Proteomic profiles before and during weight loss: Results from randomized trial of dietary intervention

Abstract

Inflammatory and cardiovascular biomarkers have been associated with obesity, but little is known about how they change upon dietary intervention and concomitant weight loss. Further, protein biomarkers might be useful for predicting weight loss in overweight and obese individuals. We performed secondary analyses in the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized intervention trial that included healthy 609 adults (18-50 years old) with BMI 28-40 kg/m 2 , to evaluate associations between circulating protein biomarkers and BMI at baseline, during a weight loss diet intervention, and to assess predictive potential of baseline blood proteins on weight loss. We analyzed 263 plasma proteins at baseline and 6 months into the intervention using the Olink Proteomics CVD II, CVD III and Inflammation arrays. BMI was assessed at baseline, after 3 and 6 months of dietary intervention. At baseline, 102 of the examined inflammatory and cardiovascular biomarkers were associated with BMI (>90% with successful replication in 1,584 overweight/obese individuals from a community-based cohort study) and 130 tracked with weight loss shedding light into the pathophysiology of obesity. However, out of 263 proteins analyzed at baseline, only fibroblast growth factor 21 (FGF-21) predicted weight loss, and none helped individualize dietary assignment.

Inflammation-related plasma protein levels and association with adiposity measurements in young adults

“…The same study also demonstrated effect modification by sex in some of the associations. Longitudinal, large scale analysis of plasma proteins, that have been performed in predominantly select groups of patients, have shown that inflammatory patterns are influenced by weight loss and weight maintenance 15 – 17 , indicating potential benefit of a weight loss intervention. Similar patterns related to body fat and distribution have also been demonstrated in a population based study of elderly 26 .…”

“…Associations between adipose tissue and selected pro-inflammatory factors have been demonstrated in children, adolescents and adults 12 – 14 . Weight change and body mass index (BMI) have also been associated with several inflammation-related proteins in studies utilizing proteomic methods in cohorts of overweight and obese participants 15 – 17 .…”

Identification of Endothelial Proteins in Plasma Associated With Cardiovascular Risk Factors

“…Other screening technologies for CVD-relevant plasma proteins are available, such as commercial aptamer-based technology ( www.somalogic.com ) and proximity extension assays. 70 Such assays have been used to identify biomarkers associated with CVD risk factor exposure, such as blood lipids and BMI, 71 , 72 but these CVD screening panels are still primarily configured to detect proteins with known functions in pathophysiological processes and pathways involved in CVD (eg, inflammation, coagulation, lipid metabolism), and thus have limited overlap with our screening panel, which has a greater focus on biomarker source, rather than previous links to CVD. Furthermore, a significant number of candidates in such predeveloped screening panels have wide tissue or cell type expression, which can complicate interpretation of pathophysiological relevance of identified markers.…”

Identification of endothelial-derived proteins in plasma associated with cardiovascular risk factors

“…Other screening technologies for CVD relevant plasma proteins are available, such as commercial aptamer-based technology (www.somalogic.com) and proximity extension assays (PEA)(53). Such assays have been used to identify biomarkers associated with CVD risk factor exposure, such as blood lipids and BMI (54, 55), but these CVD screening panels are still primarily configured to detect proteins with known functions in pathophysiological processes and pathways involved in CVD (e.g. inflammation, coagulation, lipid metabolism), and thus have limited overlap with our screening panel, which has a greater focus on biomarker source, rather than previous links to CVD.…”

“…Conversely, proteins negatively associated with multiple CVD risk factors, HEG1, ADAMTSL4, FBLN2 and ANGPT2 are all normally secreted (69-72). Other studies have examined plasma protein association with CVD risk factor exposure and prediction using pre-designed PEA CVD panels; 102 proteins were identified as associated with baseline BMI in a study of weight loss over time, of which 88 were positively associated and 14 negatively associated (54) and 42 candidates were associated with at least one lipid fraction (triglycerides and total, LDL or HDL cholesterol) with multiple proteins overlapping groups (55). In a study of 899 participants without overt CVD in the Framingham Heart study Offspring cohort, 1129 proteins were measured, of which 156 were (positively or negatively) associated with Framingham risk score (73).…”