PXD031934

PXD031934 is an original dataset announced via ProteomeXchange.

Title	The role of IRAKM in IL-1β-treated adipocytes
Description	Toll-like receptors/Interleukin-1 receptor (IL-1R) signaling plays an important role in High-fat diet (HFD)-induced adipose tissue dysfunction contributing to obesity-associated metabolic syndromes. Here, we show an unconventional IL-1R-IRAKM (IL-1R-associated kinase M)-Slc25a1 signaling axis in adipocytes that reprograms lipogenesis to promote diet-induced obesity. Adipocyte-specific deficiency of IRAKM reduced HFD-induced body weight gain, increased whole body energy expenditure and improved insulin resistance, associated with decreased lipid accumulation and adipocyte cell sizes. IL-1β stimulation induced the translocation of IRAKM Myddosome to mitochondria to promote de novo lipogenesis in adipocytes. Mechanistically, IRAKM interacts with and phosphorylates mitochondrial citrate carrier Slc25a1 to promote IL-1β-induced mitochondrial citrate transport to cytosol and de novo lipogenesis. Moreover, IRAKM-Slc25a1 axis mediates IL-1β induced Pgc1a acetylation to regulate thermogenic gene expression in adipocytes. IRAKM kinase-inactivation also attenuated HFD-induced obesity. Taken together, our study suggests that the IL-1R-IRAKM-Slc25a1 signaling axis tightly links inflammation and adipocyte metabolism, indicating a novel therapeutic target for obesity.
HostingRepository	PRIDE
AnnounceDate	2022-06-09
AnnouncementXML	Submission_2022-06-09_08:27:16.877.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD031934
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ling Li
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-28 03:33:07	ID requested
⏵ 1	2022-06-09 08:27:17	announced

Liu W, Zhou H, Wang H, Zhang Q, Zhang R, Willard B, Liu C, Kang Z, Li X, Li X, IL-1R-IRAKM-Slc25a1 signaling axis reprograms lipogenesis in adipocytes to promote diet-induced obesity in mice. Nat Commun, 13(1):2748(2022) [pubmed]

submitter keyword: IRAKM, Slc25a1, fatty acid synthesis, Pgc1a acetylation, adipocytes

Xiaoxia Li
contact affiliation	Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA
contact email	lix@ccf.org
lab head
Ling Li
contact affiliation	Cleveland Clinic
contact email	lil5@ccf.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031934
     1. Label: PRIDE project
     2. Name: The role of IRAKM in IL-1β-treated adipocytes