Inflammation causes insulin resistance in mice via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels

Shuai Yan, Anna Santoro, Micah J. Niphakis, Antonio M. Pinto, Christopher L. Jacobs, Rasheed Ahmad, Radu M. Suciu, Bryan R. Fonslow, Rachel A. Herbst-Graham, Nhi Ngo, Cassandra L. Henry, Dylan M. Herbst, Alan Saghatelian, Barbara B. Kahn and Evan D. Rosen ()
Additional contact information
Shuai Yan: Beth Israel Deaconess Medical Center
Anna Santoro: Beth Israel Deaconess Medical Center
Micah J. Niphakis: Lundbeck La Jolla Research Center Inc.
Antonio M. Pinto: The Salk Institute for Biological Studies
Christopher L. Jacobs: Beth Israel Deaconess Medical Center
Rasheed Ahmad: Dasman Diabetes Institute
Radu M. Suciu: Lundbeck La Jolla Research Center Inc.
Bryan R. Fonslow: Lundbeck La Jolla Research Center Inc.
Rachel A. Herbst-Graham: Lundbeck La Jolla Research Center Inc.
Nhi Ngo: Lundbeck La Jolla Research Center Inc.
Cassandra L. Henry: Lundbeck La Jolla Research Center Inc.
Dylan M. Herbst: Lundbeck La Jolla Research Center Inc.
Alan Saghatelian: The Salk Institute for Biological Studies
Barbara B. Kahn: Beth Israel Deaconess Medical Center
Evan D. Rosen: Beth Israel Deaconess Medical Center

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Obesity-induced inflammation causes metabolic dysfunction, but the mechanisms remain elusive. Here we show that the innate immune transcription factor interferon regulatory factor (IRF3) adversely affects glucose homeostasis through induction of the endogenous FAHFA hydrolase androgen induced gene 1 (AIG1) in adipocytes. Adipocyte-specific knockout of IRF3 protects male mice against high-fat diet-induced insulin resistance, whereas overexpression of IRF3 or AIG1 in adipocytes promotes insulin resistance on a high-fat diet. Furthermore, pharmacological inhibition of AIG1 reversed obesity-induced insulin resistance and restored glucose homeostasis in the setting of adipocyte IRF3 overexpression. We, therefore, identify the adipocyte IRF3/AIG1 axis as a crucial link between obesity-induced inflammation and insulin resistance and suggest an approach for limiting the metabolic dysfunction accompanying obesity.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-48220-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48220-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-48220-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().