Non-hematopoietic IL-4Rα expression contributes to fructose-driven obesity and metabolic sequelae.
Journal
International journal of obesity (2005)
ISSN: 1476-5497
Titre abrégé: Int J Obes (Lond)
Pays: England
ID NLM: 101256108
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
19
10
2020
accepted:
30
06
2021
revised:
23
06
2021
pubmed:
25
7
2021
medline:
2
2
2022
entrez:
24
7
2021
Statut:
ppublish
Résumé
The risks of excess sugar intake in addition to high-fat diet consumption on immunopathogenesis of obesity-associated metabolic diseases are poorly defined. Interleukin-4 (IL-4) and IL-13 signaling via IL-4Rα regulates adipose tissue lipolysis, insulin sensitivity, and liver fibrosis in obesity. However, the contribution of IL-4Rα to sugar rich diet-driven obesity and metabolic sequelae remains unknown. WT, IL-4Rα-deficient (IL-4Rα We show that IL-4Rα regulated HF + HC diet-driven weight gain, whole body adiposity, adipose tissue inflammatory gene expression, energy expenditure, locomotor activity, glucose metabolism, hepatic steatosis, hepatic inflammatory gene expression and hepatocellular damage. These effects were potentially, and in part, dependent on non-hematopoietic IL-4Rα expression but were independent of direct STAT6 activation. Mechanistically, hepatic ketohexokinase-A and C expression was dependent on IL-4Rα, as it was reduced in IL-4Rα-deficient mice. KHK activity was also affected by HF + HC dietary challenge. Further, reduced expression/activity of KHK in IL-4Rα mice had a significant effect on fatty acid oxidation and fatty acid synthesis pathways. Our findings highlight potential contribution of non-hematopoietic IL-4Rα activation of a non-canonical signaling pathway that regulates the HF + HC diet-driven induction of obesity and severity of obesity-associated sequelae.
Identifiants
pubmed: 34302121
doi: 10.1038/s41366-021-00902-6
pii: 10.1038/s41366-021-00902-6
pmc: PMC8528699
doi:
Substances chimiques
Interleukin-4
207137-56-2
Fructose
30237-26-4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2377-2387Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK078392
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM083204
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM063483
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK099222
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI118697
Pays : United States
Informations de copyright
© 2021. The Author(s).
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