Ablation of uncoupling protein 3 affects interrelated factors leading to lipolysis and insulin resistance in visceral white adipose tissue.
endoplasmic reticulum
insulin resistance
lipolysis
mitochondria
uncoupling protein
white adipose tissue
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
08
04
2022
received:
25
11
2021
accepted:
11
04
2022
entrez:
22
4
2022
pubmed:
23
4
2022
medline:
27
4
2022
Statut:
ppublish
Résumé
The physiological role played by uncoupling protein 3 (UCP3) in white adipose tissue (WAT) has not been elucidated so far. In the present study, we evaluated the impact of the absence of the whole body UCP3 on WAT physiology in terms of ability to store triglycerides, oxidative capacity, response to insulin, inflammation, and adipokine production. Wild type (WT) and UCP3 Knockout (KO) mice housed at thermoneutrality (30°C) have been used as the animal model. Visceral gonadic WAT (gWAT) from KO mice showed an impaired capacity to store triglycerides (TG) as indicated by its lowered weight, reduced adipocyte diameter, and higher glycerol release (index of lipolysis). The absence of UCP3 reduces the maximal oxidative capacity of gWAT, increases mitochondrial free radicals, and activates ER stress. These processes are associated with increased levels of monocyte chemoattractant protein-1 and TNF-α. The response of gWAT to in vivo insulin administration, revealed by (ser473)-AKT phosphorylation, was blunted in KO mice, with a putative role played by eif2a, JNK, and inflammation. Variations in adipokine levels in the absence of UCP3 were observed, including reduced adiponectin levels both in gWAT and serum. As a whole, these data indicate an important role of UCP3 in regulating the metabolic functionality of gWAT, with its absence leading to metabolic derangement. The obtained results help to clarify some aspects of the association between metabolic disorders and low UCP3 levels.
Identifiants
pubmed: 35452152
doi: 10.1096/fj.202101816RR
doi:
Substances chimiques
Adipokines
0
Insulin
0
Triglycerides
0
Ucp3 protein, mouse
0
Uncoupling Protein 3
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22325Informations de copyright
© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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