Obesidad

Genes Nutr DOI 10.1007/s12263-012-0295-5

REVIEW

The role of nuclear receptors in the kidney in obesity and metabolic syndrome
Claudia Tovar-Palacio • Nimbe Torres • ˜ Andrea Diaz-Villasenor • Armando R. Tovar

Received: 13 February 2012 / Accepted: 2 April 2012 Ó Springer-Verlag 2012

Abstract Nuclear receptors are ligand-activated transcriptional regulators of several key aspects ofrenal physiology and pathophysiology. As such, nuclear receptors control a large variety of metabolic processes, including kidney lipid metabolism, drug clearance, inflammation, fibrosis, cell differentiation, and oxidative stress. Derangement of nuclear receptor regulation, that is, mainly due to obesity may induce metabolic syndrome, may contribute to the pathogenesis and progression of chronicrenal disease and may result in end-stage renal disease. This places nuclear receptors at the forefront of novel therapeutic approaches for a broad range of kidney disorders and diseases, including glomerulosclerosis, tubulointerstitial disease, renal lipotoxicity, kidney fibrosis, and hypertension. This review focuses on the importance of the transcription factors peroxisome proliferator-activatedreceptor alpha, peroxisome proliferator-activated receptor beta, peroxisome proliferator-activated receptor gamma, liver X receptors, farnesoid X receptor, and the pregnane X receptor/steroid and xenobiotic receptor (PXR) on the physiology and pathophysiology of renal diseases associated with obesity and metabolic syndrome.

Keywords Kidney Á Nuclear receptors Á Obesity Á Metabolic syndromeThe role of nuclear receptors in kidney disease Due to the consumption of a Western-style diet and a sedentary lifestyle, obesity is rapidly becoming the most important health problem challenging developed and nondeveloped countries. Although obesity is often associated with diabetes and hypertension, which are the two most common risk factors for the development of end-stage renal disease,obesity has been suggested as an independent risk factor for the development of chronic kidney disease (Praga and Morales 2006; Rutkowski et al. 2006; Wahba and Mak 2007; Wang et al. 2008). Early in the course of obesity, structural and functional changes similar to diabetic kidney disease occur (Henegar et al. 2001). These changes, considered to be precursors to more severe renal injury, includeglomerular hyperfiltration, glomerular basement membrane thickening, mesangial cell proliferation, mesangial matrix thickening, and expansion of the Bowman’s capsule. Morbid obesity has been associated with the eventual development of focal and segmental glomerulosclerosis even in the absence of diabetes (Kambham et al. 2001; Praga 2002). Studies in humans and in animal models have reported thataccumulation of lipids in the kidney has been shown to promote renal disease (Kimmelstiel and Wilson 1936; Wilens and Elster 1950; Proctor et al. 2006; Jiang et al. 2005; Tovar-Palacio et al. 2011). Heavy glomerular proteinuria (nephritic syndrome) is associated with hyperlipidemia, lipiduria, and progressive kidney disease. Glomerular and tubular epithelial cells in the nephritic kidney are exposedto large quantities of lipids bound to filtered proteins, the uptake of which raises cellular lipids.

C. Tovar-Palacio (&) Department of Nephrology and Mineral Metabolism, National Medical Science and Nutrition Institute, ´ Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan, 14000 Mexico, D.F., Mexico e-mail: tovarpal@gmail.com ˜ N. Torres Á A. Diaz-Villasenor Á A. R. Tovar Department ofNutrition Physiology, National Medical Science ´ and Nutrition Institute, Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan, 14000 Mexico, D.F., Mexico

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Cellular lipid homeostasis is regulated by the influx, synthesis, and efflux of lipids (Kim et al. 2009). The accumulation of triglycerides and cholesterol in the kidney is mediated by increased expression and activity of the...