Alenezi Rashid Fahed, Abdelkhalek Adel, El-Sayed Gehad, Pet Ioan, Ahmadi Mirela, Sherbini El Said El, Pușcașiu Daniela, Arisha Ahmed Hamed
Biochemistry and Molecular Biology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
Department of Food Safety, Hygiene and Technology, Faculty of Veterinary Medicine, Badr University in Cairo, Badr City 11829, Egypt.
Biomolecules. 2025 Jul 27;15(8):1086. doi: 10.3390/biom15081086.
Chronic high-fat diet (HFD) feeding in male rats causes significant metabolic as well as inflammatory disturbances, including obesity, insulin resistance, dyslipidemia, liver and kidney dysfunction, oxidative stress, and hypothalamic dysregulation. This study assessed the therapeutic effects of chlorogenic acid (CGA), a natural polyphenol, administered at 10 mg and 100 mg/kg/day for the last 4 weeks of a 12-week HFD protocol. Both CGA doses reduced body weight gain, abdominal circumference, and visceral fat accumulation, with the higher dose showing greater efficacy. CGA improved metabolic parameters by lowering fasting glucose and insulin and enhancing lipid profiles. CGA suppressed orexigenic genes (Agrp, NPY) and upregulated anorexigenic genes (POMC, CARTPT), suggesting appetite regulation in the hypothalamus. In abdominal white adipose tissue (WAT), CGA boosted antioxidant defenses (SOD, CAT, GPx, HO-1), reduced lipid peroxidation (MDA), and suppressed pro-inflammatory cytokines including TNF-α, IFN-γ, and IL-1β, while increasing the anti-inflammatory cytokine IL-10. CGA modulated inflammatory signaling via upregulation of miR-146a and inhibition of IRAK1, TRAF6, and NF-κB. It also reduced apoptosis by downregulating p53, Bax, and Caspase-3, and restoring Bcl-2. These findings demonstrate that short-term CGA administration effectively reverses multiple HFD-induced impairments, highlighting its potential as an effective therapeutic for obesity-related metabolic disorders.
雄性大鼠长期高脂饮食（HFD）会导致显著的代谢和炎症紊乱，包括肥胖、胰岛素抵抗、血脂异常、肝肾功能障碍、氧化应激和下丘脑调节异常。本研究评估了绿原酸（CGA），一种天然多酚，在为期12周的HFD方案的最后4周以10毫克/千克/天和100毫克/千克/天的剂量给药的治疗效果。两种CGA剂量均降低了体重增加、腹围和内脏脂肪堆积，较高剂量显示出更大的疗效。CGA通过降低空腹血糖和胰岛素水平以及改善血脂状况来改善代谢参数。CGA抑制了促食欲基因（Agrp、NPY）并上调了抑食欲基因（POMC、CARTPT），表明其对下丘脑食欲的调节作用。在腹部白色脂肪组织（WAT）中，CGA增强了抗氧化防御（SOD、CAT、GPx、HO-1），减少了脂质过氧化（MDA），并抑制了包括TNF-α、IFN-γ和IL-1β在内的促炎细胞因子，同时增加了抗炎细胞因子IL-10。CGA通过上调miR-146a和抑制IRAK1、TRAF6和NF-κB来调节炎症信号。它还通过下调p53、Bax和Caspase-3并恢复Bcl-2来减少细胞凋亡。这些发现表明，短期给予CGA可有效逆转多种HFD诱导的损伤，突出了其作为肥胖相关代谢紊乱有效治疗方法的潜力。
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