Leptin-Mediated Changes in the Human Metabolome.

Details

Serval ID
serval:BIB_0D8CE0E0C9EE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Leptin-Mediated Changes in the Human Metabolome.
Journal
The Journal of clinical endocrinology and metabolism
Author(s)
Lawler K., Huang-Doran I., Sonoyama T., Collet T.H., Keogh J.M., Henning E., O'Rahilly S., Bottolo L., Farooqi I.S.
ISSN
1945-7197 (Electronic)
ISSN-L
0021-972X
Publication state
Published
Issued date
01/08/2020
Peer-reviewed
Oui
Volume
105
Number
8
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
While severe obesity due to congenital leptin deficiency is rare, studies in patients before and after treatment with leptin can provide unique insights into the role that leptin plays in metabolic and endocrine function.
The aim of this study was to characterize changes in peripheral metabolism in people with congenital leptin deficiency undergoing leptin replacement therapy, and to investigate the extent to which these changes are explained by reduced caloric intake.
Ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) was used to measure 661 metabolites in 6 severely obese people with congenital leptin deficiency before, and within 1 month after, treatment with recombinant leptin. Data were analyzed using unsupervised and hypothesis-driven computational approaches and compared with data from a study of acute caloric restriction in healthy volunteers.
Leptin replacement was associated with class-wide increased levels of fatty acids and acylcarnitines and decreased phospholipids, consistent with enhanced lipolysis and fatty acid oxidation. Primary and secondary bile acids increased after leptin treatment. Comparable changes were observed after acute caloric restriction. Branched-chain amino acids and steroid metabolites decreased after leptin, but not after acute caloric restriction. Individuals with severe obesity due to leptin deficiency and other genetic obesity syndromes shared a metabolomic signature associated with increased BMI.
Leptin replacement was associated with changes in lipolysis and substrate utilization that were consistent with negative energy balance. However, leptin's effects on branched-chain amino acids and steroid metabolites were independent of reduced caloric intake and require further exploration.
Keywords
bile acids, leptin, lipids, metabolomics, obesity
Pubmed
Web of science
Open Access
Yes
Create date
15/06/2020 14:35
Last modification date
14/10/2020 5:23
Usage data