Pathogenesis roles of
phospholipids (PLs) in
nonalcoholic fatty liver disease (
NAFLD) remain incompletely understood. This study investigated the role of PLs in the progression of
NAFLD among obese individuals via studying the alterations in serum PL composition throughout the spectrum of
disease progression and evaluating the effects of specific
phosphatidylethanolamines (PEs) on FLD development in vitro. A total of 203 obese subjects, who were undergoing
bariatric surgery, were included in this study. They were histologically classified into 80 controls (C) with normal liver histology, 93 patients with simple hepatic steatosis (SS), 16 with borderline
nonalcoholic steatohepatitis (B-NASH) and 14 with progressive NASH (NASH). Serum PLs were profiled by automated electrospray ionization tandem mass spectrometry (ESI-MS/MS). HepG2 (
hepatoma cells) and LX2 (immortalized hepatic stellate cells or HSCs) were used to explore the roles of PL in
NAFLD/NASH development. Several PLs and their relative ratios were significantly associated with
NAFLD progression, especially those involving PE. Incubation of HepG2 cells with two
phosphatidylethanolamines (PEs), PE (34:1) and PE (36:2), resulted in significant inhibition of cell proliferation, reduction of mitochondrial mass and membrane potential, induction of
lipid accumulation and mitochondrial ROS production. Meanwhile, treatment of LX2 cells with both PEs markedly increased cell activation and migration. These effects were associated with a significant change in the expression levels of genes involved in lipogenesis,
lipid oxidation, autophagy, apoptosis,
inflammation, and
fibrosis. Thus, our study demonstrated that elevated level of PEs increases susceptibility to the
disease progression of
obesity associated
NAFLD, likely through a causal cascade of impacts on the function of different liver cells.