The DOI matches its Crossref record; 293 of the 294 references it cites were found in a registry or an index.
Leptin in human physiology and pathophysiology
Open accessAbstract
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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“Leptin is an adipokine that acts as a satiety signal, and can directly or indirectly improve insulin sensitivity and reduce lipids and visceral adiposity [28].”
From Impact of Five Nights of Sleep Restriction on Glucose Metabolism, Leptin and Testosterone in Young Adult Men (2012) · cites this paper as [28]
In the citing paper
“It regulates food intake, metabolism, energy expenditure, and body weight (11).”
From Sparse System Identification of Leptin Dynamics in Women With Obesity (2022) · cites this paper as [11]
In the citing paper
“Hence, excessive amounts of adipose tissue in the body correspond to an increase in leptin production rate, and thus, higher serum leptin levels (11).”
From Sparse System Identification of Leptin Dynamics in Women With Obesity (2022) · cites this paper as [11]
In the citing paper
“Leptin is a hormone produced and secreted primarily by adipocytes.”
From Sparse System Identification of Leptin Dynamics in Women With Obesity (2022) · cites this paper as [11]
In the citing paper
“Leptin is a signaling hormone and adipokine that is essential to activating central nervous system (CNS) networks involved in the suppression of appetite.”
From Sparse System Identification of Leptin Dynamics in Women With Obesity (2022) · cites this paper as [11]
Citations
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602013340503 · Cited by 6,326
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915
Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451
Effects of the obese Gene Product on Body Weight Regulation in ob / ob Mice
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995) · Science · doi:10.1126/science.7624776 · Cited by 4,017
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Özcan, U., Cao, Q., Yilmaz, E., Lee, A.-H., Iwakoshi, N. N., Özdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., & Hotamisligil, G. S. (2004) · Science · doi:10.1126/science.1103160 · Cited by 3,844
Role of leptin in the neuroendocrine response to fasting
Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996) · Nature · doi:10.1038/382250a0 · Cited by 3,117
Self-citationThe GPR54 Gene as a Regulator of Puberty
Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa035322 · Cited by 2,557
Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54
de Roux, N., Genin, E., Carel, J.-C., Matsuda, F., Chaussain, J.-L., & Milgrom, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834399100 · Cited by 2,431
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley, M. A., Smart, J. L., Rubinstein, M., Cerdán, M. G., Diano, S., Horvath, T. L., Cone, R. D., & Low, M. J. (2001) · Nature · doi:10.1038/35078085 · Cited by 2,356
Research works printed but not linked: 24
- Aronis KN, J Clin Endocrinol Metab
- Boden G, 1996, J Clin Endocrinol Metab, 81, 3419
- 10.1172/JCI200317490 · DOI · Paper page
- Einollahi N, 2010, Acta Med Iran, 48, 300
- Farooqi S, 2007, Horm Res, 68, 5
- Fogteloo AJ, 2003, Diabetes Nutr Metab, 16, 109
- Jimerson DC, 2000, J Clin Endocrinol Metab, 85, 4511
- Kelesidis T, 2006, Pediatr Endocrinol Rev, 3, 239
- 10.1210/endo.138.6.5209 · DOI · Paper page
- Licinio J, 1998, J Clin Endocrinol Metab, 83, 4140
- Lin KC, 2000, Kaohsiung J Med Sci, 16, 13
- Mantzoros C, 1997, J Clin Endocrinol Metab, 82, 1845
- Mantzoros CS, 2000, J Clin Endocrinol Metab, 85, 4000
- Mantzoros CS, 1997, J Clin Endocrinol Metab, 82, 1066
- Mantzoros CS, 1997, J Clin Endocrinol Metab, 82, 3408
- 10.1210/jcem.86.7.7644 · DOI · Paper page
- Miller KK, 1998, J Clin Endocrinol Metab, 83, 2309
- Pardini VC, 1998, J Clin Endocrinol Metab, 83, 503
- Pombo M, 2001, Horm Res, 55, 11
- Rosenbaum M, 1996, J Clin Endocrinol Metab, 81, 3424
- Rosenbaum M, 2008, J Clin Invest, 118, 2583
- Saad MF, 1997, J Clin Endocrinol Metab, 82, 579
- Seufert J, 1999, J Clin Endocrinol Metab, 84, 670
- van der Kroon PH, 1982, Int J Obes, 6, 83
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Metabolic Regulation of T Lymphocytes
MacIver, N. J., Michalek, R. D., & Rathmell, J. C. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095956 · Cited by 1,244
Adipokines in health and disease
Fasshauer, M., & Blüher, M. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.04.014 · Cited by 1,050
Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism
Park, H. K., & Ahima, R. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.08.004 · Cited by 710
Hu, M. C., Shiizaki, K., Kuro-o, M., & Moe, O. W. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183727 · Cited by 587
Leptin signaling and leptin resistance
Zhou, Y., & Rui, L. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0263-5 · Cited by 358
Metadata
- 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.
- 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
- 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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