, Volume 45, Issue 3, pp 401–408 | Cite as

Changes in levels of peripheral hormones controlling appetite are inconsistent with hyperphagia in leptin-deficient subjects

  • Sadia Saeed
  • Paul R. Bech
  • Tayyaba Hafeez
  • Rabail Alam
  • Mario Falchi
  • Mohammad A. Ghatei
  • Stephen R. Bloom
  • Muhammad Arslan
  • Philippe Froguel
Original Article


Congenital leptin deficiency, a rare genetic disorder due to a homozygous mutation in the leptin gene (LEP), is accompanied by extreme obesity and hyperphagia. A number of gastrointestinal hormones have been shown to critically regulate food intake but their physiological role in hyperphagic response in congenital leptin deficiency has not been elucidated. This study is the first to evaluate the fasting and postprandial profiles of gut-derived hormones in homozygous and heterozygous carriers of LEP mutation. The study subjects from two consanguineous families consisted of five homozygous and eight heterozygous carriers of LEP mutation, c.398delG. Ten wild-type normal-weight subjects served as controls. Fasting and 1-h postprandial plasma ghrelin, glucagon-like peptide (GLP) 1, peptide YY (PYY), leptin and insulin levels were measured by immunoassays. Fasting plasma ghrelin levels in homozygotes remained remarkably unchanged following food consumption (P = 0.33) in contrast to a significant decline in heterozygous (P < 0.03) and normal (P < 0.02) subjects. A significant postprandial increase in PYY was observed in heterozygous (P < 0.02) and control subjects (P < 0.01), but not in the homozygous group (P = 0.22). A postprandial rise in GLP-1 levels was significant (P < 0.02) in all groups. Interestingly, fasting leptin levels in heterozygotes were not significantly different from controls and did not change significantly following meal. Our results demonstrate that gut hormones play little or no physiological role in driving the hyperphagic response of leptin-deficient subjects. In contrast, fasting and postprandial levels of gut hormones in heterozygous mutation carriers were comparable to those of normal-weight controls.


Leptin deficiency Ghrelin PYY GLP-1 Insulin 



This study was supported by Imperial NIHR Biomedical Research Centre Grant (WPGA_P33399; P. F). Support of Dr Alex Blakemore during initial stages of this study and expert technical help of Mohsin Arshad is gratefully acknowledged. We thank the participating family members for their cooperation.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Sadia Saeed
    • 1
  • Paul R. Bech
    • 2
  • Tayyaba Hafeez
    • 3
  • Rabail Alam
    • 4
  • Mario Falchi
    • 1
  • Mohammad A. Ghatei
    • 2
  • Stephen R. Bloom
    • 2
  • Muhammad Arslan
    • 4
    • 5
  • Philippe Froguel
    • 1
    • 6
  1. 1.Department of Genomics of Common DiseaseHammersmith Hospital, Imperial College LondonLondonUK
  2. 2.Department of MedicineHammersmith Hospital, Imperial College LondonLondonUK
  3. 3.Medical Special Unit, Division of MedicineServices HospitalLahorePakistan
  4. 4.Centre for Research in Molecular MedicineUniversity of LahoreLahorePakistan
  5. 5.Department of Biological SciencesForman Christian College (A Chartered University)LahorePakistan
  6. 6.Centre National de la Recherche ScientifiqueUniversity Lille North of France, Pasteur InstituteLilleFrance

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