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Metabolism

The kidney is a novel target of metformin

Nature Reviews Nephrology volume 19, page 424 (2023)Cite this article

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Zhang and colleagues found that infusion of metformin compared with saline reduced food intake and weight gain upon refeeding in male rats fed a high-fat diet (HFD). In addition, metformin increased the plasma levels of growth/differentiation factor 15 (GDF15) and upregulated kidney GDF15 expression in these rats. Kidney-specific knockdown of GDF15 in HFD-fed rats significantly reduced the metformin-induced increase in plasma GDF15 levels as well as the food intake-lowering and weight gain-reducing effects of metformin compared with saline.

The researchers also showed that knockdown of the GDF15 receptor GDNF family receptor α-like (GFRAL) in the area postrema of the brain abrogated the ability of metformin to reduce food intake and refeeding-induced weight gain in HFD rats. They conclude that metformin induces GDF15 synthesis in the kidney, resulting in an increase in plasma GDF15 levels and activation of GFRAL in the area postrema. This GDF15-dependent kidney–area postrema axis mediates the effects of metformin on food intake and weight gain in male rats. Further research is required to investigate the clinical relevance of changes in kidney GDF15 expression following metformin treatment in humans.

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Original article

  • Zhang, S.-Y. et al. Metformin triggers a kidney GDF15-dependent area postrema axis to regulate food intake and body weight. Cell Metab. 35, 875–886 (2023)

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  1. Nature Reviews Nephrology http://www.nature.com/nrneph

    Ellen F. Carney

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  1. Ellen F. Carney
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Correspondence to Ellen F. Carney.

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Carney, E.F. The kidney is a novel target of metformin. Nat Rev Nephrol 19, 424 (2023). https://doi.org/10.1038/s41581-023-00728-7

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  • DOI: https://doi.org/10.1038/s41581-023-00728-7

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