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J Am Soc Nephrol. 2017 Dec;28(12):3518-3532. doi: 10.1681/ASN.2016101085. Epub 2017 Aug 31.

Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKD.

Author information

1
Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
2
Laboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.
3
Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel; yossit@ekmd.huji.ac.il.

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 are mediated via a specific cell type within the kidney remains unknown. Here, we show that 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 associated with increased activation of liver kinase B1 and the energy sensor AMP-activated protein kinase, as well as enhanced fatty acid β-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.

KEYWORDS:

AMPK; CB1 receptor; Endocannabinoids; Renal Proximal Tubular Cell; chronic kidney disease; obesity

Comment in

PMID:
28860163
PMCID:
PMC5698062
DOI:
10.1681/ASN.2016101085
[Indexed for MEDLINE]
Free PMC Article

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