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Leptin induces rat glomerular mesangial cell hypertrophy, but does not regulate hyperplasia or apoptosis

International Journal of Obesity volume 29, pages 1395–1401 (2005)Cite this article

Abstract

OBJECTIVE:

There is an increased incidence of renal glomerulosclerosis in obese individuals. One of the major structural changes observed in nephropathy is the increase in kidney size, which may occur due to hypertrophy or changes in the rate of hyperplasia or apoptosis. Here we investigated whether leptin, the product of the obese (ob) gene which is found at high plasma levels in obese and diabetic individuals, alters any of these parameters.

RESULTS:

We show that leptin increased hypertrophy of these cells. This was indicated by an approximately 33% increase in cell size and 40% increase in leucine incorporation. Furthermore, we show that the hypertrophic effect of leptin was mediated via PI 3-kinase and ERK1/2 by using the inhibitors LY294002 and PD98059, respectively. We also confirm that leptin activates both PI 3-kinase and ERK1/2 in these cells. We show that hyperplasia was not affected by leptin by measuring rat glomerular mesangial cell number and by assessing bromodeoxyuridine uptake. Leptin also did not alter caspase 3-like activity under control conditions or upon induction of apoptosis by ultraviolet light, suggesting that apoptosis was not regulated by leptin in these cells.

CONCLUSION:

Our results show that leptin induced glomerular mesangial cell hypertrophy via PI 3-kinase and ERK1/2, and that hyperplasia and apoptosis were not altered by leptin. The hypertrophic effect of leptin may play a role in the pathophysiology of nephropathy associated with obesity.

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Acknowledgements

GS thanks the Canadian Diabetes Association for funding via a scholarship in honor of the late Mary A Bodington. DO conducted this work during a Natural Sciences and Engineering Research Council of Canada (NSERC) summer studentship. GS also acknowledges support of the Ontario Ministry of Economic Development and Trade via a Premiers Research Excellence Award. Funding from the Canada Foundation for Innovation and Ontario Innovation Trust is also acknowledged. We also thank George Bikopoulos, Rolando Ceddia and Dominika Sekula for contributions during the preparation of this manuscript.

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  1. Department of Biology, York University, Toronto, Canada

    M P-S Lee, D Orlov & G Sweeney

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  1. M P-S Lee
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  2. D Orlov
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  3. G Sweeney
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Correspondence to G Sweeney.

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Lee, MS., Orlov, D. & Sweeney, G. Leptin induces rat glomerular mesangial cell hypertrophy, but does not regulate hyperplasia or apoptosis. Int J Obes 29, 1395–1401 (2005). https://doi.org/10.1038/sj.ijo.0803031

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