Pulmonary Inflammation and Injury in a Mouse Model of Non-Alcoholic Steatohepatitis

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver condition that affects millions of individuals in the United States, of which approximately twenty percent of cases progress to non-alcoholic steatohepatitis (NASH). NASH is characterized by macrovascular steatosis and persistent inflammation in the liver, which can lead to fibrosis. Evidence suggests potential effects of NAFLD and NASH on the development of pulmonary pathologies, but the interaction between the liver and the lung is not well understood. In this study, we assessed the impact of NASH development on lung inflammation and fibrosis over time. Male C57BL/6J mice were fed control (10% kCal) or high-fat (HFD) (60% kCal) diets. Liver tissue, lung tissue, and bronchoalveolar lavage (BAL) fluid were collected after 1, 3, and 6 months of feeding. Histopathologic evaluation of livers from HFD-fed mice at 6 months confirmed the development of NASH. In the lung, we observed histopathologic alterations, including inflammatory cell infiltration, lipid-laden macrophages, septal damage, and epithelial thickening at 6 months. Gene expression analysis of whole lung tissue revealed changes in genes related to inflammation (IL-1B), fibrosis (CTGF), and lipid metabolism (ApoA1). These results characterize an association of pulmonary complications during simple steatosis to NASH transition, suggesting lung-liver crosstalk.