Mol Metab 2022 Aug 5:101566. Epub 2022 Aug 5.
Department of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA. 650 Charles E. Young Dr., Los Angeles, CA 90095 USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA. 650 Charles E. Young Dr., Los Angeles, CA 90095 USA; Molecular Biology Institute, University of California, Los Angeles, CA, USA at UCLA; Institut de Biologia Molecular de Barcelona, IBMB, CSIC, Baldiri Reixac 4-8, Barcelona, Catalonia, 08028, Spain. Electronic address:
Objective: The mitochondrial fission protein Drp1 was proposed to promote NAFLD, as inhibition of hepatocyte Drp1 early in life prevents liver steatosis induced by high-fat diet in mice. However, whether Drp1-knockdown in older mice can reverse established NASH is unknown.
Methods: N-acetylgalactosamine-siRNA conjugates, an FDA approved method to deliver siRNA selectively to hepatocytes, were used to knockdown hepatocyte-Drp1 in mice (NAG-Drp1si). Read More