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Blunted Cardiac AMPK Response is Associated with Susceptibility to Ischemia/Reperfusion in Male Offspring of Gestational Diabetic Rats.
journal contributionposted on 2019-06-18, 15:38 authored by X Luo, H Zou, P Xu, L Wen, JL Stanley, X Jiang, T-L Han, D Olson, C Peng, C Zhang, X Xiao, C Tong, H Qi, PN Baker
BACKGROUND/AIMS: Gestational diabetes mellitus (GDM) is closely associated with early perinatal complications and long-term health problems, such as cardiovascular disease, in offspring. AMP-activated protein kinase (AMPK) is cardioprotective, particularly in the treatment of ischemia/reperfusion (I/R). However, whether GDM programs offspring susceptibility to cardiac I/R and the involvement of AMPK remain unclear. METHODS: Streptozotocin was administered to rats during mid pregnancy; the postpartum maternal metabolome was assessed by chromatography-mass spectrometry (GC-MS). Male offspring were subjected to body composition scanning followed by ex vivo global I/R. Cardiac signaling was determined by Western blotting. RESULTS: The body weights (BWs) of the GDM male offspring were significantly heavier than those of the control group from the age of 8 weeks; the heart weights (HWs) and HW/BW were also increased in the GDM group compared to the control group. The ex vivo post-I/R cardiac contractile function recovery was significantly compromised in the GDM male offspring. The phosphorylation of AMPK and ACC was elevated by ex vivo I/R in both groups, but to a significantly lesser extent in the GDM group. CONCLUSION: GDM male offspring rats have higher risks of overgrowth and intolerance to cardiac I/R, which may be due to a compromised AMPK signaling pathway.
This work was supported by grants from the National Natural Science Foundation of China (No. 81520108013, 81771613, 81671488, and 81471472), Chongqing Education Committee (CXTDX201601014 and KJ1500223), Chongqing Medical University (CYYQ201507), Commission of Science and Technology of Chongqing Municipality (cstc2017jcyjBX0045), and Chongqing Entrepreneurship and Innovation Supporting Program for Returned Overseas Students (cx2017104). We would also like to acknowledge support from the “111 program” of the Ministry of Education P.R.C. and the State Administration of Foreign Experts Affairs P.R.C.
CitationCellular Physiology and Biochemistry, 2019, 52 (5), pp. 1103-1116
Author affiliation/Organisation/COLLEGE OF LIFE SCIENCES
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