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.

  • News & Views
  • Published:


A stochastic basis for metabolic phenotypes

It has long been recognized that some phenotypic variation in mammals cannot be explained by known genetic or environmental variables. Here, the authors show that the absence of Nnat expression is associated with polyphenism in mice with the same genotype. Broadly consistent effects are also found in humans.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: A mouse model for understanding the origins of unexplained phenotypic variation.


  1. Gärtner, K. Lab. Anim. 24, 71–77 (1990).

    Article  Google Scholar 

  2. Rakyan, V. K., Blewitt, M. E., Druker, R., Preis, J. I. & Whitelaw, E. Trends Genet. 18, 348–351 (2002).

    Article  CAS  Google Scholar 

  3. Panzeri, I. & Pospisilik, J. A. Mol. Metab. 14, 26–38 (2018).

    Article  CAS  Google Scholar 

  4. Yang, C. H. et al. Nat. Metab. (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Dalgaard, K. et al. Cell 164, 353–364 (2016).

    Article  CAS  Google Scholar 

  6. Whitelaw, N. C. et al. Genome Biol. 11, R111 (2010).

    Article  CAS  Google Scholar 

  7. Millership, S. J. et al. Mol. Metab. 18, 97–106 (2018).

    Article  CAS  Google Scholar 

  8. Vrang, N. et al. Obesity (Silver Spring) 18, 1289–1296 (2010).

    Article  Google Scholar 

  9. Li, X., Thomason, P. A., Withers, D. J. & Scott, J. BMC Syst. Biol. 4, 175 (2010).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Michelle L. Holland or Vardhman K. Rakyan.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Holland, M.L., Rakyan, V.K. A stochastic basis for metabolic phenotypes. Nat Metab 4, 1091–1092 (2022).

Download citation

  • Published:

  • Issue Date:

  • DOI:


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing