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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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“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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Leptin and Obesity: Role and clinical implication.
Obradovic, M., Sudar-Milovanovic, E., Soskic, S., Essack, M., Arya, S., Stewart, A. J., Gojobori, T., & Isenovic, E. R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.585887 · Cited by 1,121
Metadata
- 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 › Endocrinology, Diabetes and Metabolism › 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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