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Selenoprotein F knockout leads to glucose and lipid metabolism disorders in mice

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Abstract

Selenoprotein F (Selenof), an endoplasmic reticulum (ER)-resident protein, is considered to be involved in glycoprotein folding and quality control in the ER. However, its function has not yet been thoroughly addressed. In this study, proteomics analysis revealed that Selenof deficiency in mice led to the differential expression of hepatic proteins associated with glucose and lipid metabolism. The phenotype analysis revealed that Selenof knockout mice showed glucose intolerance and insulin reduction, even with a normal diet. Additionally, Selenof knockout exacerbated high-fat diet-induced obesity, hyperglycemia, glucose intolerance, and hepatic steatosis. Furthermore, lipoprotein lipase and carboxylesterase 1D, two glycoproteins involved in lipid metabolism, were significantly decreased in the liver of Selenof knockout mice with a normal or high-fat diet. Collectively, these findings suggested that Selenof deficiency might cause the perturbation of glycoprotein quality control and thus contribute to glucose and lipid metabolism disorders, implying a novel biological function of Selenof.

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Abbreviations

Apoc3:

Apolipoprotein C-III

BSA:

Bovine serum albumin

Ces1D:

Carboxylesterase 1D

DAB:

Diaminobenzidine

DEPs:

Differentially expressed proteins

ER:

Endoplasmic reticulum

eWAT:

Epididymal white adipose tissue

FFAs:

Free fatty acids

GSIS:

Glucose stimulated insulin secretion

GTT:

Glucose tolerance test

HE:

Hematoxylin and eosin

HFD:

High-fat diet

IHC:

Immunohistochemistry

iTRAQ:

Isobaric tags for relative and absolute quantification

ITT:

Insulin tolerance test

KEGG:

Kyoto encyclopedia of genes and genomes

KO:

Knockout

LDL-C:

Low-density lipoprotein cholesterol

Lpl:

Lipoprotein lipase

PET:

Positron emission tomography

TC:

Total cholesterol

TG:

Triglycerides

PPARs:

Peroxisome proliferator-activated receptors

UGGT:

UDP-glucose:glycoprotein glucosyltransferase

VLDL:

Very low-density lipoproteins

WT:

Wildtype

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Acknowledgements

This study was financially supported by grants from the National Natural Science Foundation of China (Project Nos. 21271077, 31972920, 21771068, and 81372984). Thanks to Academician Kui Wang of Peking University and Prof. Huibi Xu of Huazhong University of Science and Technology for their support and care in our research and guidance in preparing this manuscript. Thanks to the faculties of Analytical and Testing Center of Huazhong University of Science and Technology for their help in the bioanalysis.

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Authors and Affiliations

  1. Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China

    Xiaoxiang Zheng, Xiaoming Li, Hongmei Liu, Jun Zhou & Kaixun Huang

  2. College of Life Sciences and Oceanography, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, 518060, Guangdong, China

    Bingyu Ren & Jing Tian

  3. College of Life Science, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China

    Huanhuan Yan & Qingguo Xie

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  1. Xiaoxiang Zheng
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  2. Bingyu Ren
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  3. Xiaoming Li
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  4. Huanhuan Yan
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  7. Jun Zhou
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  9. Kaixun Huang
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Contributions

XXZ, KXH, JZ and JT conceived and designed the work; designed the experiments; XXZ, BYR, XML and JZ performed the experiments or partial experiments; HHY and QGX performed the PET experiments; XXZ, BYR analyzed the data; XXZ, HML, JT, JZ and KXH wrote the manuscript.

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Correspondence to Jun Zhou, Jing Tian or Kaixun Huang.

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Zheng, X., Ren, B., Li, X. et al. Selenoprotein F knockout leads to glucose and lipid metabolism disorders in mice. J Biol Inorg Chem 25, 1009–1022 (2020). https://doi.org/10.1007/s00775-020-01821-z

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