Cited by 593Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesHypothalamic control of reproductive hormones

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Leptin in human physiology and pathophysiology

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Mantzoros, Christos S., Magkos, Faidon, Brinkoetter, Mary, Sienkiewicz, Elizabeth, Dardeno, Tina A., Kim, Sang-Yong, Hamnvik, Ole-Petter R., Koniaris, Anastasia·2011·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00315.2011PMC PMC3191548

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Abstract

Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIV-related lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical applications of leptin or its analogs in human therapeutics.

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Overview
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Authors: Mantzoros, C. S., Magkos, F., Brinkoetter, M., Sienkiewicz, E., Dardeno, T. A., Kim, S.-Y., Hamnvik, O.-P. R., & Koniaris, A.
Affiliations: Beth Israel Deaconess Medical Center (US)
Brigham and Women's Hospital (US)
Corresponding author: Mantzoros, Christos S.
ORCID: Mantzoros, Christos S.
Magkos, Faidon
Kim, Sang-Yong
Hamnvik, Ole-Petter R.
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2011-10
Volume: 301
Issue: 4
Pages: E567-E584
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.00315.2011
PMC: PMC3191548
OpenAlex: W2010072332
Cited by: 593
References: 294
Citations by year: 2026: 18 · 2025: 21 · 2024: 37 · 2023: 30 · 2022: 46 · 2021: 31 · 2020: 42 · 2019: 40 · 2018: 39 · 2017: 40 · 2016: 39 · 2015: 34 · 2014: 64 · 2013: 58 · 2012: 50
FWCI: 5.92
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (R01DK079929, DK-081913, R01DK058785, R56DK058785, DK079929, DK 58785, K24DK081913)
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 deficiency, leptin resistance, hypothalamic amenorrhea, lipoatrophy, HIV-associated lipoatrophy, energy homeostasis, hypothalamic-pituitary axis, bone mineral density, insulin sensitivity, obesity, leptin therapy
MeSH terms: Adipose Tissue, Amenorrhea, Energy Metabolism, Female, Homeostasis, Humans, Hypothalamic Diseases, Hypothalamus, Male, Neurosecretory Systems, Reproduction, Leptin

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