Yu Siriguleng, Liu Chaoqun, Lv Hong, Guo Zhijun, Yao Hongqiang, Wen Xin, Xiu Ying, Gao Wa, Li Ziyi, Yu Wen, Niu Yaru, Jin Junjian
College of Veterinary Medicine, Inner Mongolia Agricultural University, Huhhot, China.
Key Laboratory of Clinical Diagnosis and Treatment Technology for Animal Diseases, Ministry of Agriculture, Hohhot, China.
Front Vet Sci. 2025 Aug 14;12:1477593. doi: 10.3389/fvets.2025.1477593. eCollection 2025.
MiR-144-5p is differentially expressed in plasma exosomes from Bactrian camels of varying body sizes, with GO and KEGG analyses indicating that its target genes play crucial roles in lipid metabolism. PGC-1α, confirmed as a key target through RNA pull-down and dual-luciferase reporter assays, is a significant regulator of this process. This study aims to investigate the impact of miR-144-5p on lipid metabolism in a mouse model of high-fat diet (HFD)-induced obesity to elucidate the mechanistic pathways involved.
Male C57BL/6 mice were assigned to groups and fed either a control diet or an HFD for 12 weeks, which was followed by a 3-week intervention with miR-144-5p. Various metabolic parameters and gene expressions were evaluated to determine the effects of this treatment.
The treatment significantly reduced diet-induced adiposity and decreased inflammatory responses. Additionally, it inhibited PGC-1α expression in the liver tissue of HFD-fed mice. There was an increase in CPT1 activity and fatty acid β-oxidation rate, along with the downregulation of FASN mRNA expression and the upregulation of CPT1 and ACOX1 expression, promoting fatty acid oxidation.
These findings suggest that miR-144-5p exerts anti-obesity effects by enhancing fatty acid oxidation, likely through modulation of the PGC-1α/AMPK signaling pathway. This study provides new insights into potential miRNA-based therapeutic strategies for obesity and related metabolic disorders.
miR-144-5p在不同体型双峰驼的血浆外泌体中差异表达，基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明其靶基因在脂质代谢中起关键作用。通过RNA下拉和双荧光素酶报告基因检测确定为关键靶标的过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）是这一过程的重要调节因子。本研究旨在探讨miR-144-5p对高脂饮食（HFD）诱导肥胖小鼠模型脂质代谢的影响，以阐明其中涉及的机制途径。
将雄性C57BL/6小鼠分组，分别给予对照饮食或高脂饮食12周，随后用miR-144-5p进行3周干预。评估各种代谢参数和基因表达以确定该治疗的效果。
该治疗显著降低了饮食诱导的肥胖并减轻了炎症反应。此外，它抑制了高脂饮食喂养小鼠肝脏组织中PGC-1α的表达。肉碱棕榈酰转移酶1（CPT1）活性和脂肪酸β-氧化率增加，同时脂肪酸合酶（FASN）mRNA表达下调，CPT1和酰基辅酶A氧化酶1（ACOX1）表达上调，促进了脂肪酸氧化。
这些发现表明，miR-144-5p可能通过调节PGC-1α/腺苷酸活化蛋白激酶（AMPK）信号通路增强脂肪酸氧化，从而发挥抗肥胖作用。本研究为基于微小RNA（miRNA）的肥胖及相关代谢紊乱治疗策略提供了新的见解。
