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
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.
"To date, any potential genetic markers or biomarkers of weight loss following bariatric surgery have been limited by clinical utility, and sensitivity and specificity [38,39]. Some data identifying potential markers of weight loss are inadequately controlled and unmatched . "
[Show abstract][Hide abstract] ABSTRACT: Obesity is recognized as a global health crisis. Bariatric surgery offers a treatment that can reduce weight, induce remission of obesity-related diseases, and improve the quality of life. In this article, we outline the different options in bariatric surgery and summarize the recommendations for selecting and assessing potential candidates before proceeding to surgery. We present current data on post-surgical outcomes and evaluate the psychosocial and economic effects of bariatric surgery. Finally, we evaluate the complication rates and present recommendations for post-operative care.
BMC Medicine 01/2013; 11(1):8. DOI:10.1186/1741-7015-11-8 · 7.25 Impact Factor
"The role of APOC3 is to inhibit lipoprotein lipase and hepatic lipase in order to decrease the general uptake by the hepatic cells. Studies have shown that HIV-1 patients possess increased levels of APOC3 (Bard et al., 2006), whereas other reports have found that APOC3 responds to stimuli in obese patients who have been affected by diseases such as hepatitis C (Harvey et al., 2009). APOB is another protein related to HCV progression. "
[Show abstract][Hide abstract] ABSTRACT: The analysis of plasma samples from HIV-1/HCV mono- and coinfected individuals by quantitative proteomics is an efficient strategy to investigate changes in protein abundances and to characterize the proteins that are the effectors of cellular functions involved in viral pathogenesis. In this study, the infected and healthy plasma samples (in triplicate) were treated with ProteoMiner beads to equalize protein concentrations and subjected to 4-plex iTRAQ labeling and liquid chromatography/mass spectrometry (LC-MS/MS) analysis. A total of 70 proteins were identified with high confidence in the triplicate analysis of plasma proteins and 65% of the proteins were found to be common among the three replicates. Apolipoproteins and complement proteins are the two major classes of proteins that exhibited differential regulation. The results of quantitative analysis revealed that APOA2, APOC2, APOE, C3, HRG proteins were upregulated in the plasma of all the three HIV-1 mono-, HCV mono-, and coinfected patient samples compared to healthy control samples. Ingenuity pathway analysis (IPA) of the upregulated proteins revealed that they are implicated in the hepatic lipid metabolism, inflammation, and acute-phase response signaling pathways. Thus, we identified several differentially regulated proteins in HIV-1/HCV mono and coinfected plasma samples that may be potential biomarkers for liver disease.
Omics: a journal of integrative biology 10/2011; 15(10):705-17. DOI:10.1089/omi.2011.0004 · 2.36 Impact Factor
"The quantitative changes of serum Hp, as well as the well known acute-phase reactants found in this study, such as apolipoproteins A-IV, complement C4 and serum amyloid A thus might reflect changes in these proteins as manifestation of their roles in the pathophysiologic development and propagation of cGVHD or, alternatively, simply a nonspecific manifestation of an inflammatory state. Other investigators have described results that differ from the data reported here in terms of some acute phase reactants such as apolipoproteins in the setting of GVHD . However, these data were derived from patients undergoing cord blood transplantation in contrast to our data set which is derived from patients receiving only adult derived hematopoietic stem cell transplantation. "
[Show abstract][Hide abstract] ABSTRACT: We studied serum proteomic profiling in patients with graft versus host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) by two-dimensional gel electrophoresis (2-DE) and mass spectrometry analysis. The expression of a group of proteins, haptoglobin (Hp), alpha-1-antitrypsin, apolipoprotein A-IV, serum paraoxonase and Zn-alpha-glycoprotein were increased and the proteins, clusterin precursor, alpha-2-macroglobulin, serum amyloid protein precursor, sex hormone-binding globulin, serotransferrin and complement C4 were decreased in patients with extensive chronic GVHD (cGVHD). Serum haptoglobin (Hp) levels in patients with cGVHD were demonstrated to be statistically higher than in patients without cGVHD and normal controls (p < 0.01). We used immunoblotting and PCR in combination with 2-DE gel image analysis to determine Hp polymorphisms in 25 allo-HCT patients and 16 normal donors. The results demonstrate that patients with cGVHD had a higher incidence of HP 2-2 phenotype (43.8%), in comparison to the patients without cGVHD (0%) and normal donors (18.7%), suggesting the possibility that specific Hp polymorphism may play a role in the development of cGVHD after allo-HCT. In this study, quantitative serum Hp levels were shown to be related to cGVHD development. Further, the data suggest the possibility that specific Hp polymorphisms may be associated with cGVHD development and warrant further investigation.
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