12-Lipoxygenase Regulates Cold Adaptation and Glucose Metabolism by Producing the Omega-3 Lipid 12-HEPE from Brown Fat.
12-HEPE
adipocytes
brown adipose tissue
diabetes
eicosapentaenoic acid
fat
lipidomic
lipokine
obesity
thermogenesis
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
received:
12
07
2018
revised:
12
03
2019
accepted:
01
07
2019
pubmed:
30
7
2019
medline:
4
9
2020
entrez:
30
7
2019
Statut:
ppublish
Résumé
Distinct oxygenases and their oxylipin products have been shown to participate in thermogenesis by mediating physiological adaptations required to sustain body temperature. Since the role of the lipoxygenase (LOX) family in cold adaptation remains elusive, we aimed to investigate whether, and how, LOX activity is required for cold adaptation and to identify LOX-derived lipid mediators that could serve as putative cold mimetics with therapeutic potential to combat diabetes. By utilizing mass-spectrometry-based lipidomics in mice and humans, we demonstrated that cold and β3-adrenergic stimulation could promote the biosynthesis and release of 12-LOX metabolites from brown adipose tissue (BAT). Moreover, 12-LOX ablation in mouse brown adipocytes impaired glucose uptake and metabolism, resulting in blunted adaptation to the cold in vivo. The cold-induced 12-LOX product 12-HEPE was found to be a batokine that improves glucose metabolism by promoting glucose uptake into adipocytes and skeletal muscle through activation of an insulin-like intracellular signaling pathway.
Identifiants
pubmed: 31353262
pii: S1550-4131(19)30374-2
doi: 10.1016/j.cmet.2019.07.001
pmc: PMC6774888
mid: NIHMS1534333
pii:
doi:
Substances chimiques
Alox12b protein, mouse
EC 1.13.11.31
Arachidonate 12-Lipoxygenase
EC 1.13.11.31
ALOX12 protein, human
EC 1.13.11.31.
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
768-783.e7Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL106173
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK102898
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS087165
Pays : United States
Organisme : NIGMS NIH HHS
ID : P01 GM095467
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK099511
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007260
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK036836
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK077097
Pays : United States
Organisme : NHLBI NIH HHS
ID : F32 HL136044
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK111714
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32 DK102320
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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