Leptin in human physiology and therapeutics.
Leptin regulates energy homeostasis and reproductive, neuroendocrine, immune, and metabolic functions. In this review, we describe the role of leptin in human physiology and review evidence from recent "proof of concept" clinical trials using recombinant human leptin in subjects with congenital leptin deficiency, hypoleptinemia associated with energy-deficient states, and hyperleptinemia associated with garden-variety obesity. Since most obese individuals are largely leptin-tolerant or -resistant, therapeutic uses of leptin are currently limited to patients with complete or partial leptin deficiency, including hypothalamic amenorrhea and lipoatrophy. Leptin administration in these energy-deficient states may help restore associated neuroendocrine, metabolic, and immune function and bone metabolism. Leptin treatment is currently available for individuals with congenital leptin deficiency and congenital lipoatrophy. The long-term efficacy and safety of leptin treatment in hypothalamic amenorrhea and acquired lipoatrophy are currently under investigation. Whether combination therapy with leptin and potential leptin sensitizers will prove effective in the treatment of garden-variety obesity and whether leptin may have a role in weight loss maintenance is being greatly anticipated.
Dardeno
Tina A
TA
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
Chou
Sharon H
SH
Moon
Hyun-Seuk
HS
Chamberland
John P
JP
Fiorenza
Christina G
CG
Mantzoros
Christos S
CS
D004734:Energy Metabolism / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007107:Immune System / Q000502:physiology; D020738:Leptin / Q000172:deficiency / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use*; D008659:Metabolic Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D008954:Models, Biological; D009490:Neurosecretory Systems / Q000502:physiology; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D012098:Reproduction / Q000502:physiology; D015398:Signal Transduction
D020738:Leptin