RT Journal Article
T1 A synergic GLP-1/Acylethanolamide-based combined therapy for MAFLD: Studies in rat models
A1 De Ceglia, Marialuisa
A1 Tovar, Rubén
A1 Rodríguez-Pozo, Miguel
A1 Vargas, Antonio
A1 Gavito, Ana L.
A1 Suárez-Pérez, Juan
A1 Baixeras-Llano, Elena
A1 Rodriguez de Fonseca, Fernando
A1 Decara, Juan
K1 Obesidad
K1 Receptores de hormonas
K1 Metabolismo
K1 Hígado -- Enfermedades
AB Obesity remains a major epidemic in developed countries, with metabolic-associated fatty liver disease (MAFLD)as one of its main hepatic consequences. Pharmacological treatments for MAFLD are limited, but modulation ofglucagon-like peptide-1 (GLP-1) or acylethanolamide signalling offers promising therapeutic potential, whileexerting anti-obesity effects. This study evaluated the effects of a combined therapy using a dual ligand targetingperoxisome proliferator-activated receptor alpha (PPARα) and peripheral cannabinoid receptor 1 (CB1) (OLHHA,acting as a PPARα agonist and CB1 antagonist) in combination with the GLP-1 receptor agonist liraglutide. Ouraim was to assess their potential as a multitarget therapy to ameliorate liver dysfunction in an obesity animalmodel. In Wistar rats, we evaluated the effects of administering 3 mg/kg OLHHA and 25 µg/kg liraglutide, bothacutely and chronically (daily for 42 days), in the context of exposure to a high-fat/high-fructose diet. Althoughboth OLHHA and liraglutide individually ameliorated certain hepatic alterations induced by MAFLD, our findingsdemonstrate that their combined administration was significantly more effective in promoting body weight loss,improving lipid profiles and transaminase levels, and exerting robust antisteatotic effects in obese rats. Thisenhanced efficacy was evidenced by a marked reduction in hepatic fat content, downregulation of lipogenesisrelated enzymes, and upregulation of proteins involved in lipid oxidation. Moreover, OLHHA, either alone orin combination with liraglutide, efficiently restored redox balance disrupted by MAFLD in obese rats.
PB Elsevier
YR 2025
FD 2025
LK https://hdl.handle.net/10630/40477
UL https://hdl.handle.net/10630/40477
LA eng
NO Ceglia M, Tovar R, Rodríguez-Pozo M, Vargas A, Gavito A, Suárez J, Baixeras E, Rodríguez de Fonseca F, Decara J. A synergic GLP-1/Acylethanolamide-based combined therapy for MAFLD: Studies in rat models. Biochemical Pharmacology. 2025;242(3):117364. https://doi.org/10.1016/j.bcp.2025.117364
NO Funding for open access charge: Universidad de Málaga/CBUA
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 4 mar 2026