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Metabolism

Partial leptin deficiency and human adiposity

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Abstract

The adipocyte-derived hormone leptin is crucial for energy homeostasis in mammals; mice1 and humans2,3 without it suffer from a voracious appetite and extreme obesity. The effect on energy balance of variations in plasma leptin above a minimal threshold is uncertain, however, particularly in humans. Here we examine a group of individuals who are genetically partially deficient in leptin, and show that differences in circulating leptin levels within the range found in normal human populations can directly influence the laying down of fat tissue (adiposity).

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Figure 1: Human heterozygotes for the ΔG133 mutation in the leptin gene have low serum leptin levels and increased body-fat percentage relative to controls.

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Authors and Affiliations

  1. University Departments of Medicine and Clinical Biochemistry, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK

    I. Sadaf Farooqi, Julia M. Keogh & Stephen O'Rahilly

  2. University Department of Medicine, City Hospital, Dudley Road, Birmingham, B18 7QH, UK

    Sri Kamath & Gregory Y. H. Lip

  3. MRC Human Nutrition Research, Fulbourn Road, Cambridge, CB1 9NL, UK

    Sarah Jones & Susan A. Jebb

  4. Department of Medical Genetics, Alberta Children's Hospital, 18200 Richmond Road Southwest, Alberta, T2T 5C7, Calgary, Canada

    William T. Gibson

  5. Department of Paediatric Endocrinology, Alberta Children's Hospital, 18200 Richmond Road Southwest, Alberta, T2T 5C7, Calgary, Canada

    Rebecca Trussell

Authors
  1. I. Sadaf Farooqi
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  2. Julia M. Keogh
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  3. Sri Kamath
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  4. Sarah Jones
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  5. William T. Gibson
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  6. Rebecca Trussell
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  7. Susan A. Jebb
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  8. Gregory Y. H. Lip
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  9. Stephen O'Rahilly
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Corresponding author

Correspondence to Stephen O'Rahilly.

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Farooqi, I., Keogh, J., Kamath, S. et al. Partial leptin deficiency and human adiposity. Nature 414, 34–35 (2001). https://doi.org/10.1038/35102112

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