Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Metrnl deficiency decreases blood HDL cholesterol and increases blood triglyceride


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7


  1. 1.

    Genest J, McPherson R, Frohlich J, Anderson T, Campbell N, Carpentier A, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult - 2009 recommendations. Can J Cardiol. 2009;25:567–79.

    CAS  Article  Google Scholar 

  2. 2.

    Goldberg IJ. Clinical review 124: Diabetic dyslipidemia: causes and consequences. J Clin Endocrinol Metab. 2001;86:965–71.

    CAS  Article  Google Scholar 

  3. 3.

    Reitz C. Dyslipidemia and dementia: current epidemiology, genetic evidence, and mechanisms behind the associations. J Alzheimers Dis 2012;30(Suppl 2):S127–45.

    Article  Google Scholar 

  4. 4.

    Chen Z, Zhao GH, Zhang YK, Shen GS, Xu YJ, Xu NW. Research on the correlation of diabetes mellitus complicated with osteoporosis with lipid metabolism, adipokines and inflammatory factors and its regression analysis. Eur Rev Med Pharmacol Sci. 2017;21:3900–5.

    CAS  PubMed  Google Scholar 

  5. 5.

    Rahimlou M, Mirzaei K, Keshavarz SA, Hossein-Nezhad A. Association of circulating adipokines with metabolic dyslipidemia in obese versus non-obese individuals. Diabetes Metab Syndr. 2016;10:S60–5.

    Article  Google Scholar 

  6. 6.

    Coimbra S, Reis F. The protective role of adiponectin for lipoproteins in end-stage renal disease patients: relationship with diabetes and body mass index. Oxid Med Cell Longev. 2019;2019:3021785.

    Article  Google Scholar 

  7. 7.

    Katsiki N, Mikhailidis DP, Banach M. Leptin, cardiovascular diseases and type 2 diabetes mellitus. Acta Pharmacol Sin. 2018;39:1176–88.

    CAS  Article  Google Scholar 

  8. 8.

    Habib SS, Eshki A, AlTassan B, Fatani D, Helmi H, AlSaif S. Relationship of serum novel adipokine chemerin levels with body composition, insulin resistance, dyslipidemia and diabesity in Saudi women. Eur Rev Med Pharmacol Sci. 2017;21:1296–302.

    CAS  PubMed  Google Scholar 

  9. 9.

    Korolczuk A, Beltowski J. Progranulin, a new adipokine at the crossroads of metabolic syndrome, diabetes, dyslipidemia and hypertension. Curr Pharm Des. 2017;23:1533–9.

    CAS  Article  Google Scholar 

  10. 10.

    Li ZY, Zheng SL, Wang P, Xu TY, Guan YF, Zhang YJ, et al. Subfatin is a novel adipokine and unlike Meteorin in adipose and brain expression. CNS Neurosci Ther. 2014;20:344–54.

    CAS  Article  Google Scholar 

  11. 11.

    Jorgensen JR, Fransson A, Fjord-Larsen L, Thompson LH, Houchins JP, Andrade N, et al. Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo. Exp Neurol 2012;233:172–81.

    CAS  Article  Google Scholar 

  12. 12.

    Rao RR, Long JZ, White JP, Svensson KJ, Lou J, Lokurkar I, et al. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell 2014;157:1279–91.

    CAS  Article  Google Scholar 

  13. 13.

    Ushach I, Arrevillaga-Boni G, Heller GN, Pone E, Hernandez-Ruiz M, Catalan-Dibene J, et al. Meteorin-like/meteorin-beta is a novel immunoregulatory cytokine associated with inflammation. J Immunol 2018;201:3669–76.

    CAS  Article  Google Scholar 

  14. 14.

    Zheng SL, Li ZY, Song J, Liu JM, Miao CY. Metrnl: a secreted protein with new emerging functions. Acta Pharmacol Sin. 2016;37:571–9.

    CAS  Article  Google Scholar 

  15. 15.

    Li ZY, Song J, Zheng SL, Fan MB, Guan YF, Qu Y, et al. Adipocyte metrnl antagonizes insulin resistance through PPARgamma signaling. Diabetes 2015;64:4011–22.

    CAS  Article  Google Scholar 

  16. 16.

    Dooley TP, Miranda M, Jones NC, DePamphilis ML. Transactivation of the adenovirus EIIa promoter in the absence of adenovirus E1A protein is restricted to mouse oocytes and preimplantation embryos. Development. 1989;107:945–56.

    CAS  PubMed  Google Scholar 

  17. 17.

    Li ZY, Fan MB, Zhang SL, Qu Y, Zheng SL, Song J, et al. Intestinal Metrnl released into the gut lumen acts as a local regulator for gut antimicrobial peptides. Acta Pharmacol Sin. 2016;37:1458–66.

    Article  Google Scholar 

  18. 18.

    Wan JF, Chu SF, Zhou X, Li YT, He WB, Tan F, et al. Ursodeoxycholic acid protects interstitial Cajal-like cells in the gallbladder from undergoing apoptosis by inhibiting TNF-alpha expression. Acta Pharmacol Sin. 2018;39:1493–500.

    CAS  Article  Google Scholar 

  19. 19.

    Zheng SL, Li ZY, Zhang Z, Wang DS, Xu J, Miao CY. Evaluation of two commercial enzyme-linked immunosorbent assay kits for the detection of human circulating metrnl. Chem Pharm Bull. 2018;66:391–8.

    CAS  Article  Google Scholar 

  20. 20.

    Ge MX, Niu WX, Ren JF, Cai SY, Yu DK, Liu HT, et al. A novel ASBT inhibitor, IMB17-15, repressed nonalcoholic fatty liver disease development in high-fat diet-fed Syrian golden hamsters. Acta Pharmacol Sin. 2019;40:895–907.

    CAS  Article  Google Scholar 

  21. 21.

    Wang X, Xu TY, Liu XZ, Zhang SL, Wang P, Li ZY, et al. Discovery of novel inhibitors and fluorescent probe targeting NAMPT. Sci Rep. 2015;5:12657.

    CAS  Article  Google Scholar 

  22. 22.

    Mobin MB, Gerstberger S, Teupser D, Campana B, Charisse K, Heim MH, et al. The RNA-binding protein vigilin regulates VLDL secretion through modulation of Apob mRNA translation. Nat Commun 2016;7:12848.

    CAS  Article  Google Scholar 

  23. 23.

    Hussain MM. Intestinal lipid absorption and lipoprotein formation. Curr Opin Lipido. 2014;25:200–6.

    CAS  Article  Google Scholar 

  24. 24.

    Curb JD, Abbott RD, Rodriguez BL, Masaki K, Chen R, Sharp DS, et al. A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly. J Lipid Res. 2004;45:948–53.

    CAS  Article  Google Scholar 

  25. 25.

    Brown MS, Goldstein JL. How LDL receptors influence cholesterol and atherosclerosis. Sci Am 1984;251:58–66.

    CAS  Article  Google Scholar 

Download references


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.

Author information




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.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

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).

Download citation


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

Further reading


Quick links