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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

Received: 　　Accepted:

Corresponding author: 姚柳　　E-mail:

DOI: 10.13294/j.aps.2025.0039

Citing This Article：

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).