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Published on: September 9, 2025
Leptin in human physiology and therapeutics
Tina A Dardeno1, Sharon H Chou, Hyun-Seuk Moon
1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
Leptin, a key hormone for energy balance, is effective for treating leptin deficiency. However, most obese individuals show leptin resistance, limiting its use in general obesity treatment.
Area of Science:
- Endocrinology
- Metabolic Regulation
- Human Physiology
Background:
- Leptin is a crucial hormone regulating energy homeostasis, impacting reproductive, neuroendocrine, immune, and metabolic functions.
- Recent clinical trials explore recombinant human leptin for conditions like congenital leptin deficiency, hypoleptinemia, and hyperleptinemia in obesity.
- Most obese individuals exhibit leptin tolerance or resistance, complicating therapeutic applications.
Purpose of the Study:
- To review the physiological role of leptin in humans.
- To examine clinical trial evidence for recombinant human leptin therapy.
- To assess leptin's therapeutic potential in various deficiency and resistance states.
Main Methods:
- Review of existing literature and clinical trial data on leptin therapy.
- Analysis of leptin's effects in congenital leptin deficiency, hypoleptinemia, and hyperleptinemia.
- Evaluation of leptin's impact on neuroendocrine, metabolic, immune, and bone functions.
Main Results:
- Leptin therapy is currently limited to patients with complete or partial leptin deficiency (e.g., congenital leptin deficiency, lipoatrophy, hypothalamic amenorrhea).
- Leptin administration can restore functions in energy-deficient states.
- Efficacy and safety of leptin in hypothalamic amenorrhea and acquired lipoatrophy are under investigation.
Conclusions:
- Leptin is a viable treatment for specific leptin deficiency disorders.
- Leptin resistance in common obesity presents a significant therapeutic challenge.
- Future research may explore combination therapies for obesity and weight management.
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