Low Dose Leptin Administration Reverses Effects of Sustained Weight-Reduction on Energy Expenditure and Circulating Concentrations of Thyroid Hormones
Abstract
Maintenance of a reduced body weight is associated with decreased 24-hour energy expenditure, and decreased circulating concentrations of leptin and thyroid hormones. To determine whether these adaptive metabolic and endocrine changes are partly leptin-mediated, we measured body composition, aspects of energy expenditure, and circulating concentrations of leptin and thyroid hormones in 4 subjects at 3 time points: 1.) Usual body weight; 2.) While stable at 10% reduced body weight; and 3.) During a 5-week period at 10% reduced body weight while receiving twice per day leptin injections that restored 8 AM circulating leptin concentrations to those seen at usual body weight. During maintenance of a 10% reduced body weight, circulating T3, T4, and leptin concentrations were decreased. All of these endocrine changes were reversed by administration of “replacement” doses of leptin (r-metHuLeptin). Indirect calorimetry, and subtle changes in body composition associated with leptin administration, were used to calculate the net change in stored calories and in 24-hour energy expenditure. Total energy expenditure increased in all subjects during r-metHuLeptin administration. These data indicate that decrease leptin concentrations resulting from loss of fat mass account for some aspects of the endocrine/metabolic phenotype associated with the weight-reduced state.
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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 [42]
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Goyenechea, E., Parra, M. D., & Hernández, J. A. M. (2005) · Anales del Sistema Sanitario de Navarra · doi:10.4321/s1137-66272005000500007 · Cited by 11 · see citing works
Structures of human protein tyrosine phosphatase variants reveal targetable allosteric sites
Perdikari, A., Woods, V. A., Ebrahim, A., Lawler, K., Bounds, R., Shah, D. S., Singh, N. I., Mehlman, T. S., Riley, B. T., Sharma, S., et al. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.110852 · Cited by 7 · see citing works
Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons
Furigo, I. C., Teixeira, P. D., de, S. G. O., Couto, G. C. L., Romero, G. G., Perelló, M., Frazão, R., Elias, L. L. K., Metzger, M., List, E. O., et al. (2019) · Yearbook of pediatric endocrinology · doi:10.1530/ey.16.15.10 · Cited by 6 · see citing works
- Authors
- Rosenbaum, M., Murphy, E. M., Heymsfield, S. B., Matthews, D. E., & Leibel, R. L.
- Affiliations
- Columbia University (US)
- University of Vermont Medical Center (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2002-05-01
- Volume
- 87
- Issue
- 5
- Pages
- 2391-2394
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2044939881
- Cited by
- 407
- References
- 0
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 6 · 2023: 8 · 2022: 8 · 2021: 11 · 2020: 6 · 2019: 10 · 2018: 16 · 2017: 25 · 2016: 11 · 2015: 22 · 2014: 19 · 2013: 13 · 2012: 13
- FWCI
- 9.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk030583-18)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064773, DK-30583)
- National Center for Research Resources (RR 00645, M01RR000645)
- 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 replacement, weight loss, energy expenditure, thyroid hormones, T3, thyroxine, body composition, fat mass, metabolic adaptation, obesity, leptin deficiency
- MeSH terms
- Adult, Body Composition, Calorimetry, Indirect, Dose-Response Relationship, Drug, Energy Metabolism, Female, Humans, Male, Osmolar Concentration, Thyroid Hormones, Weight Loss, Leptin
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