The pan TGF-beta inhibitor Brecept encoded by a lentiviral vector ameliorates metabolic syndrome in a murine model

CAROLINA CÁMARA; ANABELA LA COLLA; TANIA MELINA RODRÍGUEZ; STELLA MARIS ECHARTE; RICARDO A. DEWEY; ANDREA NANCY CHISARI

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias 2022 (SAIC-SAI-SAFIS); 2022

SAIC-SAI-SAFIS

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 fusing 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) ina 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