Tu219 - ACE2 Expression in the Liver of Obese People Is Associated with Anthropometric, Biochemical, and Proinflammatory Cytokine Variables

José Alfonso Arreola Miranda; Galileo Escobedo; Nydia angélica Ocampo Aguilar; Itzel Pérez Baltazar; José Ángel Sotelo Hernández; Lucía Angélica Méndez García

Abstract Text: Obesity is characterized by chronic low-grade inflammation associated with developing and progressing metabolic dysfunction-associated fatty liver disease (MAFLD). The pathogenesis of MAFLD depends on multiple factors, such as the disruption of the renin-angiotensin system (RAS) balance. There is evidence that increased activation of the hepatic classical RAS axis or inhibition of the alternative axis is associated with increased expression of lipid oxidation, oxidative stress, and inflammation genes. Moreover, it has been proposed that obesity can trigger a loss of balance in this system. To understand in greater depth the characteristics of the hepatic RAS in obesity, this work aimed to determine in liver samples from patients with obesity the association of ACE2 with cytokine protein levels, as well as with different biochemical, clinical, and anthropometric parameters. Thus, seventy liver tissue samples from patients with obesity were included. To assess the expression of ACE2 and proinflammatory cytokines, RT-qPCR was performed. The concentration of cytokines was evaluated using an immunoassay with magnetic beads. We found that the expression of ACE2 is higher in men than in women, in people with comorbidities vs. without comorbidities, and in subjects with systemic arterial hypertension (SAH) vs. no HAS. Likewise, an inverse correlation was found between the expression levels of ACE2 and the serum concentration of GGT. Finally, we found that TNF-α positively influences ACE2 mRNA levels. Based on these results, it is likely that with increasing TNF-α, the susceptibility to develop MAFLD increases, and as TNF-α levels in the liver increase and consequently, ACE2.