INVESTIGADORES
MARTINEZ CALEJMAN Camila
congresos y reuniones científicas
Título:
HO-1 AS A THERAPEUTIC TARGET IN A RAT MODEL OF MAFLD: KEY ROLE OF KUPFFER CELLS
Autor/es:
ESTEBAN MARTIN REPETTO; WISZNIEWSKI, MORENA; MORI, DIEGO ; MARTINEZ CALEJMAN C; CYMERYNG C. B.
Lugar:
Mar del Plata
Reunión:
Congreso; Reunion Anual de sociedades de Biociencias; 2021
Institución organizadora:
Sociedad Argentina de Investigaciones Clinicas
Resumen:
Currently, metabolic dysfunction associated with fatty liver affects a quarter of the worldpopulation, but no pharmacological treatment has been recommended yet. We havepreviously shown that depletion of Kupffer cells (KC) in rats fed a sucrose-rich diet (SRD) for 12weeks attenuates tissue injury and prevents liver inflammation, without changing the degreeof steatosis. The aim of this study was to evaluate the effects of hemin treatment (an HO-1inducer) on liver damage induced by SRD and identify the underlying mechanisms.SRD-treated rats are presented with IR, hepatic steatosis, and high serum levels of NEFAS,glycemia, and triacylglycerides (TAG). Administration of hemin for the last two weeks of thedietary intervention (15 mg/kg/48h, SRD+H) did not modify these parameters, except for theobserved reduction in serum TAG levels. A lower degree of ballooning (histological changecompatible with injury) as well as a decrease in oxidative stress parameters (TBARS and 3-nitrotyrosine levels, SOD and catalase activities), UPR (expression of XBP1s, ATF4 and GRP78)and apoptosis (TUNEL and cleaved caspase-3 expression) were also detected in SRD-treatedrats. The induction of HO-1 expression in KC by hemin was associated with lower tissue levelsof IL1, TNF and pP65 compared to the SRD group. Induction of PEPCK as well as theresponse to pyruvate were blocked by hemin, that also restored the ratio pAkt/Akt altered bySRD. Finally, animals in the SRD+H group showed an increase in the expression of PPAR,CPT1 and ACOX1 (proteins involved in lipid oxidation), and an increase in pAMPK (vs. SRD).In summary, our results lead us to hypothesize that administration of hemin attenuates liverinjury induced by sucrose diet by reducing the pro-inflammatory tone of the KC associatedwith the induction of HO-1. Moreover, hemin treatment is also able to decrease TAG serumlevels by increasing lipid oxidation through the stimulation of the AMPK/PPAR pathway in theliver.