Exenatide reduces cardiomyocyte apoptosis by stimulating adiponectin secretion and activating APPL1-AMPK-PPARα axis

Xiaotian Lei; Qinan Wu; Weiling Leng; Minxia Wu; Liu Chen; Ziwen Liang

doi:10.21037/atm.2019.06.17

Exenatide reduces cardiomyocyte apoptosis by stimulating adiponectin secretion and activating APPL1-AMPK-PPARα axis

Ann Transl Med. 2019 Jul;7(14):326. doi: 10.21037/atm.2019.06.17.

Authors

Xiaotian Lei¹, Qinan Wu², Weiling Leng¹, Minxia Wu³, Liu Chen¹, Ziwen Liang¹

Affiliations

¹ Department of Endocrinology, Southwest Hospital, the Third Military Medical University (Army Medical University), Chongqing 400038, China.
² Department of Endocrine Nephropathy, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400038, China.
³ Health Management Center, Southwest Hospital, the Third Military Medical University (Army Medical University), Chongqing 400038, China.

Abstract

Background: To explore the mechanism that exenatide reduces cardiomyocyte apoptosis via the adiponectin pathway in vitro.

Methods: Cardiomyocytes were randomly divided into the control group (group C), diabetic group (group D), diabetic + exenatide treatment group (group DE), diabetic + exenatide treatment + APPL1 overexpression group (group OE), and diabetic + exenatide treatment + APPL1 knock-down group (group KD). After 48 h culture, the apoptosis rate, the adiponectin level in the cell culture fluid, and the expression levels of APPL1, p-AMPK, PPARα and NF-κB were detected by TUNEL, ELISA, and Western blotting, respectively.

Results: Compared to group C, the apoptosis rate was markedly increased, the adiponectin level was decreased, the expression of APPL1, p-AMPK and PPARα was down-regulated and that of NF-κB was up-regulated in group D (P<0.05); in group DE, the apoptosis rate was significantly decreased, the expression of APPL1, p-AMPK and PPARα was up-regulated and that of NF-κB was down-regulated, as compared with group D (P<0.05). The apoptosis rate in group OE was lower than that in group DE, the expression of APPL1, p-AMPK and PPARα was up-regulated and that of NF-κB was down-regulated (P<0.05). In group KD, the adiponectin level was elevated and the cardiomyocyte apoptosis rate was increased, as compared to group D (P<0.05). Furthermore, the expression of APPL1, p-AMPK and PPARα was down-regulated and that of NF-κB was up-regulated compared with group DE (P<0.05).

Conclusions: Exenatide can activate the "APPL1-AMPK-PPARα" anti-apoptosis signaling axis by promoting adiponectin expression in cardiomyocytes and reducing the apoptosis of diabetic cardiomyocytes, thus protecting cardiomyocytes.

Keywords: APPL1; Exenatide; adiponectin; apoptosis; cardiomyocyte.