Gene expression profile of CD14+ blood monocytes following lifestyle-induced weight loss in individuals with metabolic syndrome

Ronald Biemann, Kirsten Roomp, Fozia Noor, Shruthi Krishnan, Zhen Li, Khurrum Shahzad, Katrin Borucki, Claus Luley, Jochen G Schneider, Berend Isermann, Ronald Biemann, Kirsten Roomp, Fozia Noor, Shruthi Krishnan, Zhen Li, Khurrum Shahzad, Katrin Borucki, Claus Luley, Jochen G Schneider, Berend Isermann

Abstract

Lifestyle-induced weight loss is regarded as an efficient therapy to reverse metabolic syndrome (MetS) and to prevent disease progression. The objective of this study was to investigate whether lifestyle-induced weight loss modulates gene expression in circulating monocytes. We analyzed and compared gene expression in monocytes (CD14+ cells) and subcutaneous adipose tissue biopsies by unbiased mRNA profiling. Samples were obtained before and after diet-induced weight loss in well-defined male individuals in a prospective controlled clinical trial (ICTRP Trial Number: U1111-1158-3672). The BMI declined significantly (- 12.6%) in the treatment arm (N = 39) during the 6-month weight loss intervention. This was associated with a significant reduction in hsCRP (- 45.84%) and circulating CD14+ cells (- 21.0%). Four genes were differentially expressed (DEG's) in CD14+ cells following weight loss (ZRANB1, RNF25, RB1CC1 and KMT2C). Comparative analyses of paired CD14+ monocytes and subcutaneous adipose tissue samples before and after weight loss did not identify common genes differentially regulated in both sample types. Lifestyle-induced weight loss is associated with specific changes in gene expression in circulating CD14+ monocytes, which may affect ubiquitination, histone methylation and autophagy.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Relationship between changes in CD14+ cell frequencies and clinical or laboratory parameters. Spearman correlation (2-tailed) was used to analyze the correlation between relative changes in CD14+ cell frequencies and BMI (a), leptin (b) or hsCRP (c) in participants of both arms. Data are shown as individual data points. The regression line is given as the mean ± 95% confidence interval.
Figure 2
Figure 2
Principal component analysis. The principal component analysis (PCA) plot was used to visualize the variance in gene expression data in participants of the treatment arm at baseline (red symbols) and after the 6-month intervention period (blue symbols). The first principal component (PC1) on the x-axis is the linear combination comprising the largest percentage of variation in the dataset. The second principal component (PC2), located on the y-axis, captures the second largest percentage of variance. PCA was generated using the affycoretools package in R (R Core Team, 2018, R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna. https://www.R-project.org).
Figure 3
Figure 3
Principal component analysis of CD14+ and subcutaneous adipose tissue samples before and after weight loss. The principal component analysis (PCA) plot was used to visualize the variance in gene expression between corresponding CD14+ and subcutaneous adipose tissue samples each before (red, blue) and after (green, purple) weight loss (N = 36). The first principal component (PC1) on the x-axis is the linear combination comprising the largest percentage of variation in the dataset. The second principal component (PC2), located on the y-axis, captures the second largest percentage of variance. PCA was generated using the affycoretools package in R (R Core Team, 2018, R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna. https://www.R-project.org).
Figure 4
Figure 4
Schematic study design. The study is embedded in a two-armed, controlled, monocentric, randomized, 6-month intervention trial. Paired blood samples were collected before and after the 6-months intervention period. Individuals of the control arm were invited during the follow-up period to participate subsequently in the treatment arm. Samples from participants of the control arm who lost more than 0.5 kg of weight during the study period and samples with low RNA quality were excluded from analysis. In total, 39 samples (treatment arm) and 12 samples (control arm) were used for unbiased gene expression profiling of purified CD14+ monocyte samples. Within the treatment arm, a subgroup characterized by an at least 50% reduction of elevated hsCRP following weight loss was analyzed (N = 16, hsCRP subgroup).

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