TRIM59 deficiency aggravates HFD-induced obesity in mice associated with increased adipose tissue inflammation, lipid accumulation, and apoptosis

IF 4.4 2区 生物学 Q2 CELL BIOLOGY
Yinni Chen , Xiangnuo Han , Tongzhan Liu , Yuqi Ni , Xinxin Deng , Wenhan Wei , Meixiu Jiang
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引用次数: 0

Abstract

TRIM59 (tripartite motif-containing 59) is involved in many pathological processes including inflammation and tumorigenesis. However, the effect of TRIM59 on obesity remains unknown. In this study, we aimed to investigate the role of TRIM59 in obesity and clarify the involved mechanisms. Our results showed that TRIM59 expression was significantly decreased in fat from high-fat diet (HFD)-induced obese mice. The TRIM59+/− mice with HFD showed increased body weight and white adipose tissue (WAT) weight, larger adipocyte sizes, and increased adipose tissue inflammation with the elevated expression of pro-inflammatory cytokines including TNF-α, IL-1β and IL-6 accompanied by an increased macrophage infiltration. Moreover, TRIM59 knockdown increased the serum levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Mechanistically, TRIM59 knockdown is associated with heightened activation of TLR4/JNK-p38/NF-κB signaling pathways to promote inflammation, increase adipogenesis and lipogenesis related genes while decreased lipolysis and β-oxidation related genes expression to increase lipid accumulation, simultaneously increased Bax and caspase 3 while decreased Bcl-2 expression to induce apoptosis, thereby leading to obesity. Taken together, our findings define a new critical biological role of TRIM59 in the regulation of diet-induced obesity through attenuating inflammation, improving lipid metabolism and apoptosis, and we conclude that TRIM59 may provide a novel insight in therapeutic target research for treatment of obesity-associated metabolic diseases.
TRIM59缺乏会加重小鼠hfd诱导的肥胖,与脂肪组织炎症、脂质积累和细胞凋亡增加有关
TRIM59 (tripartite motif-containing 59)参与了包括炎症和肿瘤发生在内的许多病理过程。然而,TRIM59对肥胖的影响尚不清楚。在本研究中,我们旨在探讨TRIM59在肥胖中的作用并阐明其相关机制。我们的研究结果表明,TRIM59在高脂饮食(HFD)诱导的肥胖小鼠的脂肪中表达显著降低。TRIM59+/−HFD小鼠表现为体重和白色脂肪组织(WAT)重量增加,脂肪细胞大小增大,脂肪组织炎症增加,促炎因子TNF-α、IL-1β和IL-6表达升高,巨噬细胞浸润增加。此外,TRIM59敲低增加了血清甘油三酯(TG)、总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)水平。机制上,TRIM59敲低与TLR4/JNK-p38/NF-κB信号通路激活增加,促进炎症,增加脂肪生成和脂肪生成相关基因,降低脂肪分解和β-氧化相关基因表达,增加脂质积累,同时增加Bax和caspase 3,降低Bcl-2表达,诱导细胞凋亡,从而导致肥胖。综上所述,我们的研究结果确定了TRIM59通过减轻炎症、改善脂质代谢和细胞凋亡来调节饮食性肥胖的新的关键生物学作用,我们得出结论,TRIM59可能为治疗肥胖相关代谢疾病的治疗靶点研究提供新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cellular signalling
Cellular signalling 生物-细胞生物学
CiteScore
8.40
自引率
0.00%
发文量
250
审稿时长
27 days
期刊介绍: Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.
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