Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan.
J Biochem. 2022 Jan 7;171(1):63-73. doi: 10.1093/jb/mvab106.
Brown and beige adipocytes, which express thermogenic uncoupling protein-1 (UCP1), stimulate glucose and lipid metabolism, improving obesity and metabolic diseases such as type 2 diabetes and hyperlipidemia. Overexpression of cellular repressor of E1A-stimulated genes 1 (CREG1) promotes adipose tissue browning and inhibits diet-induced obesity (DIO) in mice. In this study, we investigated the effects of CREG1 administration on DIO inhibition and adipose browning. Subcutaneous administration of recombinant CREG1 protein to C57BL/6 mice stimulated UCP1 expression in interscapular brown adipose tissue (IBAT) and improved DIO, glucose tolerance and fatty liver compared with those in phosphate-buffered saline-treated mice. Injection of Creg1-expressing adenovirus into inguinal white adipose tissue (IWAT) significantly increased browning and mRNA expression of beige adipocyte marker genes compared with that in mice injected with control virus. The effect of Creg1 induction on beige adipocyte differentiation was supported in primary culture using preadipocytes isolated from IWAT of Creg1-transgenic mice compared with that of wild-type mice. Our results indicate a therapeutic effect of CREG1 on obesity and its associated pathology and a potential of CREG1 to stimulate brown/beige adipocyte formation.
棕色和米色脂肪细胞表达解偶联蛋白 1（UCP1），可刺激葡萄糖和脂质代谢，改善肥胖和代谢疾病，如 2 型糖尿病和高脂血症。细胞 E1A 刺激基因 1 的抑制剂（CREG1）的过表达可促进脂肪组织褐变，并抑制小鼠的饮食诱导肥胖（DIO）。在这项研究中，我们研究了 CREG1 给药对 DIO 抑制和脂肪褐变的影响。重组 CREG1 蛋白的皮下给药可刺激 C57BL/6 小鼠肩胛间棕色脂肪组织（IBAT）中 UCP1 的表达，并改善 DIO、葡萄糖耐量和脂肪肝，与磷酸盐缓冲盐水处理的小鼠相比。与注射对照病毒的小鼠相比，将表达 Creg1 的腺病毒注入腹股沟白色脂肪组织（IWAT）可显著增加褐色脂肪细胞标记基因的褐变和 mRNA 表达。与野生型小鼠相比，用 Creg1 转基因小鼠 IWAT 分离的前体脂肪细胞进行的原代培养支持 Creg1 诱导对米色脂肪细胞分化的作用。我们的结果表明 CREG1 对肥胖及其相关病理具有治疗作用，并且 CREG1 具有刺激棕色/米色脂肪细胞形成的潜力。
