Adipose ZFP36 protects against diet-induced obesity and insulin resistance

作者：Yang Hu, Jinghan Hai, Yun Ti, Binghui Kong, Guoqing Yao, Yuan Zhao, Chen Zhang, Xuehui Zheng, Chunmei Zhang, Xiangping Ma, Huaitao Yu, Xiaoning Qin, Pavel Kovarik, Cheng Zhang, Shaozhuang Liu, Wencheng Zhang, Jingyuan Li, Peili Bu · 发表于：Metabolism · 年份：2025 · DOI：10.1016/j.metabol.2024.156131 · 被引用次数：11 · 研究领域：Adipose Tissue and Metabolism、Sirtuins and Resveratrol in Medicine、Lipid metabolism and biosynthesis

Aims Obesity, as a worldwide healthcare problem, has become more prevalent. ZFP36 is a well-known RNA-binding protein and involved in the posttranscriptional regulation of many physiological processes. Whether the adipose ZFP36 plays a role in obesity and insulin resistance remains unclear. Methods The expression levels of ZFP36 were analyzed in adipose tissues of obese patients, diet-induced obese mice, ob/ob mice and db/db mice. To determine whether adipose ZFP36 protects against the diet-induced obesity, we generated adipose-specific ZFP36 knockout (ZFP36 AKO ) mice, which were subjected to high-fat-diet (HFD) for 16 weeks. To explore the specific molecular mechanisms of ZFP36 regulating metabolic disorders, we used gene array assay of control and ZFP36-deficient adipose tissue, and assessed the pathways in vitro and vivo. Results Western blotting and RT-PCR were performed to determine the downregulating level of ZFP36 in adipose tissues of obese patients, diet-induced obese mice, ob/ob mice and db/db mice. Relative to control mice, ZFP36 AKO mice were more susceptible to HFD-induced obesity, along with insulin resistance, glucose tolerance, and increased metabolic disorders. The obesity of ZFP36 AKO mice was attributed to hypertrophy of adipocytes in white adipose tissue via decreased expression of Perilipin1 (PLIN1), adipose triglyceride lipase (ATGL), and hormone-sensitive lipase (HSL). We discovered that ZFP36 oppositely regulated RNF128 expression by repressing the mR...