Weight Changes Are Linked to Adipose Tissue Genes in Overweight Women with Polycystic Ovary Syndrome

Abstract

Women with polycystic ovary syndrome (PCOS) have varying difficulties in achieving weight loss by lifestyle intervention, which may depend on adipose tissue metabolism. The objective was to study baseline subcutaneous adipose tissue gene expression as a prediction of weight loss by lifestyle intervention in obese/overweight women with PCOS. This is a secondary analysis of a randomized controlled trial where women with PCOS, aged 18-40 and body mass index (BMI) ≥ 27 were initially randomized to either a 4-month behavioral modification program or minimal intervention according to standard care. Baseline subcutaneous adipose tissue gene expression was related to weight change after the lifestyle intervention. A total of 55 obese/overweight women provided subcutaneous adipose samples at study entry. Weight loss was significant after behavioral modification (-2.2%, p = 0.0014), while there was no significant weight loss in the control group (-1.1%, p = 0.12). In microarray analysis of adipose samples, expression of 40 genes differed significantly between subgroups of those with the greatest weight loss or weight gain. 10 genes were involved in metabolic pathways including glutathione metabolism, gluconeogenesis, and pyruvate metabolism. Results were confirmed by real-time polymerase chain reaction (RT-PCR) in all 55 subjects. Expressions of GSTM5, ANLN, and H3C2 correlated with weight change (R = -0.41, p = 0.002; R = -0.31, p = 0.023 and R = -0.32, p = 0.016, respectively). GSTM5, involved in glutathione metabolism, was the strongest predictor of weight loss, and together with baseline waist-hip ratio (WHR) explained 31% of the variation in body weight change. This study shows that baseline subcutaneous adipose tissue genes play a role for body weight outcome in response to lifestyle intervention in overweight/obese women with PCOS.

Keywords: PCOS; adipose tissue; gene expression; lifestyle; obesity; weight loss.

Figure 1

Weight change (%) after 4 months of intervention in the behavioral modification group and the minimal intervention group (control treatment). Results presented as mean change from baseline and confidence interval. Body weight decreased significantly (p = 0.0014, represented by **) in the behavioral modification group but not in the control treatment group. There was no significant difference between the two treatment groups (p = 0.24).

Figure 2

(a–j). Relative expression of (a) GSTM5, (b) RRM2, (c) ANLN, (d) ANPEP, (e) TOP2A, (f) STMN1;MIR3917, (g) H3C2, (h) PFKB1, (i) ACLY, and (j) PC of the whole sample (n = 55) divided into the 50th centile of weight change from baseline into a Weight loss group and a Weight gain group. (a) GSTM5 and (g) H3C2 differed significantly in relative expression between the groups, p = 0.01 and p = 0.045, respectively. Black dots represent extreme values. ns = Not significant.

Figure 3

(a–d). Correlation between individual relative expression values of (a) GSTM5, (b) RRM2, (c) ANLN and (d) H3C2 (n = 55) and change in weight (Weight Change) for the whole sample (n = 55). Pearson correlation with regression line and confidence intervals were used for statistical analysis of (a) GSTM5 and (b) RRM2. Spearman correlations were used for statistical analysis of (c) ANLN, and (d) H3C2.

Figure 4

Receiver operating characteristic (ROC) curve of GSTM5 and WHR for prediction of weight loss (%) in the whole sample (n = 55). Dashed line represents random line. Blue solid line represents fitted curve.

Figure 5

Diagram of the study design.