Abstract

The extreme obesity of the obese (ob/ob) mouse is attributable to mutations in the gene encoding leptin, an adipocyte-specific secreted protein which has profound effects on appetite and energy expenditure. We know of no equivalent evidence regarding leptin's role in the control of fat mass in humans. We have examined two severely obese children who are members of the same highly consanguineous pedigree. Their serum leptin levels were very low despite their markedly elevated fat mass and, in both, a homozygous frame-shift mutation involving the deletion of a single guanine nucleotide in codon 133 of the gene for leptin was found. The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans.

Keywords

LeptinEndocrinologyInternal medicineObesityAppetiteMutationAdipocyteEnergy expenditureRegulatorGeneMedicineFat massBiologyGeneticsAdipose tissue

MeSH Terms

AdultAge of OnsetAnimalsBody CompositionCHO CellsChildChildPreschoolConsanguinityCricetinaeFemaleFrameshift MutationHomozygoteHumansLeptinMaleMetabolismInborn ErrorsMiceMiceObeseMolecular Sequence DataObesityPedigreePolymorphismSingle-Stranded ConformationalProteinsSequence AnalysisDNATransfection

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Publication Info

Year
1997
Type
article
Volume
387
Issue
6636
Pages
903-908
Citations
2915
Access
Closed

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Cite This

Carl Montague, I. Sadaf Farooqi, Jonathan P. Whitehead et al. (1997). Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature , 387 (6636) , 903-908. https://doi.org/10.1038/43185

Identifiers

DOI
10.1038/43185
PMID
9202122

Data Quality

Data completeness: 86%