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Do not overlook the role of fructose in obesity

Nature Metabolism (2025)Cite this article

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A recent Perspective1 on obesity pathogenesis examined the energy balance model and carbohydrate–insulin model, discussed risk factors for weight gain and also had a goal to “discuss the importance of purported causal factors for weight gain”. However, it overlooked the important role of fructose metabolism in obesity development. There is now a wealth of data that suggests that dietary fructose, or fructose endogenously produced from glucose, may have a role in obesity2. Indeed, there is evidence that fructose metabolism may play into the energy balance model by stimulating food intake and reducing resting energy metabolism by affecting brain and liver regulatory mechanisms3,4,5,6, and that it may also induce hyperinsulinemia and insulin resistance that may account for many of the proposed effects of the carbohydrate–insulin model7,8. These findings suggest that fructose metabolism may provide a unifying pathway linking the carbohydrate–insulin and energy balance models9.

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Authors and Affiliations

  1. Department of Regenerative Medicine, Shiga University, Shiga, Japan

    Takahiko Nakagawa

  2. Department of Medicine, University of Colorado, Aurora, CO, USA

    Richard J. Johnson

Authors
  1. Takahiko Nakagawa
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  2. Richard J. Johnson
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Correspondence to Richard J. Johnson.

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Competing interests

R.J.J. has equity with Colorado Research Partners LLC, which is developing inhibitors of fructose metabolism. T.N. declares no competing interests.

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Nakagawa, T., Johnson, R.J. Do not overlook the role of fructose in obesity. Nat Metab (2025). https://doi.org/10.1038/s42255-024-01198-2

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