HEME OXYGENASE 1 INDUCTION ALLEVIATES HEPATIC INSULIN RESISTANCE IN MALE WISTAR RATS

WISZNIEWSKI, MORENA; REPETTO, ESTEBAN M.; PEZZANITI A; CYMERYNG, CORA

VIRTUAL

Congreso; INTERNATIONAL CONGRESS OF ENDOCRINOLOGY ICE2021; 2021

INTERNATIONAL SOCIETY FOR ENDOCRINOLOGY

Introduction: As the pandemic of obesity spreads, non-alcoholic fatty liver disease (NAFLD) has become one of the mostprevalent liver diseases worldwide both in adults and children. NAFLD is the hepatic component of the metabolicsyndrome and therefore is associated with the development of type 2 diabetes and cardiovascular disease. In ourlaboratory we focus on the heme oxygenase-1 (HO-1) system as a possible therapeutic target based on its antioxidantand cytoprotective activities.Objectives: The main goal of the present study was to evaluate the effects of HO-1 induction in systemic and hepaticparameters of insulin resistance in an animal model of the disease generated by the administration of a sucrose rich diet(SRD).Methods: Male Wistar rats were randomly distributed into control (C) and SRD groups (30% sucrose in the drinkingwater, for 12 weeks). Hemin treatment was administered for the last 2 weeks (15mg/kg/ip every 48hs, H and SRD+Hgroups).Results: At the end of the treatments, liver HO-1 induction was confirmed after hemin administration via western blot.Animals of the SRD group presented hypertriglyceridemia (p<0.001 vs. C), an effect that was significantly attenuated byhemin treatment (p<0.001 vs. SRD, p<0.05 vs. C). SRD treated rats showed lower insulin sensitivity than controls, asassessed by an insulin tolerance test (KITT, p<0.0001 vs. C) but KITT was not affected by hemin treatment. Results from apyruvate tolerance test, performed to determine hepatic insulin resistance showed an increased glucose output in SRDtreated animals (p<0.05 vs. C). In agreement, protein levels of PEPCK, a gluconeogenic enzyme, were also increased inthis group (p<0.05 vs. C). Insulin induced AKT phosphorylation (1IU/kg ip) was significantly decreased in the SRD group(p<0.001 vs. C). Hemin treatment corrected all these parameters (p<0.05 vs. SRD). Both mRNA and protein levels ofPPARalpha were increased in the SRD+H group (p<0.001 vs. C and p<0.05 vs. SRD).Conclusion: In summary, hemin treatment of IR-rats is associated with an improvement in insulin sensitivity in the liver,and a greater oxidation of fatty acids, while no changes in systemic insulin resistance were detected.