Antimicrobial protein REG3A regulates glucose homeostasis and insulin resistance in obese diabetic mice.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
15 03 2023
15 03 2023
Historique:
received:
29
05
2022
accepted:
21
02
2023
entrez:
15
3
2023
pubmed:
16
3
2023
medline:
17
3
2023
Statut:
epublish
Résumé
Innate immune mediators of pathogen clearance, including the secreted C-type lectins REG3 of the antimicrobial peptide (AMP) family, are known to be involved in the regulation of tissue repair and homeostasis. Their role in metabolic homeostasis remains unknown. Here we show that an increase in human REG3A improves glucose and lipid homeostasis in nutritional and genetic mouse models of obesity and type 2 diabetes. Mice overexpressing REG3A in the liver show improved glucose homeostasis, which is reflected in better insulin sensitivity in normal weight and obese states. Delivery of recombinant REG3A protein to leptin-deficient ob/ob mice or wild-type mice on a high-fat diet also improves glucose homeostasis. This is accompanied by reduced oxidative protein damage, increased AMPK phosphorylation and insulin-stimulated glucose uptake in skeletal muscle tissue. Oxidative damage in differentiated C2C12 myotubes is greatly attenuated by REG3A, as is the increase in gp130-mediated AMPK activation. In contrast, Akt-mediated insulin action, which is impaired by oxidative stress, is not restored by REG3A. These data highlight the importance of REG3A in controlling oxidative protein damage involved in energy and metabolic pathways during obesity and diabetes, and provide additional insight into the dual function of host-immune defense and metabolic regulation for AMP.
Identifiants
pubmed: 36918710
doi: 10.1038/s42003-023-04616-5
pii: 10.1038/s42003-023-04616-5
pmc: PMC10015038
doi:
Substances chimiques
AMP-Activated Protein Kinases
EC 2.7.11.31
Glucose
IY9XDZ35W2
Insulin
0
Anti-Infective Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
269Informations de copyright
© 2023. The Author(s).
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