Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency.
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.
Farooqi
I Sadaf
IS
University Department of Medicine, Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, United Kingdom. afarooqi@hgmp.mrc.ac.uk
Matarese
Giuseppe
G
Lord
Graham M
GM
Keogh
Julia M
JM
Lawrence
Elizabeth
E
Agwu
Chizo
C
Sanna
Veronica
V
Jebb
Susan A
SA
Perna
Francesco
F
Fontana
Silvia
S
Lechler
Robert I
RI
DePaoli
Alex M
AM
O'Rahilly
Stephen
S
D000818:Animals; D002648:Child; D002675:Child, Preschool; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006801:Humans; D020738:Leptin / Q000172:deficiency* / Q000235:genetics / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D009490:Neurosecretory Systems / Q000187:drug effects / Q000503:physiopathology; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D015431:Weight Loss / Q000187:drug effects
D020738:Leptin; D011994:Recombinant Proteins