Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency
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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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r-metHuLeptin administration has been found to increase FT4 and FT3 levels in leptin-deficient children and to reverse the decreased T3 and T4 levels in four subjects on a long-term hypocaloric diet.
“Although r-metHuLeptin administration has been found to increase FT4 and FT3 levels in leptin-deficient children (34) and to reverse the decreased T3 and T4 levels in four subjects on a long-term hypocaloric diet (42)”
From The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men (2003) · cites this paper as [34]
Immune function could be markedly improved with leptin replacement.
“However, immune function could be markedly improved with leptin replacement (29,30).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [29]
Leptin may increase circulating cytokine concentrations and regulate the T helper type 1 and 2 cell immune balance in states of congenital leptin deficiency and immune dysfunction.
“Thus, leptin may increase circulating cytokine concentrations and regulate the T helper type 1 and 2 cell immune balance in states of congenital leptin deficiency and immune dysfunction, supporting a role for leptin in regulating immune function in these conditions (29,30).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [29]
Children with congenital leptin deficiency given leptin have appropriately timed pubertal development.
“These children, when given leptin, have an appropriately timed pubertal development (28,29).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [29]
Leptin-deficient subjects respond dramatically to leptin administered in replacement doses, which induces markedly decreased appetite and food intake and results in a significant reduction in body weight.
“These leptindeficient subjects respond in a dramatic fashion to leptin administered in replacement doses, which induces markedly decreased appetite and food intake and which in turn result in a significant reduction in body weight (28)(29)(30).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [29]
In children with complete leptin deficiency who are still gaining weight and developing obesity, leptin replacement therapy can lead to substantial weight reduction.
“In children with complete leptin deficiency and who are still in the process of gaining weight and developing obesity, leptin replacement therapy can lead to substantial weight reduction (8, 9).”
From Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults (2004) · cites this paper as [9]
Previous studies had shown that leptin treatment can improve glucose homeostasis in patients with lipodystrophy and in children treated with leptin on a long-term basis.
“Previous studies had shown that leptin treatment can improve glucose homeostasis in patients with lipodystrophy (21) and in children treated with leptin on a long-term basis (8, 9).”
From Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults (2004) · cites this paper as [9]
In those children, leptin replacement reversed the effects of leptin deficiency, leading to puberty at an appropriate age.
“In those children, leptin replacement reversed the effects of leptin deficiency, leading to puberty at an appropriate age (8, 9).”
From Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults (2004) · cites this paper as [9]
The transient presence of antileptin antibodies has been noted in treatment of children with congenital leptin deficiency and adults with obesity.
“The transient presence of antileptin antibodies also has been noted in the past in treatment of children with congenital leptin de fi ciency (23, 24) and adults with obesity (25).”
From Leptin is an effective treatment for hypothalamic amenorrhea (2011) · cites this paper as [24]
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- Authors
- Farooqi, I. S., Matarese, G., Lord, G. M., Keogh, J. M., Lawrence, E., Agwu, C., Sanna, V., Jebb, S. A., Perna, F., Fontana, S., Lechler, R. I., DePaoli, A. M., & O’Rahilly, S.
- Affiliations
- Amgen (United States) (US)
- Institute for Experimental Endocrinology and Oncology (IT)
- Hammersmith Hospital (GB)
- University of Cambridge (GB)
- MRC Elsie Widdowson Laboratory (GB)
- Federico II University Hospital (IT)
- Corresponding author
- Farooqi, I. Sadaf
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2002-10-15
- Volume
- 110
- Issue
- 8
- Pages
- 1093-1103
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W4238663920
- Cited by
- 1,105
- References
- 39
- Citations by year
- 2026: 22 · 2025: 23 · 2024: 34 · 2023: 37 · 2022: 34 · 2021: 46 · 2020: 40 · 2019: 38 · 2018: 49 · 2017: 55 · 2016: 40 · 2015: 53 · 2014: 60 · 2013: 55 · 2012: 57
- FWCI
- 12.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Funders
- Amgen
- Wellcome Trust
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- leptin, congenital leptin deficiency, ob/ob mice, childhood obesity, T cell hyporesponsiveness, CD4+ T cells, thyroid hormones, gonadotropin secretion, pubertal development, hyperinsulinemia, hyperlipidemia, appetite, fat mass, neuroendocrine dysfunction, metabolic dysfunction
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