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Adipocyte-specific Hnrnpa1 knockout aggravates obesity-induced metabolic dysfunction via upregulating of CCL2

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posted on 2024-02-06, 21:43 authored by Xiaoya Li, Yingying Su, Yiting Xu, Tingting Hu, Xuhong Lu, Jingjing Sun, Wenfei Li, Jian Zhou, Xiaojing Ma, Ying Yang, Yuqian Bao

Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) is involved in lipid and glucose metabolism via mRNA processing. However, whether and how HNRNPA1 alters adipocyte function in obesity remain obscure. Here, we found that obese state downregulated HNRNPA1 expression in white adipose tissue (WAT). The depletion of adipocyte HNRNPA1 promoted markedly increased macrophage infiltration, pro-inflammatory and fibrosis genes expression in WAT of obese mice, eventually leading to exacerbated insulin sensitivity, glucose tolerance, and hepatic steatosis. Mechanistically, HNRNPA1 interacted with Ccl2 and regulated its mRNA stability. Intraperitoneal injection of CCL2-CCR2 signaling antagonist improved adipose tissue inflammation and systemic glucose homeostasis. Furthermore, HNRNPA1 expression in human WAT was negatively correlated with BMI, fat percentage, and subcutaneous fat area. Among individuals with 1-year metabolic surgery follow-up, HNRNPA1 expression was positively related to percentage of total weight loss. These findings identify adipocyte HNRNPA1 as a link between adipose tissue inflammation and systemic metabolic homeostasis, which might be a promising therapeutic target for obesity related disorders.

Funding

This research was supported by the National Science Foundation of China (82200897, 82170889) and Shanghai Research Center for Endocrine and Metabolic Diseases (2022ZZ01002).

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