Zidovudine ameliorates metabolic disorders in HFD-fed rats by enhancing fatty acid oxidation
10.11665/j.issn.1000-5048.2025102401
- VernacularTitle:齐多夫定通过促进脂肪酸氧化改善高脂饮食诱导的大鼠代谢紊乱
- Author:
Jing ZHANG
1
;
Ziai JIN
;
Ziyue WANG
;
Junqian LIN
;
Tao WANG
Author Information
1. 中国药科大学多靶标天然药物全国重点实验室新药筛选中心, 南京 210009;江苏省药效研究与评价服务中心, 南京 210009
- Publication Type:Journal Article 期刊文章
- Keywords:
zidovudine;
high-fat diet;
metabolic disorder;
fatty acid oxidation;
oxidative stress;
mitochondrial function;
PPAR signaling pathway
- From:
Journal of China Pharmaceutical University
2026;57(2):256-265
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to investigate the effects of zidovudine (AZT) on high-fat diet (HFD)-induced metabolic disturbances in rats and its underlying mechanisms. The HFD rat model was established, and the animals were divided into the control group, the model group, and the AZT-treated group at low (25 mg/kg) and high (50 mg/kg) doses. Metabolic phenotype, hepatic lipid deposition, oxidative stress, mitochondrial function, and peroxisome proliferator-activated receptor (PPAR) signaling were evaluated. AZT treatment significantly mitigated HFD-induced body weight gain and reduced both the mass and adipocyte size of inguinal and epididymal white adipose tissues; it also enhanced metabolic flexibility and improved glucose tolerance without elevating blood lactate levels. High-dose AZT further lowered hepatic triglyceride accumulation, ameliorated steatosis, and additionally, attenuated hepatic oxidative stress by increasing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) levels. Western blot analysis revealed that AZT upregulated hepatic PPARα and carnitine palmitoyltransferase 1α (CPT1α), while downregulating PPARγ expression. In conclusion, AZT effectively ameliorates HFD-induced metabolic disorders without inducing mitochondrial toxicity, which may be related to the promotion of fatty acid oxidation, the reduction of oxidative stress, and the modulation of both the PPAR signaling pathway and pyrimidine metabolism.
