Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKD

Overview

Journal J Am Soc Nephrol

Specialty Nephrology

Date 2017 Sep 2

PMID 28860163

Citations 53

Authors

Shiran Udi

Liad Hinden

Brian Earley

Adi Drori

Noa Reuveni

Rivka Hadar

Resat Cinar

Alina Nemirovski

Joseph Tam

Affiliations

Soon will be listed here.

Abstract

Obesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CBR) induces nephropathy, whereas CBR blockade improves kidney function. Whether these effects are mediated a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CBR in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis. These effects associated with increased activation of liver kinase B1 and the energy sensor AMP-activated protein kinase, as well as enhanced fatty acid -oxidation. Collectively, these findings indicate that renal proximal tubule cell CBR contributes to the pathogenesis of obesity-induced renal lipotoxicity and nephropathy by regulating the liver kinase B1/AMP-activated protein kinase signaling pathway.

Citing Articles

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