StarD7 modulates lipid metabolism in hepatic cells

FLORES MARTIN, JESICA B.; ROJAS, MARÍA L.; CERMINATO, PILAR; VEGA RODRIGUEZ, CANDELA; RACCA, ANA C.; PANZETTA-DUTARI, GRACIELA M.; GENTI-RAIMONDI, SUSANA

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias 2023, en la que participan la Sociedad Argentina de Investigación Clínica (SAIC); 2023

SAIC

StarD7 is a ubiquitous phosphatidylcholine transfer protein that belongs to the START superfamily, which are involved in metabolism, transport and intracellular signaling of lipids. Previous laboratoryreports indicate that cellular StarD7 deficiency alters mitochondrial morphology, functionality, and dynamics. Numerous evidences demonstrate that liver mitochondria play a critical role in the development of the pathogenesis of non-alcoholic fatty liver disease (NAFLD). NAFLD affects one quarter of the world’s population and may progress to non-alcoholic steatohepatitis (NASH), with risk of developing liver fibrosis and cancer. Here we evaluated the role of StarD7 in lipid metabolism in hepatic cell line HepG2. Stable HepG2 silenced of StarD7 (shD7), and its control (shC) were generated. A significant accumulation of lipid droplets (LDs) was observed in shD7 cells respect to shC, analyzed by fluorescence microscopy and flow cytometry. qRT-PCR and Western blot experiments demonstrated increased levels of transcripts and proteins of enzymes involved in de novo lipogenesis (FASN, ACLY, ACC, SCD and DGAT1) and increased CPT-1 protein involved in fatty acid transport across the mitochondrial inner membrane, in shD7 vs. shC. In addition, increased endoplasmic reticulum stress markers Ire1 and BIP/GRP78 were observed, while the antioxidant enzymes catalase and hemoxygenase 1 (HMOX1) were significantly decreased. Also, the levelsof reactive oxygen species (ROS) were raised in shD7 vs. shC cells, measured by flow cytometry. To determine the mechanism by which StarD7 modifies the regulation of de novo lipogenesis, thetranscription factor Srebp1 were measured. Increased expression of Srebp1 transcript and protein was demonstrated in shD7 relative to shC. Collectively, these results indicates that StarD7 depletion in HepG2 cells generates a model of metabolic syndrome similar to that described in NAFLD, contributing to the regulation of hepatic lipogenesis.