ADAR1 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice.
ADAR1 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice.
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ADAR1 缺陷可防止小鼠高脂饮食引起的肥胖和胰岛素抵抗。
DOI：
10.1152/ajpendo.00175.2020
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Chen,Shi-You
中科院分区：
文献类型：
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作者：
Cui,Xiao-Bing;Fei,Jia;Chen,Sisi;Edwards,GaylenL;Chen,Shi-You
肥胖是2型糖尿病、心血管疾病和许多其他慢性疾病的重要独立危险因素。本研究的目的是确定腺苷脱氨酶作用于RNA 1（ADAR 1）在肥胖和胰岛素抵抗的发展中的作用。野生型（WT）和杂合子ADAR 1缺陷型（Adar 1 +/−）小鼠喂食正常食物或高脂饮食（HFD）12周。与WT对照组相比，喂食HFD的Adar 1 +/−小鼠表现出脂肪量减少的瘦型，尽管在食物饮食条件下没有发现差异。血生化分析和胰岛素耐量试验表明Adar 1 +/−可改善HFD引起的血脂异常和胰岛素抵抗。代谢研究表明，在HFD条件下，与WT小鼠相比，Adar 1 +/−小鼠的食物摄入量减少。配对喂养研究进一步表明，Adar 1 +/−通过减少食物摄入来保护小鼠免受HFD诱导的肥胖。此外，Adar 1 +/−恢复了HFD条件下胃中增加的ghrelin表达和降低的血清肽YY水平。这些数据表明，ADAR 1可能有助于饮食诱导的肥胖，至少部分地，通过调节生长激素释放肽和肽YY的表达和secretory.NEW & NOTEWORTHThis研究确定腺苷脱氨酶作用于RNA 1作为一种新的因素，促进高脂饮食诱导的肥胖，至少部分地，通过调节食欲相关基因生长激素释放肽和PYY。
Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases, and many other chronic diseases. The objective of this study was to determine the role of adenosine deaminase acting on RNA 1 (ADAR1) in the development of obesity and insulin resistance. Wild-type (WT) and heterozygous ADAR1-deficient (Adar1+/−) mice were fed normal chow or a high-fat diet (HFD) for 12 wk.Adar1+/−mice fed with HFD exhibited a lean phenotype with reduced fat mass compared with WT controls, although no difference was found under chow diet conditions. Blood biochemical analysis and insulin tolerance test showed thatAdar1+/−improved HFD-induced dyslipidemia and insulin resistance. Metabolic studies showed that food intake was decreased inAdar1+/−mice compared with the WT mice under HFD conditions. Paired feeding studies further demonstrated thatAdar1+/−protected mice from HFD-induced obesity through decreased food intake. Furthermore,Adar1+/−restored the increased ghrelin expression in the stomach and the decreased serum peptide YY levels under HFD conditions. These data indicate that ADAR1 may contribute to diet-induced obesity, at least partially, through modulating the ghrelin and peptide YY expression and secretion.NEW & NOTEWORTHYThis study identifies adenosine deaminase acting on RNA 1 as a novel factor promoting high-fat diet-induced obesity, at least partially, through modulating appetite-related genes ghrelin and PYY.