Neutral ceramidase-enriched exosomes prevent palmitic acid-induced insulin resistance in H4IIEC3 hepatocytes.
Oversupply of free fatty acids such as palmitic acid (PA) from the portal vein may cause liver insulin resistance. Production of reactive oxygen species plays a pivotal role in PA-induced insulin resistance in H4IIEC3 hepatocytes. Recently, we found that exosomes secreted from INS-1 cells that were transfected with neutral ceramidase (NCDase) plasmids had raised NCDase activity; these NCDase-enriched exosomes could inhibit PA-induced INS-1 cell apoptosis. Here, we showed that PA reduced insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 2 and decreased insulin-stimulated uptake of the fluorescent glucose analog 2-NBDG, confirming that insulin resistance occurred in PA-treated H4IIEC3 cells. Moreover, NCDase-enriched exosomes from INS-1 cells rescued PA-induced H4IIEC3 insulin resistance and blocked PA-induced reactive oxygen species production in which ceramide was involved.
Department of Endocrinology the Second Affiliated Hospital of Nanjing Medical University Jiangsu China; China-USA Lipids in Health and Disease Research Center Guilin Medical University Guangxi China.
Qun
Q
Zhu
Laboratory of Hepatobiliary and Pancreatic Surgery Affiliated Hospital of Guilin Medical University Guangxi China.
Rongping
R
Zhu
China-USA Lipids in Health and Disease Research Center Guilin Medical University Guangxi China; Laboratory of Hepatobiliary and Pancreatic Surgery Affiliated Hospital of Guilin Medical University Guangxi China; Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair Guilin Medical University Guangxi China.
Junfei
J
Jin
ceramide; exosome; insulin resistance; neutral ceramidase; palmitic acid; reactive oxygen species