Effects of Acute Cold Stress on Liver O-GlcNAcylation and Glycometabolism in Mice.

Ruizhi Yao,Hongzhao Shi,Shuai Lian,Yang Liu,Huanmin Yang,Peng Liu,Shize Li,Yuying Yang

doi:10.3390/ijms19092815

Ruizhi Yao, Hongzhao Shi + Show 6 more

Open Access

https://doi.org/10.3390/ijms19092815

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Abstract

Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) regulates many biological processes. Studies have shown that O-GlcNAc modification levels can increase during acute stress and suggested that this may contribute to the survival of the cell. This study investigated the possible effects of O-GlcNAcylation that regulate glucose metabolism, apoptosis, and autophagy in the liver after acute cold stress. Male C57BL/6 mice were exposed to cold conditions (4 °C) for 0, 2, 4, and 6 h, then their livers were extracted and the expression of proteins involved in glucose metabolism, apoptosis, and autophagy was determined. It was found that acute cold stress increased global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels. This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β). The levels of glycolytic intermediates, fructose-1,6-diphosphate (FDP) and pyruvic acid (PA), were found to show a brief increase followed by a sharp decrease. Additionally, adenosine triphosphate (ATP), as the main cellular energy source, had a sharp increase. Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress. Therefore, acute cold stress was found to increase O-GlcNAc modification levels, which may have resulted in the decrease of the essential processes of apoptosis and autophagy, promoting cell survival, while altering glycose transport, glycogen synthesis, and glycolysis in the liver.

Highlights

Stress is known to affect multiple biochemical regulatory systems, and is considered to be a major risk factor for a number of different diseases [1]
Studies have shown that glycosylation of proteins with O-GlcNAc is involved in the regulation of energy metabolism, autophagy, and apoptosis [21,26,27]
To test changes in glucose, insulin, and glucagon under acute cold stress in plasma, the authors of this study examined and compared the response of both the control and stressed groups

Summary

Introduction

Stress is known to affect multiple biochemical regulatory systems, and is considered to be a major risk factor for a number of different diseases [1]. Studies have shown that glycosylation of proteins with O-GlcNAc is involved in the regulation of energy metabolism, autophagy, and apoptosis [21,26,27]. Additional research on the effects of O-GlcNAc modification under acute cold stress on hepatic metabolism and autophagy in mice is limited.

Results

Conclusion