Figure 6.

Adipose LCN2 downregulates expression of both LRP2 and ERα. Log₂ fold change expression values of A,Lcn2, Lrp2, and Esr1 between GFP and LCN2 overexpressing female adipose and B, their respective bicorrelations with adipose Lcn2 expression in female and male HMDP cohorts (n = 98 sex-matched strains). Relative normalized expression values of Lcn2, Lrp2, and Esr1 in C, female gonadal WAT D, male gonadal WAT E, female subcutaneous WAT and F, female BAT overexpressing GFP and LCN2, G – J,ex vivo pre- or differentiated primary inguinal or periovarian adipocytes isolated from female Lcn2-null or C57BL/6J wildtype mice treated with recombinant LCN2. Circos connectogram plot showing biweight midcorrelation between adipose K,Lrp2 or L,Esr1 expression and metabolic traits in female and male HMDP cohort (n = 102 female and 111 male strains). Each connecting line signify a significant (1% FDR cutoff) bicorrelation between Lrp2 or Esr1 expression and the respective trait. Blue line indicates negative correlation and the color intensity signify the magnitude of correlation. Data are presented as mean ± SEM (n = 4 mouse/group for global RNA sequencing; n = 4 mouse/group for qPCR; n = 6 female mouse/iWAT divided into two groups for ex vivo treatment). P values (and Q values for RNA sequencing data) were calculated by DESeq function of Bioconductor R-package for RNA sequencing; BicorAndPvalue function of the WGCNA R-package for HMDP transcript associations; Unpaired Student's t test for qPCR. *P or Q < 0.05; **P or Q < 0.01; ***P or Q < 0.001. See also Figures S1,S14–15 and Table S1.