Plasma Protein Profiling Reveals Protein Clusters Related to BMI and Insulin Levels in Middle-Aged Overweight Subjects

Abstract

BackgroundBiomarkers that allow detection of the onset of disease are of high interest since early detection would allow intervening with lifestyle and nutritional changes before the disease is manifested and pharmacological therapy is required. Our study aimed to improve the phenotypic characterization of overweight but apparently healthy subjects and to identify new candidate profiles for early biomarkers of obesity-related diseases such as cardiovascular disease and type 2 diabetes.Methodology/Principal FindingsIn a population of 56 healthy, middle-aged overweight subjects Body Mass Index (BMI), fasting concentration of 124 plasma proteins and insulin were determined. The plasma proteins are implicated in chronic diseases, inflammation, endothelial function and metabolic signaling. Random Forest was applied to select proteins associated with BMI and plasma insulin. Subsequently, the selected proteins were analyzed by clustering methods to identify protein clusters associated with BMI and plasma insulin. Similar analyses were performed for a second population of 20 healthy, overweight older subjects to verify associations found in population I. In both populations similar clusters of proteins associated with BMI or insulin were identified. Leptin and a number of pro-inflammatory proteins, previously identified as possible biomarkers for obesity-related disease, e.g. Complement 3, C Reactive Protein, Serum Amyloid P, Vascular Endothelial Growth Factor clustered together and were positively associated with BMI and insulin. IL-3 and IL-13 clustered together with Apolipoprotein A1 and were inversely associated with BMI and might be potential new biomarkers.Conclusion/ SignificanceWe identified clusters of plasma proteins associated with BMI and insulin in healthy populations. These clusters included previously reported biomarkers for obesity-related disease and potential new biomarkers such as IL-3 and IL-13. These plasma protein clusters could have potential applications for improved phenotypic characterization of volunteers in nutritional intervention studies or as biomarkers in the early detection of obesity-linked disease development and progression.

Responses to High-Fat Challenges Varying in Fat Type in Subjects with Different Metabolic Risk Phenotypes: A Randomized Trial

“…Whole genome transcriptome, proteome or metabolome profiling tools could be used for more extensive characterization of the challenge response. As shown in previous studies, extensive profiling could identify subtle changes of genes, proteins or metabolites in pathways and clusters [14], [36]. The combination of challenge tests and extensive profiling may reveal changes in health status at a very early stage [37].…”

Altered serum levels of interleukin-3 in first-episode drug-naive and chronic medicated schizophrenia

“…Seventh, we did not control for some confounders, especially BMI. A study found that IL-3 and IL-13 clustered together with apolipoprotein A1 and were inversely associated with BMI in healthy, middleaged overweight subjects (van Dijk et al, 2010). Hence, the altered IL-3 in patients may be related to differential body weight and metabolic syndrome that could be the result of prolonged antipsychotic medication in vulnerable patients.…”

A Consideration of Biomarkers to be Used for Evaluation of Inflammation in Human Nutritional Studies

“…In a more recent study, a large set of plasma proteins related to chronic diseases, inflammation, endothelial function and metabolic signalling was assessed in a population of relatively healthy, middle-aged, overweight subjects ( 291 , 292 ) . Clusters of proteins associated with BMI or insulin were identified.…”