Proximal tubular cannabinoid-1 receptor regulates obesity-induced CKD

Shiran Udi, Liad Hinden, Brian Earley, Adi Drori, Noa Reuveni, Rivka Hadar, Resat Cinar, Alina Nemirovski, Joseph Tam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

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 (CB1R) induces nephropathy, whereas CB1R blockade improves kidney function. Whether these effects aremediated via a specific cell typewithin the kidney remains unknown.Here, we showthat specific deletion of CB1R 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 associatedwith increased activation of liver kinase B1 and the energy sensor AMPactivated protein kinase, as well as enhanced fatty acid b-oxidation. Collectively, these findings indicate that renal proximal tubule cell CB1R contributes to the pathogenesis of obesity-induced renal lipotoxicity and nephropathy by regulating the liver kinase B1/AMP-activated protein kinase signaling pathway.

Original languageAmerican English
Pages (from-to)3518-3532
Number of pages15
JournalJournal of the American Society of Nephrology : JASN
Volume28
Issue number12
DOIs
StatePublished - Dec 2017

Bibliographical note

Funding Information:
This work was supported by the German-Israeli Foundation grant (no. I-2345-201.2/2014), and an European Research Council (ERC)-2015-Starting Grant (no. 676841) to J.T.

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