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The metabolic changes in the hippocampus of an atherosclerotic rat model and the regulation of aerobic training

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Abstract

Atherosclerosis has been associated with the progression of cognitive impairment and the effect of metabolic changes in the brain on cognitive function may be pronounced. The aim is to reveal the metabolic changes during atherosclerosis and clarify the possible role of exercise in regulating hippocampal metabolism. Hence, A rat model of atherosclerosis was established by high-fat diet feeding in combination with vitamin D3 intraperitoneal injection, then 4 weeks of aerobic exercise was conducted. Metabolomics based on GC-MS was applied to detect small molecules metabolites and western blot was used to detect the concentration of enzymes involved in metabolic changes in rat hippocampus. Compared to the control group, metabolites including xylulose 5-phosphate, threonine, succinate, and nonanoic acid were markedly elevated, whereas methyl arachidonic acid and methyl stearate decreased in the AS group, accompanied by a raised concentration of aldose reductase and glucose 6-phosphate dehydrogenase as well as a declined concentration of acetyl-CoA carboxylase and fatty acid synthase. After 4 weeks’ aerobic exercise, the levels of succinic acid, branched chain amino acids, nonanoic acid, desmosterol, and aldose reductase decreased, whereas methyl arachidonic acid, methyl stearate, and glyceraldehyde-3-phosphate elevated in the hippocampus of the TAS group in comparison with the AS group. These results suggest that atherosclerosis could cause a severe metabolic disturbance, and aerobic exercise plays an important role in regulating atherosclerosis-induced disorder of glucose metabolism in the hippocampus.

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Abbreviations

HDL:

high-density lipoprotein cholesterol

PUFAs:

polyunsaturated fatty acids

FATP-1:

fatty acid transporter-1

GLUT-1:

glucose transporter-1

SDHA:

succinate dehydrogenase subunit A

G-6-PD:

glucose 6-phosphatedehydrogenase

AR:

aldose reductase

FASN:

fatty acid synthase

p-ACC:

phospho-Acetyl-CoA Carboxylase

ACC:

Acetyl-CoA Carboxylase

G-6-P:

glucose 6-phosphate

F-1,6-BP:

fructose 1,6-diphosphate

Xyl-5-P:

xylulose 5-phosphate

Rib-5-P:

ribose 5-phosphate

3-GP:

glyceraldehyde-3-phosphate

G-3-P:

glycerate 3-phosphate

α-keto:

alpha-ketoglutarate

FAME:

fatty acid methyl ester

AA:

arachidonic acid

NA:

nonanoic acid

PPP:

Pentose Phosphate Pathway

BCAA:

branched-chain amino acids;

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Acknowledgements

We thank Qian Wang, Mingming Li, Xiao-huan Chen and lin lu for providing support to achieve this work. Thanks for the support from National Natural Science Foundation of China (81572241) and Shanghai Key Lab of Human Performance(Shanghai University of sport)(NO. 11DZ2261100).

Funding

This work was supported by the grant of National Natural Science Foundation of China (81572241) and Shanghai Key Lab of Human Performance(Shanghai University of sport)(NO. 11DZ2261100).

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Authors and Affiliations

  1. Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, 200438, China

    Beibei Liu, Xiaojing Lin, Jingyun Hu & Shujie Lou

  2. Department of Rehabilitation Medicine, Weifang Medical University, Weifang, 261053, China

    Beibei Liu

  3. Post-doctoral station of clinical medicine, Tongji Hospital, medical school of Tongji University, Shanghai, 200092, China

    Jingjing Li

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  1. Beibei Liu
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Beibei Liu and Jingjing Li. The first draft of the manuscript was written by Beibei Liu and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Shujie Lou.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the Institutional Animal Care and Use Committees of the Shanghai University of Sport at which the studies were conducted.

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Highlights

• Glucose and lipid metabolism disrupted in hippocampus of atherosclerotic rats.

• Expressions of key enzymes involved in glucose and lipid metabolism changed.

• Aerobic training may improve metabolism in the hippocampus of atherosclerotic rats.

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Liu, B., Li, J., Lin, X. et al. The metabolic changes in the hippocampus of an atherosclerotic rat model and the regulation of aerobic training. Metab Brain Dis 35, 1017–1034 (2020). https://doi.org/10.1007/s11011-020-00566-7

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