Identification of functional lipid metabolism biomarkers of brown adipose tissue aging.
Aging
Brown adipose tissue
Ceramides
Dolichol lipids
Sphingolipids
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
10
12
2018
revised:
22
03
2019
accepted:
28
03
2019
pubmed:
21
4
2019
medline:
16
4
2020
entrez:
21
4
2019
Statut:
ppublish
Résumé
Aging is accompanied by loss of brown adipocytes and a decline in their thermogenic potential, which may exacerbate the development of adiposity and other metabolic disorders. Presently, only limited evidence exists describing the molecular alterations leading to impaired brown adipogenesis with aging and the contribution of these processes to changes of systemic energy metabolism. Samples of young and aged murine brown and white adipose tissue were used to compare age-related changes of brown adipogenic gene expression and thermogenesis-related lipid mobilization. To identify potential markers of brown adipose tissue aging, non-targeted proteomic and metabolomic as well as targeted lipid analyses were conducted on young and aged tissue samples. Subsequently, the effects of several candidate lipid classes on brown adipocyte function were examined. Corroborating previous reports of reduced expression of uncoupling protein-1, we observe impaired signaling required for lipid mobilization in aged brown fat after adrenergic stimulation. Omics analyses additionally confirm the age-related impairment of lipid homeostasis and reveal the accumulation of specific lipid classes, including certain sphingolipids, ceramides, and dolichols in aged brown fat. While ceramides as well as enzymes of dolichol metabolism inhibit brown adipogenesis, inhibition of sphingosine 1-phosphate receptor 2 induces brown adipocyte differentiation. Our functional analyses show that changes in specific lipid species, as observed during aging, may contribute to reduced thermogenic potential. They thus uncover potential biomarkers of aging as well as molecular mechanisms that could contribute to the degradation of brown adipocytes, thereby providing potential treatment strategies of age-related metabolic conditions.
Identifiants
pubmed: 31003944
pii: S2212-8778(18)31191-8
doi: 10.1016/j.molmet.2019.03.011
pmc: PMC6531832
pii:
doi:
Substances chimiques
Biomarkers
0
Ceramides
0
Dolichols
0
Proteome
0
Sphingolipids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-17Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.
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