Drug Insight: the role of leptin in human physiology and pathophysiology—emerging clinical applications

Brennan, Aoife M; Mantzoros, Christos S

doi:10.1038/ncpendmet0196

Cited by 376Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesHypothalamic control of reproductive hormones

Drug Insight: the role of leptin in human physiology and pathophysiology—emerging clinical applications

Brennan, Aoife M, Mantzoros, Christos S·2006·Nature Clinical Practice Endocrinology & Metabolism

DOI 10.1038/ncpendmet0196

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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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Leptin concentrations are positively correlated with the amount of body fat.
“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]
Obese subjects appear either tolerant or resistant to the central hypothalamic effects of leptin.
“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]
Leptin has several effects on the innate immune system in leptin-deficient states: it exerts direct effects on macrophages by up-regulating phagocytic activity, stimulates the secretion of proinflammatory cytokines, and stimulates chemotaxis in polymorphonuclear cells.
“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]
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.
“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]
These disturbances can be completely reversed by leptin administration.
“These disturbances can be completely reversed by leptin administration (6).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [6]

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Elmquist (1998) · doi:10.1002/(sici)1096-9861(19980615)395:4

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Authors: Brennan, A. M., & Mantzoros, C. S.
Affiliations: Beth Israel Deaconess Medical Center (US)
Corresponding author: Mantzoros, Christos S
ORCID: Brennan, Aoife M
Mantzoros, Christos S
Venue: Nature Clinical Practice Endocrinology & Metabolism
Publisher: Springer Science and Business Media LLC
Published: 2006-06
Volume: 2
Issue: 6
Pages: 318-327
ISSN: 1745-8366 (ISSN-L)
1745-8374
DOI: 10.1038/ncpendmet0196
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 › Epidemiology › 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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Drug Insight: the role of leptin in human physiology and pathophysiology—emerging clinical applications

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