title: The Association of Human Apolipoprotein C-III Sialylation Proteoforms with Plasma Triglycerides.
abstract: BACKGROUND
  Apolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III0a without glycosylation and apoC-III0b with glycosylation), monosialylated (apoC-III1) or disialylated (apoC-III2) proteoforms. Our aim was to clarify the relationship between apoC-III sialylation proteoforms with fasting plasma TG concentrations.
  
  
  METHODS
  In 204 non-diabetic adolescent participants, the relative abundance of apoC-III plasma proteoforms was measured using mass spectrometric immunoassay.
  
  
  RESULTS
  Compared with the healthy weight subgroup (n = 16), the ratios of apoC-III0a, apoC-III0b, and apoC-III1 to apoC-III2 were significantly greater in overweight (n = 33) and obese participants (n = 155). These ratios were positively correlated with BMI z-scores and negatively correlated with measures of insulin sensitivity (Si). The relationship of apoC-III1 / apoC-III2 with Si persisted after adjusting for BMI (p = 0.02). Fasting TG was correlated with the ratio of apoC-III0a / apoC-III2 (r = 0.47, p<0.001), apoC-III0b / apoC-III2 (r = 0.41, p<0.001), apoC-III1 / apoC-III2 (r = 0.43, p<0.001). By examining apoC-III concentrations, the association of apoC-III proteoforms with TG was driven by apoC-III0a (r = 0.57, p<0.001), apoC-III0b (r = 0.56. p<0.001) and apoC-III1 (r = 0.67, p<0.001), but not apoC-III2 (r = 0.006, p = 0.9) concentrations, indicating that apoC-III relationship with plasma TG differed in apoC-III2 compared with the other proteoforms.
  
  
  CONCLUSIONS
  We conclude that apoC-III0a, apoC-III0b, and apoC-III1, but not apoC- III2 appear to be under metabolic control and associate with fasting plasma TG. Measurement of apoC-III proteoforms can offer insights into the biology of TG metabolism in obesity.
authors.affiliation: Department of Medicine, University of Southern California, Los Angeles, United States of America.
authors.forename: Hussein N
authors.initials: HN
authors.lastname: Yassine
authors.affiliation: The Biodesign Institute, Arizona State University, Tempe, AZ, United States of America.
authors.forename: Olgica
authors.initials: O
authors.lastname: Trenchevska
authors.affiliation: Department of Medicine, University of Southern California, Los Angeles, United States of America.
authors.forename: Ambika
authors.initials: A
authors.lastname: Ramrakhiani
authors.affiliation: Department of Medicine, University of Southern California, Los Angeles, United States of America.
authors.forename: Aarushi
authors.initials: A
authors.lastname: Parekh
authors.affiliation: Department of Medicine, Phoenix Veteran Affairs Medical Center, Phoenix, AZ, United States of America.
authors.forename: Juraj
authors.initials: J
authors.lastname: Koska
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, United States of America.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Walker
authors.affiliation: Biostatics Consulting Lab, University of Arizona, Tucson, AZ, United States of America.
authors.forename: Dean
authors.initials: D
authors.lastname: Billheimer
authors.affiliation: Department of Medicine, Phoenix Veteran Affairs Medical Center, Phoenix, AZ, United States of America.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Reaven
authors.affiliation: Université de Lorraine, URAFPA, INSERM, Vandoeuvre-lès-Nancy, France.
authors.forename: Frances T
authors.initials: FT
authors.lastname: Yen
authors.affiliation: The Biodesign Institute, Arizona State University, Tempe, AZ, United States of America.
authors.forename: Randall W
authors.initials: RW
authors.lastname: Nelson
authors.affiliation: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Goran
authors.affiliation: The Biodesign Institute, Arizona State University, Tempe, AZ, United States of America.
authors.forename: Dobrin
authors.initials: D
authors.lastname: Nedelkov
mesh_terms: D000293:Adolescent; D053305:Apolipoprotein C-III / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology*; D002648:Child; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D050177:Overweight / Q000097:blood / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood*
chemical_list: D053305:Apolipoprotein C-III; D014280:Triglycerides