TY - JOUR
T1 - Proximal tubular cannabinoid-1 receptor regulates obesity-induced CKD
AU - Udi, Shiran
AU - Hinden, Liad
AU - Earley, Brian
AU - Drori, Adi
AU - Reuveni, Noa
AU - Hadar, Rivka
AU - Cinar, Resat
AU - Nemirovski, Alina
AU - Tam, Joseph
N1 - 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.
PY - 2017/12
Y1 - 2017/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85038413447&partnerID=8YFLogxK
U2 - 10.1681/ASN.2016101085
DO - 10.1681/ASN.2016101085
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C2 - 28860163
AN - SCOPUS:85038413447
SN - 1046-6673
VL - 28
SP - 3518
EP - 3532
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 12
ER -
