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Drug Insight: the role of leptin in human physiology and pathophysiology—emerging clinical applications
Abstract
Leptin is an adipocyte-secreted hormone with a key role in energy homeostasis. Studies in animal models, in humans with congenital complete leptin deficiency, and observational and interventional studies in humans with relative leptin deficiency (lower than normal leptin levels) have all indicated that leptin regulates multiple physiological functions, primarily in states of energy deficiency. This information led to proof-of-concept clinical trials involving leptin administration to individuals with relative or complete leptin deficiency. These conditions include congenital complete leptin deficiency, due to mutations in the leptin gene, and states of relative leptin deficiency including lipoatrophy and some forms of hypothalamic amenorrhea. Leptin, in replacement doses, normalizes neuroendocrine, metabolic and immune function in patients with these conditions, but further clinical studies are required to determine its long-term efficacy and safety. Management of leptin-deficient states with replacement doses of leptin holds promise as a therapeutic option. In addition, elucidation of the mechanisms underlying leptin resistance, which characterizes hyperleptinemic states such as human obesity and diabetes, might provide novel therapeutic targets for these prevalent clinical problems.
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In the citing paper
“Leptin concentrations are positively correlated with the amount of body fat (4-10).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [6]
In the citing paper
“However, although obese subjects are hyperleptinemic compared with lean persons (11), they appear either to be tolerant or resistant to the central hypothalamic effects of leptin.”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [6]
In the citing paper
“Leptin has been shown to have several effects on the innate immune system in leptin-deficient states: It exerts direct effects on macrophages by up-regulating the phagocytic activity, stimulates the secretion of proinflammatory cytokines, and stimulates chemotaxis in polymorphonuclear cells (6).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [6]
In the citing paper
“Similar to congenital leptin deficiency, relative leptin deficiency because of long-term energy deprivation is associated with defects in immunologic variables that may be corrected with exogenous r-metHuLeptin administration: Leptin replacement therapy alters circulating cytokine concentrations in women with hypothalamic amenorrhea who present with chronic relative leptin deficiency resulting”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [6]
In the citing paper
“These disturbances can be completely reversed by leptin administration (6).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [6]
In the citing paper
“A significant role of leptin in the regulation of the hypothalamicpituitary-thyroid axis has been well established in humans (6)(7)(8).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [6]
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Self-citation
Metadata
- Authors
- Brennan, A. M., & Mantzoros, C. S.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Mantzoros, Christos S
- Venue
- Nature Clinical Practice Endocrinology & Metabolism
- Published
- 2006-06
- Volume
- 2
- Issue
- 6
- Pages
- 318-327
- ISSN
- 1745-8366 (ISSN-L)
- 1745-8374
- OpenAlex
- W2036849525
- Semantic Scholar
- 39b64b226bdfa1ea79a07f8c094fba198c51d618
- Cited by
- 374
- References
- 82
- Citations by year
- 2025: 8 · 2024: 6 · 2023: 17 · 2022: 19 · 2021: 23 · 2020: 27 · 2019: 20 · 2018: 19 · 2017: 28 · 2016: 26 · 2015: 21 · 2014: 27 · 2013: 31 · 2012: 28
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Clinical Practice Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alexander von Humboldt-Stiftung
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 58785)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- leptin, leptin resistance, leptin deficiency, congenital leptin deficiency, lipoatrophy, hypothalamic amenorrhea, obesity, diabetes mellitus, energy homeostasis, leptin replacement therapy, neuroendocrine function, immune function
- MeSH terms
- Animals, Energy Metabolism, Humans, Immunity, Models, Biological, Neurosecretory Systems, Obesity, Leptin
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