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Int J Obes (Lond). 2012 Aug;36(8):1062-71. doi: 10.1038/ijo.2011.232. Epub 2011 Dec 20.

Role of mineralocorticoid receptor/Rho/Rho-kinase pathway in obesity-related renal injury.

Author information

1
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.

Abstract

OBJECTIVE:

We examined whether aldosterone/Rho/Rho-kinase pathway contributed to obesity-associated nephropathy.

SUBJECTS:

C57BL/6J mice were fed a high fat or low fat diet, and mice on a high fat diet were treated with a mineralocorticoid receptor antagonist, eplerenone.

RESULTS:

The mice on a high fat diet not only developed obesity, but also manifested renal histological changes, including glomerular hypercellularity and increased mesangial matrix, which paralleled the increase in albuminuria. Furthermore, enhanced Rho-kinase activity was noted in kidneys from high fat diet-fed mice, as well as increased expressions of inflammatory chemokines. All of these changes were attenuated by eplerenone. In high fat diet-fed mice, mineralocorticoid receptor protein levels in the nuclear fraction and SGK1, an effector of aldosterone, were upregulated in kidneys, although serum aldosterone levels were unaltered. Furthermore, aldosterone and 3β-hydroxysteroid dehydrogenase in renal tissues were upregulated in high fat diet-fed mice. Finally, in cultured mesangial cells, stimulation with aldosterone enhanced Rho-kinase activity, and pre-incubation with eplerenone prevented the aldosterone-induced activation of Rho kinase.

CONCLUSION:

Excess fat intake causes obesity and renal injury in C57BL/6J mice, and these changes are mediated by an enhanced mineralocorticoid receptor/Rho/Rho-kinase pathway and inflammatory process. Mineralocorticoid receptor activation in the kidney tissue and the subsequent Rho-kinase stimulation are likely to participate in the development of obesity-associated nephropathy without elevation in serum aldosterone levels.

PMID:
22184057
PMCID:
PMC3419977
DOI:
10.1038/ijo.2011.232
[Indexed for MEDLINE]
Free PMC Article

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