HEMIN IMPROVES LIPID METABOLISM IN A RAT MODEL OF NON-ALCOHOLIC FATTY LIVER DISEASE

SCHIAPPACASSE A; CALDARERI L; REPETTO EM; WISZNIEWSKI M; CYMERYNG CB

Congreso; Reunión Anual de Biociencias 2021; 2021

The liver plays a major role in controlling systemic lipid metabolism and an imbalance between lipids intake and secretion can lead to insulin resistance and Non-Alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disorder that is associated with cardiovascular disease. Previous results from our laboratory showed an increase in serum triglyceride (TAG) levels in rats fed a sucrose rich diet (SRD) for 12 weeks. The administration of hemin (15mg/kg ip, every 48hs) during the last two weeks of SRD reduced TAG levels, while no changes were detected in systemic insulin resistance and hepatic triglyceride levels. Based on these results the aim of the present study was to analyze the effects of hemin on hepatic lipid metabolism. Male Wistar rats were randomly distributed into control (C) and SRD groups (30% sucrose in the drinking water). Hemin was administered as described (SRD+H). Livers were harvested and total RNA and proteins were extracted. Our results showed an increased gene expression of the transcription factor ChREBP, and the lipid synthesis enzymes FAS and ACC1 (0,001 vs. C group), as well as FAS protein expression (0,001 vs. C) in SRD treated rats. Although hemin administration had no effect on the gene expression of ChREBP or ACC1, it caused a significant increase in SREBP1c, FAS, and DGAT1/2 levels (0,05 vs. SRD or C). Interestingly, when we analyze the genes involved in the liver capacity to oxidize lipids we found that SRD+H treated animals showed an increase in the gene expression of PPAR𝛂, CPT1𝛂 and ACOX1𝛂 (0,01, 0,05, and 0.001 vs. SRD respectively). Furthermore, protein levels of p-AMPK and nuclear protein levels of PPAR𝛂 were also increased (0,05 and 0,01 vs. C and SRD, respectively). In summary our results led us to hypothesize that hemin administration associated with a reduction of triglyceridemia is due to an increase in the oxidation of lipids within the liver, possibly through the stimulation of the AMPK/PPAR𝛂 pathway.