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Leptin: a missing piece in the immunometabolism puzzle

Nature Reviews Immunology volume 20, page 3 (2020)Cite this article

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Obesity is characterized by low-grade inflammation, and a growing number of immunologists are devoted to the study of obesity, thus seeding the field of immunometabolism. I entered this field after training in the laboratory that identified the hormone leptin, a key regulator of fat mass. The ground-breaking paper describing the discovery of leptin is a must-read for those new to the field of immunometabolism (Zhang et al., 1994); deservedly, this paper was celebrated in the 2020 Breakthrough Prizes in Life Science.

The ob/ob mouse line, spontaneously generated in the 1950s by the Jackson Laboratories, showed a Mendelian pattern of inheritance of obesity, which suggested a monogenetic mutation controlling fat mass. Consistent with this idea were Coleman’s parabiosis experiments, which indicated that an unknown blood-borne circulating factor normalized the obese phenotype of ob/ob mice (Coleman, 1978). Using positional cloning technology, Jeffrey Friedman and colleagues mapped the ob gene encoding the circulating factor (later named leptin) to chromosome 6 and isolated it by exon trapping, thus identifying the first piece in the puzzle of what regulates whole body fat mass. They also identified adipose tissue as the source of this circulating factor, which informs the brain on the levels of body fat stores via a negative-feedback loop to regulate adipose mass (Halaas et al., 1995).

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References

Original article

  • Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 (1994)

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Related articles

  • Coleman, D. L. Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 14, 141–148 (1978)

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  • Halass, J. L. et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269, 543–546 (1995)

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  1. University of Oxford, Oxford, UK

    Ana I. Domingos

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  1. Ana I. Domingos
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Correspondence to Ana I. Domingos.

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Domingos, A.I. Leptin: a missing piece in the immunometabolism puzzle. Nat Rev Immunol 20, 3 (2020). https://doi.org/10.1038/s41577-019-0251-3

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