Recombinant human glucagon-like peptide-1 protects against chronic intermittent hypoxia by improving myocardial energy metabolism and mitochondrial biogenesis
Authors: Lichan Tao
Long Wang
Xiaohong Jiang
Fei Hua
Xiaoyu Yang
Journal: Molecular and Cellular Endocrinology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Chronic intermittent hypoxia; Energy metabolism; Mitochondrial biogenesis; Recombinant human glucagon-like peptide-1.
Affiliations: Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou City, 213003, China., Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou City, 213003, China., Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou City, 213003, China. Electronic address: .

Abstract:  Background and aims: Obstructive sleep apnea syndrome is a chronic disease associated with intermittent hypoxia (IH) and is an important risk factor for cardiovascular disease. Glucagon-like peptide (GLP-1) is a naturally occurring incretin used as a promising therapeutic agent in the treatment of acute myocardial infarction, dilated cardiomyopathy, and advanced heart failure. However, whether GLP-1 can protect against IH-induced cardiac injury is still unclear. Accordingly, in this study, we evaluated the effects of recombinant human GLP-1 (rhGLP-1) on cardiac health in mice. Methods: Mice were subjected to repetitive 5% O2 for 30 s and 21% O2 for 30 s, for a total of 8 h/day for 4 weeks. Subsequently, mice received subcutaneous injection of saline or rhGLP-1 (100 μg/kg, three times per day). Cardiac function, myocardial apoptosis and fibrosis, energy metabolism, and mitochondrial biogenesis were examined for evaluation of cardiac injury. Results: A reduction in diastolic function (E/A ratio) in mice exposed to IH was significantly reversed by rhGLP-1. IH induced marked cardiomyocyte apoptosis and myocardial fibrosis. Additionally, IH resulted in a shift from fatty acid to glucose metabolism in the myocardium with downregulation of peroxisome proliferator-activated receptor (PPAR) α and PPARγ. Moreover, IH caused a reduction in mitochondrial DNA (mtDNA) replication and transcription, together with reduced mtDNA content and impaired mitochondrial ultrastructure. These changes were abolished by rhGLP-1 via activation of PGC-1α and Akt signaling. Conclusions: rhGLP-1 protects against IH-induced cardiac injury by improving myocardial energy metabolism and enhancing the early adaptive changes of mitochondrial biogenesis. 

Retracted: No

PubPeer comments:
 Figure 2A was brought to my attention by a reader. Two panels appear to overlap with each other. ![file] , 
 Dear Elisabeth M Bik: We appreciate your valuable comment. By rechecking the original data, the authors regret that the original version of Figure 2A unfortunately contained some incorrect representative images of TUNEL staining for cardiac tissues. We apologize that at the time of figure assembly, we choose representative images by mistake. We have already contacted the editor of MCE and would provide the original data (.mrtx and .dat) of TUNEL staining for the four groups. We are so sorry for the mistake, and we will submit an errata statement. , 
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 ![file] The institution could not perfrom animal studies, so the authors need to provide the ethnical approval from the Third Affiliated Hospital of Soochow University and the purchase record from Nanjing University. ,