Plasma proteomic profile of abdominal obesity in older adults

Abstract

Objective: This study examines the plasma proteomic profile of abdominal obesity in older adults.

Methods: The association of abdominal obesity (waist circumference [WC]) with 4265 plasma proteins identified using the SomaScan Assay was examined in 969 Ashkenazi Jewish participants (LonGenity cohort), aged 65 years and older (mean [SD] age 75.7 [6.7] years, 55.4% women), using regression models. Pathway analysis, as well as weighted correlation network analysis, was performed. WC was determined from the proteome using elastic net regression.

Results: A total of 480 out of 4265 proteins were associated with WC in the linear regression model. Leptin (β [SE] = 12.363 [0.490]), inhibin β C chain (INHBC; β [SE] = 24.324 [1.448]), insulin-like growth factor-binding protein 2 (IGFBP-2; β [SE] = -12.782 [0.841]), heparan-sulfate 6-O-sulfotransferase 3 (H6ST3; β [SE] = -39.995 [2.729]), and matrix-remodeling-associated protein 8 (MXRA8; β [SE] = -27.101 [1.850]) were the top proteins associated with WC. Cell adhesion, extracellular matrix remodeling, and IGF transport pathways were the top enriched pathways associated with WC. WC signature determined from plasma proteins was highly correlated with measured WC (r = 0.80) and was associated with various metabolic and physical traits.

Conclusions: The study unveiled a multifaceted plasma proteomic profile of abdominal obesity in older adults, offering insights into its wide-ranging impact on the proteome. It also elucidated novel proteins, clusters of correlated proteins, and pathways that are intricately associated with abdominal obesity.

Figure 1. Association of proteins with waist circumference

Volcano plot showing associated proteins as red dots (p-value<1.0×10⁻⁵) X-axis denotes the Beta estimates coefficient from linear model and Y-axis shows the significance level presented as –log₁₀ (p-value). Top proteins have been annotated. Models were adjusted for age, gender and cohort status

Figure 2.. Correlation of waist circumference (WC) and abundance of top proteins stratified by gender.

The x-axis denotes the WC (centimeters), and the y-axis shows the SOMAmer abundance expressed in log scale.

Figure 3.. Correlation of measured waist circumference and predicted waist circumference in (a) training and (b) validation set

Waist circumference prediction carried out using elastic net regression method in 569 participants in training set and 400 participants in the validation set. Correlation of predicted waist circumference in training set itself was 0.92 while in validation it was 0.82