Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy.
autonomic nervous system
energy expenditure
leptin
lipodystrophy
thyroid hormone
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
27 09 2021
27 09 2021
Historique:
received:
10
02
2021
pubmed:
24
4
2021
medline:
17
11
2021
entrez:
23
4
2021
Statut:
ppublish
Résumé
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. To determine the effects of metreleptin on EE in patients with lipodystrophy. Nonrandomized crossover study of 25 patients with lipodystrophy (National Institutes of Health, 2013-2018). 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. 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. 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. 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.
Identifiants
pubmed: 33890058
pii: 6247344
doi: 10.1210/clinem/dgab269
pmc: PMC8475236
doi:
Substances chimiques
Leptin
0
Thyroid Hormones
0
metreleptin
TL60C27RLH
Banques de données
ClinicalTrials.gov
['NCT01778556']
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e4163-e4178Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK071013
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA DK075084
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK075084-08
Pays : United States
Informations de copyright
Published by Oxford University Press on behalf of the Endocrine Society 2021.
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