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Metrnl deficiency decreases blood HDL cholesterol and increases blood triglyceride

Abstract

Dyslipidemia is a risk factor for cardiovascular diseases and type 2 diabetes. Several adipokines play important roles in modulation of blood lipids. Metrnl is a recently identified adipokine, and adipose Metrnl participates in regulation of blood triglyceride (TG). In this study, we generated Metrnl global, intestine-specific and liver-specific knockout mice, and explored the effects of Metrnl on serum lipid parameters. Global knockout of Metrnl had no effects on serum lipid parameters under normal chow diet, but increased blood TG by 14%, and decreased total cholesterol (TC) by 16% and high density lipoprotein cholesterol (HDL-C) by 24% under high fat diet. Nevertheless, intestine-specific knockout of Metrnl did not alter the serum lipids parameters under normal chow diet or high fat diet. Notably, liver-specific knockout of Metrnl decreased HDL-C by 24%, TC by 20% and low density lipoprotein cholesterol (LDL-C) by 16% without alterations of blood TG and nonesterified fatty acids (NEFA) under high fat diet. But deficiency of Metrnl in liver did not change VLDL secretion and expression of lipid synthetic and metabolic genes. We conclude that tissue-specific Metrnl controls different components of blood lipids. In addition to modulation of blood TG by adipose Metrnl, blood HDL-C is regulated by liver Metrnl.

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Acknowledgements

This work was supported by grants from the Shanghai Project (16JC1405100), the National Natural Science Foundation of China (81730098 and 81130061) and Medical Innovation Project (16QNP087). This work was also supported by the Open Project Program of the CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences.

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Authors

Contributions

Study conception and design: CYM, ZYL; acquisition of data: QQ, WJH, Si-li Zheng, Sai-long Zhang; analysis and interpretation of data: YYL, ZYL, CYM; drafting of manuscript: ZYL, QQ; critical revision: CYM.

Corresponding authors

Correspondence to Zhi-yong Li or Chao-yu Miao.

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The authors declare no competing interests.

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Cite this article

Qi, Q., Hu, Wj., Zheng, Sl. et al. Metrnl deficiency decreases blood HDL cholesterol and increases blood triglyceride. Acta Pharmacol Sin 41, 1568–1575 (2020). https://doi.org/10.1038/s41401-020-0368-8

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Keywords

  • Metrnl
  • dyslipidemia
  • serum lipid parameters
  • HDL cholesterol
  • triglyceride
  • Metrnl tissue-specific knockout mice

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