Role of miR-144-5p in Modulating Lipid Metabolism and Potentially Alleviating Obesity via the PGC-1α/AMPK Pathway

Siriguleng YU^1*Xin Wen¹Ying Xiu²Wa Gao³Ziyi Li¹Wen Yu¹Yaru Niu¹Junjian Jin¹

• ¹College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, China
• ²Department of Public Health, Inner Mongolia Center for Disease Control and Prevention, Hohhot, China
• ³Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot, Inner Mongolia Autonomous Region, China

MiR-144-5p is differentially expressed in plasma exosomes from Bactrian camels of varying body sizes. GO and KEGG analyses have shown that the target genes of miR-144-5p play a crucial role in lipid metabolism. PGC-1α has been identified as a key target, which was confirmed using RNA pulldown assays and dual-luciferase reporter assays. Building on these findings, this study investigated the impact of miR-144-5p on lipid metabolism in mice with obesity induced by a high-fat diet (HFD) to better understand the mechanistic pathways. Male C57BL/6 mice were divided into groups and fed either a control diet or an HFD for 12 weeks, followed by a 3-week miR-144-5p intervention. Treatment with miR-144-5p significantly reduced diet-induced adiposity, decreased inflammatory responses, and inhibited PGC-1α expression in the liver tissue of HFD-fed mice. Additionally, the intervention increased CPT1 activity and the fatty acid β-oxidation rate. The intervention also led to a notable downregulation of FASN mRNA expression, while upregulating 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.