Fat and Energy Partitioning: Longitudinal Observations in Leptin-treated Adults Homozygous for a Lep Mutation


  • The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Clinical Research, Metabolism, RY34A, Merck Research Laboratories, 126 E. Lincoln Avenue, PO Box 2000, Rahway, NJ 07065-0900. E-mail: Steven_Heymsfield@Merck.Com


Objective: Partitioning of body energy content in the aleptinemic ob/ob mouse differs from that in wild-type mice, but it is not known whether parallel differences exist between humans with leptin (Lep) gene mutations and healthy adults. The objective of this study was to evaluate body composition in three leptin-treated Turkish adults homozygous for a missense mutation (C→T substitution at codon 105 resulting in Arg→Trp) of Lep.

Research Methods and Procedures: Subjects, one male and two female Turkish family members, were evaluated at baseline and treated for 18 months with r-MetHuLeptin. Patient data (fat mass, energy content) were compared with adult sex-specific predicted values (adjusted for weight, height, and age) derived in healthy control subjects.

Results: Weight loss with leptin treatment was substantial, ranging from 43.9% to 52.1%. At baseline and with leptin treatment, the two women had a fat mass and energy content similar (±12%) to predicted values. Baseline fat and energy content in the male patient was high compared with predicted values (e.g., fat +33%) but approached and reached normal values (e.g., fat, +2%) after 18 months of leptin therapy.

Discussion: Adult women with Lep mutations had body composition similar to normal women at baseline and with leptin treatment. In contrast, the man with a Lep mutation had high body fat in the untreated state but a normal male phenotype with leptin administration, possibly secondary to androgenic fat partitioning effects. Fat and energy partitioning can, thus, be quantitatively assessed and linked with potential hormonal mechanisms in humans with inherited disturbances in energy regulation.