CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Hemin improves lipid metabolism in a rat model of non - alcoholic fatty liver disease
Autor/es:
ESTEBAN M. REPETTO; MARTINEZ CALEJMAN, C; WISZNIEWSKI, M; CORA B. CYMERYNG; MORI D
Lugar:
VIRTUAL
Reunión:
Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2021; 2021
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
Currently, metabolic dysfunction associated with fatty liver affects aquarter of the world population, but no pharmacological treatmenthas been recommended yet. We have previously shown that de-pletion of Kupffer cells (KC) in rats fed a sucrose-rich diet (SRD) for12 weeks attenuates tissue injury and prevents liver inflammation,without changing the degree of steatosis. The aim of this study wasto evaluate the effects of hemin treatment (an HO-1 inducer) on liverdamage induced by SRD and identify the underlying mechanisms.SRD-treated rats are presented with IR, hepatic steatosis, and highserum levels of NEFAS, glycemia, and triacylglycerides (TAG). Ad-ministration of hemin for the last two weeks of the dietary intervention (15 mg/kg/48h, SRD+H) did not modify these parameters, except for the observed reduction in serum TAG levels. A lower degree of ballooning (histological change compatible 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-treated rats. The induction of HO-1 expression in KC by hemin was associated with lower tissue levels of IL1b, TNFa and pP65 compared to the SRD group. Induction of PEPCK as well as the response to pyruvate were blocked by hemin, that also restored the ratio pAkt/Akt altered by SRD. Finally, animals in the SRD+H group showed an increase in the expression of PPARa, CPT1a and ACOX1a (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 associated with the induction of HO-1. Moreover, hemin treatment is also able to decrease TAG serum levels by increasing lipid oxidation through the stimulation of the AMPK/PPARa pathway in the liver.