Fig 1: Liver-specific FGF21 knockout abrogated OVX-induced central obesity in mice. (A) Body weight profile of mice following OVX or the combination of OVX plus liver-specific FGF21 knockout. (B) The serum FGF21 concentrations in mice at decapitation. (C) Representative figures of mice indicating visceral adipose deposition at decapitation. (D) The average visceral fat weight of mice from each group. (E) Representative H&E staining of visceral adipose tissues of mice at decapitation. In figure A: * denotes p < 0.05 (OVX versus Sham/OVX+FGF21 LKO); in figure B and D: ** p < 0.01; *** p < 0.001, NS p > 0.05.
Fig 2: Liver-specific FGF21 knockout failed to rescue OVX-induced dyslipidemia and hepatic steatosis in mice. (A) Serum concentration of triglyceride (TG). (B) Serum concentration of free fat acid (FFA). (C) Liver weight. (D) Liver TG content. (E) The representative H&E staining of liver tissues from each group. Arrows indicate lipid droplets. * p < 0.05; ** p < 0.01; *** p < 0.001; NS p > 0.05.
Fig 3: Transcriptomic profiling revealing Hsd11b1 plays a central role in mediating FGF21 LKO on abrogating OVX-induced central obesity in mice. (A) Venn diagram of differentially expressed genes (DEGs) among groups. (B) The number of DEGs between pairwise groups. (C) The recovered DEGs (rDEGs) in OVX mice following FGF21 LKO. rDEGs are genes whose expression in OVX was significantly different from the sham controls but recovered back to the sham levels after FGF21 LKO. (D) The heat map of rDEGs involved in lipid metabolism process (GO:0006629). Red lines indicate DEGs between OVX+FGF21 LKO versus OVX. (E) Gene set enrichment analysis (GSEA) showed FGF21 LKO reduced adipogenesis in OVX mice, and leading-edge gene analysis highlighted that Hsd11b1 plays a major role in mediating FGF21 LKO on preventing adipogenesis in OVX mice.
Fig 4: FGF21 LKO reversed circulating high corticosterone but not high FSH in OVX mice. (A) Serum concentration of FSH. (B) Serum concentration of corticosterone. (C) Effects of transient recombinant FGF21 replacement on serum concentration of corticosterone in OVX+FGF21 LKO mice. (D) Effects of transient recombinant FGF21 replacement on visceral adipose Hsd11b1 expression in OVX+FGF21 LKO mice. * p < 0.05; ** p < 0.01; *** p < 0.001; NS p > 0.05.
Fig 5: FGF21 LKO reduced serum insulin levels in OVX mice. (A) Serum concentration of insulin; (B) Gene set enrichment analysis indicated FGF21 LKO reduced SREBF-mediated lipogenesis. (C) Gene set enrichment analysis indicated FGF21 LKO even reduced insulin signaling in OVX mice compared to the sham controls. *** p < 0.001.
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