PMID- 27833848 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 2211-5463 (Print) IS - 2211-5463 (Electronic) IS - 2211-5463 (Linking) VI - 6 IP - 11 DP - 2016 Nov TI - Neutral ceramidase-enriched exosomes prevent palmitic acid-induced insulin resistance in H4IIEC3 hepatocytes. PG - 1078-1084 AB - 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. FAU - Zhu, Qun AU - Zhu Q AD - 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. FAU - Zhu, Rongping AU - Zhu R AD - Laboratory of Hepatobiliary and Pancreatic Surgery Affiliated Hospital of Guilin Medical University Guangxi China. FAU - Jin, Junfei AU - Jin J AD - 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. LA - eng PT - Journal Article DEP - 20161020 PL - England TA - FEBS Open Bio JT - FEBS open bio JID - 101580716 PMC - PMC5095145 OTO - NOTNLM OT - ceramide OT - exosome OT - insulin resistance OT - neutral ceramidase OT - palmitic acid OT - reactive oxygen species EDAT- 2016/11/12 06:00 MHDA- 2016/11/12 06:01 PMCR- 2016/10/20 CRDT- 2016/11/12 06:00 PHST- 2016/06/20 00:00 [received] PHST- 2016/08/25 00:00 [revised] PHST- 2016/08/27 00:00 [accepted] PHST- 2016/11/12 06:00 [entrez] PHST- 2016/11/12 06:00 [pubmed] PHST- 2016/11/12 06:01 [medline] PHST- 2016/10/20 00:00 [pmc-release] AID - FEB412125 [pii] AID - 10.1002/2211-5463.12125 [doi] PST - epublish SO - FEBS Open Bio. 2016 Oct 20;6(11):1078-1084. doi: 10.1002/2211-5463.12125. eCollection 2016 Nov.