CREG1 improves diet‐induced obesity via uncoupling protein 1‐dependent manner in mice
CREG1 improves diet‐induced obesity via uncoupling protein 1‐dependent manner in mice
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DOI：
10.1111/gtc.12920
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发表时间：
2022-01
期刊：
影响因子：
2.1
通讯作者：
Yuki Endo;M. Hashimoto;Tatsuya Kusudo;T. Okada;T. Takeuchi;Ayumi Goto;H. Yamashita
中科院分区：
文献类型：
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作者：
Yuki Endo;M. Hashimoto;Tatsuya Kusudo;T. Okada;T. Takeuchi;Ayumi Goto;H. Yamashita
产热棕色和米色脂肪细胞表达解偶联蛋白1（UCP 1）并刺激能量代谢，预防肥胖和2型糖尿病和高脂血症等代谢疾病。E1 A刺激基因1（CREG 1）的细胞阻遏物可以刺激产热脂肪形成，诱导UCP 1，并在正常室温下减少小鼠的饮食诱导肥胖（DIO）。在这项研究中，我们研究了CREG 1给药的效果和UCP 1在30°C热中性条件下抑制DIO的重要性，这减弱了产热脂肪的形成。有趣的是，与PBS处理的小鼠相比，通过渗透泵在C57 BL/6 J小鼠中皮下给予重组CREG 1蛋白4周增加了肩胛间棕色脂肪组织（IBAT）中的UCP 1表达，抑制了内脏白色脂肪肥大伴部分布朗宁，并减少了DIO。与PBS处理的小鼠相比，CREG 1处理的小鼠的IBAT中能量代谢相关基因的mRNA表达显著增加。相比之下，CREG 1的脂肪细胞特异性过表达未能改善热中性下UCP 1敲除小鼠的DIO。我们的研究结果表明，在产热脂肪衰减条件下CREG 1给药对肥胖的治疗潜力，并强调了UCP 1在CREG 1的DIO抑制作用中不可或缺的作用。
Thermogenic brown and beige adipocytes express uncoupling protein 1 (UCP1) and stimulate energy metabolism, protecting against obesity and metabolic diseases such as type 2 diabetes and hyperlipidemia. Cellular repressor of E1A‐stimulated genes 1 (CREG1) can stimulate thermogenic fat formation, induce UCP1, and reduce diet‐induced obesity (DIO) in mice at normal room temperature. In this study, we investigated the effect of CREG1 administration and the importance of UCP1 in DIO inhibition under thermoneutral conditions at 30°C, which attenuate thermogenic fat formation. Interestingly, subcutaneous administration of recombinant CREG1 protein via an osmotic pump in C57BL/6J mice for four weeks increased UCP1 expression in interscapular brown adipose tissue (IBAT), inhibited visceral white fat hypertrophy with partial browning, and reduced DIO compared to that in PBS‐treated mice. The mRNA expression of energy metabolism‐related genes was significantly increased in the IBAT of CREG1‐treated mice compared to that in PBS‐treated mice. In contrast, adipocyte‐specific overexpression of CREG1 failed to improve DIO in UCP1‐knockout mice at thermoneutrality. Our results indicate the therapeutic potential of CREG1 administration for obesity under thermogenic fat‐attenuating conditions and highlight the indispensable role of UCP1 in the DIO‐inhibitory effect of CREG1.