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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
A Natural Polyphenol, Chlorogenic Acid, Attenuates Obesity-Related Metabolic Disorders in Male Rats via miR-146a-IRAK1-TRAF6 and NRF2-Mediated Antioxidant Pathways
Author
Alenezi, Rashid Fahed 1 ; Abdelkhalek Adel 2 ; El-Sayed, Gehad 1 ; Pet Ioan 3   VIAFID ORCID Logo  ; Ahmadi Mirela 3   VIAFID ORCID Logo  ; Sherbini El Said El 1 ; Pușcașiu Daniela 4 ; Arisha Ahmed Hamed 5   VIAFID ORCID Logo 

 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 
 Department of Biotechnology, Faculty of Bioengineering of Animals Resources, University of Life Sciences “King Mihai I” from Timisoara, 300645 Timisoara, Romania, Institute of Applied Biotechnology, 300645 Timisoara, Romania 
 Faculty of Medicine, Victor Babes University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Street, 300041 Timisoara, Romania, ANAPATMOL Research Center, Victor Babes University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Street, 300041 Timisoara, Romania 
 Department of Animal Physiology and Biochemistry, Faculty of Veterinary Medicine, Badr University in Cairo, Badr City 11829, Egypt, Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt 
First page
1086
Publication year
2025
Publication date
2025
Publisher
MDPI AG
e-ISSN
2218273X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3243987493
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.