Moderate SIRT1 overexpression protects against brown adipose tissue inflammation.
Adipocytes
/ metabolism
Adipocytes, Brown
/ metabolism
Adipose Tissue
/ metabolism
Adipose Tissue, Brown
/ metabolism
Animals
Energy Metabolism
Female
Gene Expression
/ genetics
Gene Expression Regulation
/ genetics
Inflammation
/ prevention & control
Insulin
/ metabolism
Insulin Resistance
/ physiology
Male
Mice
Mice, Inbred C57BL
Mitochondria
/ metabolism
Obesity
/ metabolism
Receptors, Adrenergic, beta
/ metabolism
Sirtuin 1
/ genetics
Thermogenesis
/ drug effects
Uncoupling Protein 1
/ metabolism
Brown adipose tissue
Inflammation
Insulin resistance
Sirtuin 1
Triiodothyronine
Uncoupling protein-1
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
17
07
2020
revised:
02
10
2020
accepted:
06
10
2020
pubmed:
14
10
2020
medline:
8
9
2021
entrez:
13
10
2020
Statut:
ppublish
Résumé
Metainflammation is a chronic low-grade inflammatory state induced by obesity and associated comorbidities, including peripheral insulin resistance. Brown adipose tissue (BAT), a therapeutic target against obesity, is an insulin target tissue sensitive to inflammation. Therefore, it is necessary to find strategies to protect BAT against the effects of inflammation in energy balance. In this study, we explored the impact of moderate sirtuin 1 (SIRT1) overexpression on insulin sensitivity and β-adrenergic responses in BAT and brown adipocytes (BA) under pro-inflammatory conditions. The effect of inflammation on BAT functionality was studied in obese db/db mice and lean wild-type (WT) mice or mice with moderate overexpression of SIRT1 (SIRT1 BAT from the db/db mice was susceptible to metabolic inflammation manifested by the activation of pro-inflammatory signaling cascades, increased pro-inflammatory gene expression, tissue-specific insulin resistance, and reduced UCP-1 expression. Impairment of insulin and noradrenergic responses were also found in the lean WT mice upon LPS injection. In contrast, BAT from the mice with moderate overexpression of SIRT1 (SIRT1 This study has ascertained the benefit of the moderate overexpression of SIRT1 to confer protection against defective insulin and β-adrenergic responses caused by BAT inflammation. Our results have potential therapeutic value in combinatorial therapies for BAT-specific thyromimetics and SIRT1 activators to combat metainflammation in this tissue.
Identifiants
pubmed: 33049408
pii: S2212-8778(20)30171-X
doi: 10.1016/j.molmet.2020.101097
pmc: PMC7600394
pii:
doi:
Substances chimiques
Insulin
0
Receptors, Adrenergic, beta
0
Uncoupling Protein 1
0
Sirt1 protein, mouse
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101097Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.
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