Values are presented as means ± SEM and expressed relative to the respective control group. Group differences were assessed by Student’s t test, one-way analysis of variance (ANOVA), or two-way ANOVA where appropriate followed by Tukey’s post hoc test. Data were tested for normality before the use of a parametric test. Venn diagrams were created using the VennDiagram package (version 1.6.20) in R Studio. Gene overlaps presented in Fig. 1KESR1/Esr1 by gene correlations were calculated in adipose tissue from METSIM, MyoGlu, and HMDP studies using the midweight bicorrelation function in the weighted gene correlation network analysis package (version 1.67) in R Studio; significant correlations were set a priori as P < 0.001. Statistical significance of overlap for Venn diagrams was determined for each pairwise overlap using the hypergeometric probability formula. The represent ation factor (RF) indicates the fold change in observed versus expected overlap (R package version 1.24.0) (72 (link)). Statistical significance was established a priori at P < 0.05 for all other comparisons (GraphPad Prism 7.0).