice kidney. These observations suggest a patho-physiological relevance for aquaporins in renal complications associated with metabolic syndrome.

Renal aquaporin expression and osmotic water permeability is altered in mice fed a high fat diet

TAMMA, GRAZIA;Gena P;RANIERI, MARIANNA;SVELTO, Maria;CALAMITA, Giuseppe;VALENTI, Giovanna
2011

Abstract

Obesity has increased dramatically during the past decade and is an established risk factor for the development of chronic kidney disease. In this study we focused our attention on the potential dysregulation of renal aquaporins (AQPs) in the kidney of a mouse model of obesity and type 2 diabetes mellitus. Mice were fed a high fat (HFD) or normal (ND) diet and analyzed at 20 weeks and at 34 weeks. At 20 weeks, western blotting of total lysates from HFD mice revealed higher immunoreactivity for AQP1 whereas no significant change in AQP2, AQP3 and AQP4 abundance was observed. However, AQP1, AQP2, AQP3 and AQP4 immunoreactivity decreased in a crude kidney membrane preparation suggesting a reduced cell surface expression of all these AQPs. Stopped flow light scattering studies showed a reduced osmotic water permeability (Pf) of the whole renal plasma membranes from 254.8±30.5 mm/s to 169.8±16.2 (P<0.0001) in ND versus HFD mice, respectively, consistent with the observed decrease in AQPs cell surface expression. At 34 weeks, western blotting of total lysates or of a crude membrane preparation from HFD mice revealed significant downregulation of AQP1 and AQP2 whereas AQP3 and AQP4 immunoreactivity was unchanged in both preparations compared to ND mice. Altogether, these data reveal altered AQPs expression and osmotic water permeability of HFD mice kidney. These observations suggest a patho-physiological relevance for aquaporins in renal complications associated with metabolic syndrome.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/128067
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