O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity
O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity
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DOI：
10.1038/s41467-019-13914-8
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发表时间：
2020-01-10
影响因子：
16.6
通讯作者：
Yang, Xiaoyong
中科院分区：
文献类型：
--
作者：
Yang, Yunfan;Fu, Minnie;Yang, Xiaoyong
过度的内脏脂肪积累是代谢不健康的肥胖和相关疾病的主要危险因素。内脏脂肪极易受到外部营养物质的影响。进入己糖胺生物合成途径的营养物质通量导致蛋白质被O-linked - n -乙酰氨基葡萄糖（O-GlcNAc）部分翻译后修饰。O-GlcNAc转移酶(OGT)负责将GlcNAc片段添加到靶蛋白上。在这里，我们报道脂肪OGT的诱导缺失通过特异性地促进内脏脂肪的脂肪分解导致内脏脂肪的快速减少。在机制上，内脏脂肪在禁食期间维持高水平的o - glcn酰化。OGT的缺失降低了脂滴相关的外周蛋白1 （PLIN1）的o - glcn酰化，从而导致PLIN1磷酸化升高和脂肪分解增强。此外，脂肪OGT过表达抑制脂肪分解，促进饮食引起的肥胖。这些发现确立了OGT在脂肪组织稳态中的重要作用，并指出了针对O-GlcNAc信号治疗肥胖的独特潜力。
Excessive visceral fat accumulation is a primary risk factor for metabolically unhealthy obesity and related diseases. The visceral fat is highly susceptible to the availability of external nutrients. Nutrient flux into the hexosamine biosynthetic pathway leads to protein posttranslational modification by O-linked beta-N-acetylglucosamine (O-GlcNAc) moieties. O-GlcNAc transferase (OGT) is responsible for the addition of GlcNAc moieties to target proteins. Here, we report that inducible deletion of adipose OGT causes a rapid visceral fat loss by specifically promoting lipolysis in visceral fat. Mechanistically, visceral fat maintains a high level of O-GlcNAcylation during fasting. Loss of OGT decreases O-GlcNAcylation of lipid droplet-associated perilipin 1 (PLIN1), which leads to elevated PLIN1 phosphorylation and enhanced lipolysis. Moreover, adipose OGT overexpression inhibits lipolysis and promotes diet-induced obesity. These findings establish an essential role for OGT in adipose tissue homeostasis and indicate a unique potential for targeting O-GlcNAc signaling in the treatment of obesity.