Heat shock factor 1 in fat biology: <i>comments on ‘Local hyperthermia therapy induces browning of white fat and treats obesity’</i>

Xu, Lingyan; Li, Yu; Zhang, Yankang; Zhang, Ting; Wang, Dongmei; Ma, Xinran

doi:10.1093/jmcb/mjac026

Cited by 1 publication

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References 10 publications

(12 reference statements)

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“…It has recently been reported that A2B1 plays an important role in antiviral innate immune responses by recognizing viral DNA, which initiates type I interferon production and promotes nucleus exportation of mRNAs of viral DNA sensors cGAMP synthase (cGAS) stimulator of interferon genes (STING) for amplification of antiviral immune responses [ 10 ]. We have previously shown the involvement of A2B1 in obesity and metabolic diseases by regulating mRNA stability of mitochondrial and thermogenic gene programs in inguinal fat (iWAT) [ 11 , 12 , 13 ]. As obesity features low-grade chronic inflammation, these previous studies indicated a critical role of A2B1 in immune homeostasis, during which process, macrophages are indispensable.…”

Section: Introductionmentioning

confidence: 99%

HnRNPA2B1 Aggravates Inflammation by Promoting M1 Macrophage Polarization

et al. 2023

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Macrophages have critical contributions to both acute and chronic inflammatory diseases, for example, bowel disease and obesity, respectively. However, little is known about the post-transcriptional regulatory mechanisms in macrophage-mediated inflammatory diseases. hnRNPA2B1 (A2B1) is an RNA binding protein for mRNA fate determination. We showed that hnRNPA2B1 mRNA levels were increased in colon in dextran sodium sulfate (DSS)-induced colitis mice and in epididymal white adipose tissue (eWAT) and spleen of high-fat-diet (HFD)-induced obese mice. Consistently, mice with haploinsufficiency of A2B1 (A2B1 HET) are protected against DSS-induced acute colitis and HFD-induced obesity, with decreased M1 macrophages polarization in colon, eWAT and spleen. Mechanistically, A2B1 mRNA and protein levels were increased in LPS-stimulated RAW 264.7 macrophages, and A2B1 enhanced RNA stability of pro-inflammatory genes Tnfα, Il-6 and Il-1β for the regulation of macrophages polarization. Interestingly, A2B1 HET mice exhibited reduced white fat expansion, which was influenced by macrophages, since conditioned medium from macrophages with A2B1 manipulation significantly changed preadipocyte proliferation. Our data demonstrate that A2B1 plays a vital role in macrophage-mediated inflammation via regulating mRNA stability, suggesting that A2B1 may be served as a promising target for the intervention of acute and chronic inflammatory diseases.

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