title: Platelet functional and transcriptional changes induced by intralipid infusion.
abstract: Multiple studies have shown the effects of long-term exposure to high-fat or western diets on the vascular system. There is limited knowledge on the acute effects of high circulating fat levels, specifically on platelets, which have a role in many processes, including thrombosis and inflammation. This study investigated the effects of acute, high-fat exposure on platelet function and transcript profile. Twenty healthy participants were given an intravenous infusion of 20% Intralipid emulsion and heparin over 6 hours. Blood samples were taken prior to and the day after infusion to measure platelet function and transcript expression levels. Platelet aggregation was not significantly affected by Intralipid infusion, but, when mitochondria function was inhibited by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) or oligomycin, platelet aggregation was higher in the post-infusion state compared to baseline. Through RNA sequencing, and verified by RT-qPCR, 902 miRNAs and 617 mRNAs were affected by Intralipid infusion. MicroRNAs increased include miR-4259 and miR-346, while miR-517b and miR-517c are both decreased. Pathway analysis identified two clusters significantly enriched, including cell motility. In conclusion, acute exposure to high fat affects mitochondrial-dependent platelet function, as well as the transcript profile.
authors.forename: Lea M
authors.initials: LM
authors.lastname: Beaulieu
authors.forename: Olga
authors.initials: O
authors.lastname: Vitseva
authors.forename: Kahraman
authors.initials: K
authors.lastname: Tanriverdi
authors.forename: Alper
authors.initials: A
authors.lastname: Kucukural
authors.forename: Eric
authors.initials: E
authors.lastname: Mick
authors.forename: Naomi
authors.initials: N
authors.lastname: Hamburg
authors.forename: Joseph
authors.initials: J
authors.lastname: Vita
authors.affiliation: Jane E. Freedman, University of Massachusetts Medical School, 368 Plantation St. ASC7-1051, Worcester, MA 01605, USA, Tel.: +1 508 856 6961, E-mail: jane.freedman@umassmed.edu.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Freedman
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D004655:Emulsions / Q000008:administration & dosage; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D010743:Phospholipids / Q000008:administration & dosage*; D010974:Platelet Aggregation; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D020537:RNA, Small Nucleolar / Q000097:blood / Q000235:genetics; D013024:Soybean Oil / Q000008:administration & dosage*; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D004655:Emulsions; D035683:MicroRNAs; D010743:Phospholipids; D012333:RNA, Messenger; D020537:RNA, Small Nucleolar; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil
keywords: Clinical studies; gene expression; obesity; platelet physiology