Producción CyT

Medicina - The pan TGF-B inhibitor BRECEPT encoded by a lentiviral vector ameliorates metabolic syndrome in a murine model

Congreso

Autoría:

Cámara CA. ; La Colla A. ; Rodriguez TM. ; Echarte SM. ; Dewey RA. ; Chisari AN.

Fecha:

2022

Editorial y Lugar de Edición:

Medicina

Resumen *

Metabolic syndrome (MS) is a growing public health problem close- ly related to insulin resistance (IR) and obesity and is also associ- ated with an increased risk of developing non-alcoholic fatty liver disease, cardiovascular diseases, and type II diabetes. Nowadays, treatments for MS patients are limited. Molecular signals between the liver and adipose tissue could regulate lipid storage in adipose tissue. The TGF-β pathway is linked to hepatic steatosis and liver fibrosis. Brecept (Br), a pan TGF-β inhibitor, was developed by fus- ing TβRII-SE, a novel soluble TGF-β type II receptor splice variant, to the Fc portion of human IgG (TβRII-SE/Fc). We aimed to study the effect of lentiviral-mediated liver overexpression of Br (Lv-Br) in a rat model of MS induced by Western Diet (WD). We compared three groups: control diet, WD, and WD+Lv-Br that received an in- trahepatic injection of the lentiviral vector encoding Br at week 10. At week 18, we observed lower glycemia (p<0.05) and IR (p<0.01) in the Lv-Br group than in the WD group by insulin tolerance test. In week 21, animals were sacrificed. In liver tissue stained with H&E and Masson’s Trichome, we observed in the WD+Lv-Br group, com- pared with the WD group, a remarkably decreased microvesicular steatosis and inflammatory infiltrate in the portal triad (PT). Further- more, we found that fibrosis in the central vein (CV) and PT was significantly reduced (p<0.001). In adipose tissue stained with H&E, we observed hyperplasia (p<0.01) and a tendency to atrophy in adi- pocytes, comparing the WD+Lv-Br group with the WD group. Finally, in transmission electron microscopy liver sections, we observed an important decrease in lipid droplet number/field (p<0.001), mean lip- id droplet area/field (p<0.001), endoplasmic reticulum hypertrophy, and lower swollen mitochondria in the WD+Lv-Br group than in the WD group. Therefore, these results suggest that liver overexpres- sion of Br exerts a beneficial effect against MS induced by a WD in rats. Información suministrada por el agente en SIGEVA

Palabras Clave

metabolic syndromeliverBRECEPTTGFb