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Metformin-induced hepatokine reduces appetite

Nature Reviews Endocrinology volume 16, page 131 (2020)Cite this article

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Metformin is commonly prescribed to manage type 2 diabetes mellitus (T2DM), as it decreases plasma concentrations of glucose by inhibiting hepatic glucose production. The drug also has other effects via unclear mechanisms, for example, reducing appetite in humans and other animals, and decreasing the effects of a number of chronic diseases of ageing in animal models. A study in Nature Metabolism now demonstrates that a metformin-induced hepatokine (GDF15) mediates the effects of the drug on appetite.

The researchers treated primary hepatocytes from wild-type mice with metformin and used transcriptomic analyses to identify differentially expressed transcripts. The identified genes were then cross referenced with the known mouse secretome, giving rise to a list of 51 secreted gene products affected by metformin, including upregulation of GDF15. Next, 900 serum proteins from 16 metformin-naive patients with T2DM who were randomized to receive metformin or no metformin (from the REMIT trial) were analysed. Interestingly, metformin treatment significantly upregulated the levels of GDF15, corresponding with the mouse data. In addition, in vitro studies of primary mouse hepatocytes showed that the mechanism of metformin-induced GDF15 secretion involved the integrated stress pathway.

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References

Original article

  • Day, E. A. et al. Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss. Nat. Metab. 1, 1202–1208 (2019)

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  1. Nature Reviews Endocrinology http://www.nature.com/nrendo/

    Shimona Starling

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  1. Shimona Starling
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Correspondence to Shimona Starling.

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Starling, S. Metformin-induced hepatokine reduces appetite. Nat Rev Endocrinol 16, 131 (2020). https://doi.org/10.1038/s41574-019-0315-2

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