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Link to original content: http://pubmed.ncbi.nlm.nih.gov/12393845/
Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency - PubMed Skip to main page content
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Case Reports
. 2002 Oct;110(8):1093-103.
doi: 10.1172/JCI15693.

Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency

I Sadaf Farooqi  1 , Giuseppe Matarese, Graham M Lord, Julia M Keogh, Elizabeth Lawrence, Chizo Agwu, Veronica Sanna, Susan A Jebb, Francesco Perna, Silvia Fontana, Robert I Lechler, Alex M DePaoli, Stephen O'Rahilly
Affiliations
Case Reports

Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency

I Sadaf Farooqi et al. J Clin Invest. 2002 Oct.

Abstract

The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for the existence of multiple physiological functions of this hormone in rodents. In contrast, information regarding the roles of this hormone in humans is limited. Three morbidly obese children, who were congenitally deficient in leptin, were treated with daily subcutaneous injections of recombinant human leptin for up to 4 years with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia. Leptin therapy resulted in a rapid and sustained increase in plasma thyroid hormone levels and, through its age-dependent effects on gonadotropin secretion, facilitated appropriately timed pubertal development. Leptin deficiency was associated with reduced numbers of circulating CD4(+) T cells and impaired T cell proliferation and cytokine release, all of which were reversed by recombinant human leptin administration. The subcutaneous administration of recombinant human leptin has major and sustained beneficial effects on the multiple phenotypic abnormalities associated with congenital human leptin deficiency.

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Figures

Figure 1
Figure 1
Effects of r-metHuLeptin on weight in three children with congenital leptin deficiency. (a) Weights of child A compared with normal centiles for girls and of child B and child C compared with normal centiles for boys. Arrows indicate the start of r-metHuLeptin therapy. (b) Clinical photographs of child B before (height = 107 cm) and 24 months after r-metHuLeptin therapy (height = 124 cm) (reproduced with the permission of the child’s parents).
Figure 2
Figure 2
Effects of r-metHuLeptin therapy on energy intake. (a) Energy intake at an ad libitum test meal before (black bars) and 2 months after (white bars) r-metHuLeptin therapy in child A, B, and C. Energy intake (KJ) expressed per kilogram lean body mass to compare intake of subjects of different age and body size. (b) Changes in body mass index SDS (BMI SDS) (filled symbols) and energy intake at an 18-MJ ad libitum test meal (gray bars) during 36 months of treatment in child B. Panels indicate duration of r-metHuLeptin dose expressed as a percentage of predicted serum leptin concentration based on age, gender, and body composition.
Figure 3
Figure 3
Leptin therapy results in pubertal development at an appropriate developmental age. (a) Pulsatile secretion of LH and FSH in child A after 12 and 24 months of r-metHuLeptin therapy. (b) No pulsatile secretion after 12 months of treatment in child B.
Figure 4
Figure 4
Effect of r-metHuLeptin on T cell proliferation and cytokine production in child C. (a) Proliferative responses of peripheral lymphocytes to T cell–specific stimuli at three different time points before (–) and after (+) recombinant leptin treatment. All data are from triplicate cultures and expressed as mean ± SD. Proliferative responses from normal age-matched controls were measured in parallel experiments (mean shown as single point ± SD). (b) Cytokine profiles in child C at three different time points before (–) and after (+) recombinant leptin treatment. Cytokine measurements from normal age-matched controls were measured in parallel experiments (mean shown as single point ± SEM).
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