Liver overexpression of the novel pan-TGF-β inhibitor Brecept ameliorates lipid metabolism disorders in a MAFLD rat model

TANIA MELINA RODRÍGUEZ; VICTORIA GONZÁLEZ SCARVAGLIERI ; ANABEL LA COLLA; CAROLINA SENDÓN; ANDREA NANCY CHISARI; CAROLINA CÁMARA; STELLA MARIS ECHARTE; RICARDO A. DEWEY

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias 2023; 2023

Metabolic-associated fatty liver disease (MAFLD) is characterized by the pathological accumulation of triglycerides in hepatocytes, obesity, and metabolic dysfunction. Treatments for MAFLD patients are limited. The TGF-β pathway modulates lipid metabolism in hepatocytes. Brecept (Br), a pan TGF-β inhibitor, was developed by fusing TβRII-SE, a soluble TGF-β type II receptor (TβRII) peptide encoded by a novel splice variant, to the Fc portion of human IgG (TβRII-SE/Fc). Previous results evidence the potential effect of Br against metabolic syndrome. Thus, we aimed to study the effect of lentiviral-mediated liver overexpression of Br (Lv-Br) on lipid metabolism in a rat model of MAFLD induced by Western Diet (WD). We compared three groups: control, WD, and WD that received an intrahepatic injection of the lentiviral vector encoding Br (WD+Lv-Br) at week 10. In week 20, WD+Lv-Br group had a lower abdominal circumference than WD group(p