The effect of inhibition of endoplasmic reticulum stress on lipolysis in white adipose tissue in a rat model of chronic kidney disease.
OBJECTIVE
Lipolysis in fat tissue plays an important role in the development of metabolic disturbances, a characteristic feature of chronic kidney disease (CKD). In the present study, we tested the hypothesis that the inhibition of endoplasmic reticulum (ER) stress could alleviate lipolysis in white adipose tissue in a rat model of CKD.


METHODS
A rat model of CKD was established by a method of reduced renal mass (RRM). Lipolysis was measured as the release of glycerol in ex vivo fat pads and cultured primary adipocytes. The activity of lipases and markers of ER stress were measured by Western blotting and immunoprecipitation.


RESULTS
Our data showed that lipolysis in visceral white adipose tissue was increased in RRM rats compared with control rats. In addition, increased phosphorylation of hormone-sensitive lipase (HSL) and binding of adipose triglyceride lipase (ATGL) to comparative gene identification-58 (CGI-58) protein were observed in the RRM rats. The phosphorylation of ER stress markers, including IRE1α, PERK, and eukaryotic initiation factor (eIF) 2α, and the expression of ER stress marker 78 kDa glucose-regulated protein (GRP78) were significantly increased in RRM rats. Treatment with an inhibitor of ER stress partially but significantly alleviated lipolysis, and this alleviation was accompanied by reduced binding of ATGL to CGI-58.


CONCLUSIONS
Our results showed that enhanced lipolysis and ER stress occurred in visceral white adipose tissue in a rat model of CKD. Moreover, inhibition of ER stress significantly alleviated lipolysis. These findings suggest that ER stress is a potential therapeutic target for the metabolic disturbances associated with CKD.
Division of Nephrology, Nanfang Hospital, Southern Medical University; Key Lab of Organ Failure, Ministry of Education; Guangzhou 510515, China.
Yan
Y
Zhu
Division of Nephrology, Nanfang Hospital, Southern Medical University; Key Lab of Organ Failure, Ministry of Education; Guangzhou 510515, China.
Yu-ling
YL
Chen
Division of Nephrology, Nanfang Hospital, Southern Medical University; Key Lab of Organ Failure, Ministry of Education; Guangzhou 510515, China.
Cong
C
Li
Division of Nephrology, Nanfang Hospital, Southern Medical University; Key Lab of Organ Failure, Ministry of Education; Guangzhou 510515, China.
Xiao-yan
XY
Ding
Division of Nephrology, Nanfang Hospital, Southern Medical University; Key Lab of Organ Failure, Ministry of Education; Guangzhou 510515, China.
Guo-yu
GY
Xu
Division of Nephrology, Nanfang Hospital, Southern Medical University; Key Lab of Organ Failure, Ministry of Education; Guangzhou 510515, China.
Li-li
LL
Hu
Division of Nephrology, Nanfang Hospital, Southern Medical University; Key Lab of Organ Failure, Ministry of Education; Guangzhou 510515, China.
Fan-fan
FF
Hou
Division of Nephrology, Nanfang Hospital, Southern Medical University; Key Lab of Organ Failure, Ministry of Education; Guangzhou 510515, China.
Qiu-gen
QG
Zhou
D000217:Acyltransferases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D010654:Phenylbutyrates / Q000494:pharmacology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D002787:Sterol Esterase / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism
D000217:Acyltransferases; D015852:Eukaryotic Initiation Factor-2; D005990:Glycerol; D008049:Lipase; D008565:Membrane Proteins; D010654:Phenylbutyrates; D017346:Protein Serine-Threonine Kinases; D002787:Sterol Esterase; D019892:eIF-2 Kinase; C520594:Abhd5 protein, rat; C075773:4-phenylbutyric acid; C486557:Ern2 protein, rat; C571275:PNPLA2 protein, rat