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皮下白色脂肪组织局部过表达miR-429海绵改善肥胖及相关代谢紊乱

姚柳^1,*, 修雯靖¹, 叶晨吉², 贾新宇¹, 董雯蕙¹, 王春炅¹

¹天津医科大学生理学与病理生理学系，天津 300070；²新乡医学院，河南省医用组织再生重点实验室，新乡 453000

摘要

肥胖是世界范围内严重的健康问题。能量代谢失衡是肥胖以及相关能量代谢性疾病发生的重要原因。我们前期研究发现抑制miR-429可增加米色脂肪细胞解偶联蛋白-1的表达，但皮下白色脂肪组织局部抑制miR-429是否影响饮食导致的肥胖及相关代谢紊乱尚不清楚。本研究旨在探讨皮下白色脂肪组织局部过表达miR-429海绵(sponge)对肥胖及相关代谢紊乱的影响。分别给予C57BL/6小鼠双侧腹股沟脂肪垫定点注射对照腺相关病毒和表达miR-429海绵的腺相关病毒，1周后，高脂饮食喂养10周构建肥胖动物模型，检测小鼠体重、脂肪重、血糖、血脂以及肝脏脂质的变化。结果显示，与对照组相比，皮下白色脂肪组织过表达miR-429海绵减轻了小鼠体重和脂肪重量，改善空腹血糖水平以及葡萄糖耐量，降低血浆胆固醇水平，并且缓解肝脏脂质沉积。机制探究发现抑制miR-429可显著上调脂肪细胞和脂肪组织中解偶联蛋白-1的表达。以上结果表明，局部抑制皮下白色脂肪组织中的miR-429可能通过上调解偶联蛋白-1的表达改善肥胖及相关代谢紊乱，miR-429是肥胖及相关代谢紊乱的潜在治疗靶点。

关键词： 高脂饮食; miR-429; 皮下白色脂肪组织; 肥胖; 脂代谢

Local overexpression of miR-429 sponge in subcutaneous white adipose tissue improves obesity and related metabolic disorders

YAO Liu^1,*, XIU Wen-Jing¹, YE Chen-Ji², JIA Xin-Yu¹, DONG Wen-Hui¹, WANG Chun-Jiong¹

¹Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China；²Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453000, China

Abstract

Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.

Key words: high-fat diet; miR-429; subcutaneous white adipose tissue; obesity; lipid metabolism

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通讯作者：姚柳　　E-mail:

DOI: 10.13294/j.aps.2025.0039

引用本文：

姚柳, 修雯靖, 叶晨吉, 贾新宇, 董雯蕙, 王春炅. 皮下白色脂肪组织局部过表达miR-429海绵改善肥胖及相关代谢紊乱[J]. 生理学报 2025; 77 (3): 441-448.

YAO Liu, XIU Wen-Jing, YE Chen-Ji, JIA Xin-Yu, DONG Wen-Hui, WANG Chun-Jiong. Local overexpression of miR-429 sponge in subcutaneous white adipose tissue improves obesity and related metabolic disorders. Acta Physiol Sin 2025; 77 (3): 441-448 (in Chinese with English abstract).