Dataset Information

The role of IRAKM in IL-1β-treated adipocytes

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Adipocyte

DISEASE(S): Obesity

SUBMITTER: Ling Li

LAB HEAD: Xiaoxia Li

PROVIDER: PXD031934 | Pride | 2022-06-09

REPOSITORIES: Pride

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IL-1R-IRAKM-Slc25a1 signaling axis reprograms lipogenesis in adipocytes to promote diet-induced obesity in mice.

Liu Weiwei W Zhou Hao H Wang Han H Zhang Quanri Q Zhang Renliang R Willard Belinda B Liu Caini C Kang Zizhen Z Li Xiao X Li Xiaoxia X

Nature communications 20220518 1

Toll-like receptors/Interleukin-1 receptor signaling plays an important role in high-fat diet-induced adipose tissue dysfunction contributing to obesity-associated metabolic syndromes. Here, we show an unconventional IL-1R-IRAKM-Slc25a1 signaling axis in adipocytes that reprograms lipogenesis to promote diet-induced obesity. Adipocyte-specific deficiency of IRAKM reduces high-fat diet-induced body weight gain, increases whole body energy expenditure and improves insulin resistance, associated w ...[more]

PMID: 35585086

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			Action	DRS
	IRAKM-0hr.mzML	Mzml
	IRAKM-0hr.mzid.gz	Mzid
	IRAKM-0hr.raw	Raw
	IRAKM-1hr.mzML	Mzml
	IRAKM-1hr.mzid.gz	Mzid