title: O-glycoside biomarker of apolipoprotein C3: responsiveness to obesity, bariatric surgery, and therapy with metformin, to chronic or severe liver disease and to mortality in severe sepsis and graft vs host disease.
abstract: The glyco-isoforms of intact apolipoprotein C3 (ApoC3) were used to probe glycomic changes associated with obesity and recovery following bariatric surgery, liver diseases such as chronic hepatitis C (CHC) and alcoholic liver cirrhosis, as well as severe, multiorgan diseases such as sepsis and graft vs host disease (GVHD). ApoC3 glyco-isoform ratios responded to unique stimuli that did not correlate with serum lipids or with other blood components measured in either a control population or a group of extremely obese individuals. However, glyco-isoform ratios correlated with obesity with a 1.8-fold change among subjects eligible for bariatric surgery relative to a nonobese control population. Bariatric surgery resulted in rapid change of isoform distribution to that of nonobese individuals, after which the distribution was stable in each individual. Although multiple simultaneous factors complicated effector attribution, the isoform ratios of very obese individuals were nearly normal for diabetic individuals on metformin therapy. Glyco-isoform ratios were sensitive to liver diseases such as chronic hepatitis C and alcoholic liver cirrhosis. The correlation coefficient with fibrosis was superior to that of current assays of serum enzyme levels. Diseases of pregnancy that can result in liver damage, HELLP syndrome and pre-eclampsia, did not alter ApoC3 glyco-isoform ratios. Early after umbilical cord blood transplantation the isoform ratios changed and returned to normal in long-term survivors. Larger changes were observed in persons who died. GVHD had little effect. Persons with severe sepsis showed altered ratios. Similar cut-points for mortality (3.5-fold difference from controls) were found for UCBT and sepsis. Similar values characterized liver cirrhosis. Overall, while changes of glyco-isoform ratios occurred in many situations, individual stability of isoform distribution was evident and large changes were limited to high-level disease. If ratio changes associated with obesity are found to document a risk factor for long-term outcomes, the information provided by glyco-isoform ratio changes may provide important, novel information for diagnostic, prognostic and therapy response to metabolic conditions.
authors.affiliation: Department of Biochemistry, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Harvey
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Joshua
authors.initials: J
authors.lastname: Wilson-Grady
authors.forename: Teresa
authors.initials: T
authors.lastname: Monkkonen
authors.forename: Gary L
authors.initials: GL
authors.lastname: Nelsestuen
authors.forename: Raj S
authors.initials: RS
authors.lastname: Kasthuri
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
authors.forename: Troy C
authors.initials: TC
authors.lastname: Lund
authors.forename: E Wesley
authors.initials: EW
authors.lastname: Ely
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Bernard
authors.forename: Harald
authors.initials: H
authors.lastname: Zeisler
authors.forename: Monika
authors.initials: M
authors.lastname: Homoncik
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
authors.forename: Therese
authors.initials: T
authors.lastname: Swan
authors.forename: Todd A
authors.initials: TA
authors.lastname: Kellogg
mesh_terms: D000328:Adult; D000368:Aged; D053305:Apolipoprotein C-III / Q000097:blood / Q000737:chemistry; D050110:Bariatric Surgery; D015415:Biomarkers / Q000097:blood / Q000737:chemistry; D003920:Diabetes Mellitus / Q000188:drug therapy; D005260:Female; D006027:Glycosides / Q000737:chemistry*; D006086:Graft vs Host Disease / Q000097:blood / Q000401:mortality; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008107:Liver Diseases / Q000097:blood*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000601:surgery; D011247:Pregnancy; D020033:Protein Isoforms / Q000097:blood / Q000737:chemistry; D018805:Sepsis / Q000097:blood / Q000401:mortality
chemical_list: D053305:Apolipoprotein C-III; D015415:Biomarkers; D006027:Glycosides; D007004:Hypoglycemic Agents; D020033:Protein Isoforms; D008687:Metformin