USF-LVHN SELECT
Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy.
Publication/Presentation Date
9-27-2021
Abstract
CONTEXT: Leptin is an adipokine that signals energy sufficiency. In rodents, leptin deficiency decreases energy expenditure (EE), which is corrected following leptin replacement. In humans, data are mixed regarding leptin-mediated effects on EE.
OBJECTIVE: To determine the effects of metreleptin on EE in patients with lipodystrophy.
DESIGN, SETTING, AND PATIENTS: Nonrandomized crossover study of 25 patients with lipodystrophy (National Institutes of Health, 2013-2018).
INTERVENTION: The initiation cohort consisted of 17 patients without prior exposure to metreleptin, studied before and after 14 days of metreleptin. The withdrawal cohort consisted of 8 previously metreleptin-treated patients, studied before and after 14 days of metreleptin withdrawal.
MAIN OUTCOMES: 24-h total energy expenditure (TEE), resting energy expenditure (REE), autonomic nervous system activity [heart rate variability (HrV)], plasma-free triiodothyronine (T3), free thyroxine (T4), epinephrine, norepinephrine, and dopamine.
RESULTS: In the initiation cohort, TEE and REE decreased by 5.0% (121 ± 152 kcal/day; P = 0.006) and 5.9% (120 ± 175 kcal/day; P = 0.02). Free T3 increased by 19.4% (40 ± 49 pg/dL; P = 0.01). No changes in catecholamines or HrV were observed. In the withdrawal cohort, free T3 decreased by 8.0% (P = 0.04), free T4 decreased by 11.9% (P = 0.002), and norepinephrine decreased by 34.2% (P = 0.03), but no changes in EE, epinephrine, dopamine, or HrV were observed.
CONCLUSIONS: Metreleptin initiation decreased EE in patients with lipodystrophy, but no changes were observed after metreleptin withdrawal. Thyroid hormone was higher on metreleptin in both initiation and withdrawal cohorts. Decreased EE after metreleptin in lipodystrophy may result from reductions in energy-requiring metabolic processes that counteract increases in EE via adipose tissue-specific neuroendocrine and adrenergic signaling.
Volume
106
Issue
10
First Page
4163
Last Page
4163
ISSN
1945-7197
Published In/Presented At
Grover, A., Quaye, E., Brychta, R. J., Christensen, J., Startzell, M. S., Meehan, C. A., Valencia, A., Marshall, B., Chen, K. Y., & Brown, R. J. (2021). Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy. The Journal of clinical endocrinology and metabolism, 106(10), e4163–e4178. https://doi.org/10.1210/clinem/dgab269
Disciplines
Medical Education | Medicine and Health Sciences
PubMedID
33890058
Department(s)
USF-LVHN SELECT Program, USF-LVHN SELECT Program Students
Document Type
Article