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a–c, Total ( a ), essential ( b ), and branched-chain ( c ) amino acid concentrations in portal and cava veins at P56, in postprandial state. d, Heatmap of postabsorptive hepatic amino acid concentrations at P56, stratified by sex and diet. e, Enriched KEGG pathways from gene set enrichment analysis (GSEA; adjusted P < 0.05), in males (top) and females (bottom), curated using amino acid metabolism–related gene sets from Green et al. (2022). Pathways related to amino acid metabolism and nutrient stress are highlighted in red. f, Volcano plots of liver transcriptomes in males (top) and females (bottom), showing differentially expressed genes (DEGs; FDR□<□0.05, |log 2 FC|□>□1). Selected nutrient stress–responsive genes are highlighted in red. g , Heatmap of relative expression of BCAA-related catabolic genes, transporters (black box) and downstream targets. h–i, Heatmap of relative expression of canonical ATF4 ( h ) and PPARα ( i ) target genes in the liver. j , Hepatic <t>Fgf21</t> expression (log 2 relative to reference genes) in males and females, at P28, P42 and P70. k , Circulating FGF21 concentrations (serum) in males and females, from P28 to P70. Unless otherwise stated, data are mean ± sd; symbols indicate post hoc significance of diet effect (* P □<□0.05, ** P □<□0.01, *** P □<□0.001), ns , not significant. The number of mice used in each panel is provided in Extended Data Table 2 .
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a–c, Total ( a ), essential ( b ), and branched-chain ( c ) amino acid concentrations in portal and cava veins at P56, in postprandial state. d, Heatmap of postabsorptive hepatic amino acid concentrations at P56, stratified by sex and diet. e, Enriched KEGG pathways from gene set enrichment analysis (GSEA; adjusted P < 0.05), in males (top) and females (bottom), curated using amino acid metabolism–related gene sets from Green et al. (2022). Pathways related to amino acid metabolism and nutrient stress are highlighted in red. f, Volcano plots of liver transcriptomes in males (top) and females (bottom), showing differentially expressed genes (DEGs; FDR□<□0.05, |log 2 FC|□>□1). Selected nutrient stress–responsive genes are highlighted in red. g , Heatmap of relative expression of BCAA-related catabolic genes, transporters (black box) and downstream targets. h–i, Heatmap of relative expression of canonical ATF4 ( h ) and PPARα ( i ) target genes in the liver. j , Hepatic <t>Fgf21</t> expression (log 2 relative to reference genes) in males and females, at P28, P42 and P70. k , Circulating FGF21 concentrations (serum) in males and females, from P28 to P70. Unless otherwise stated, data are mean ± sd; symbols indicate post hoc significance of diet effect (* P □<□0.05, ** P □<□0.01, *** P □<□0.001), ns , not significant. The number of mice used in each panel is provided in Extended Data Table 2 .
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a–c, Total ( a ), essential ( b ), and branched-chain ( c ) amino acid concentrations in portal and cava veins at P56, in postprandial state. d, Heatmap of postabsorptive hepatic amino acid concentrations at P56, stratified by sex and diet. e, Enriched KEGG pathways from gene set enrichment analysis (GSEA; adjusted P < 0.05), in males (top) and females (bottom), curated using amino acid metabolism–related gene sets from Green et al. (2022). Pathways related to amino acid metabolism and nutrient stress are highlighted in red. f, Volcano plots of liver transcriptomes in males (top) and females (bottom), showing differentially expressed genes (DEGs; FDR□<□0.05, |log 2 FC|□>□1). Selected nutrient stress–responsive genes are highlighted in red. g , Heatmap of relative expression of BCAA-related catabolic genes, transporters (black box) and downstream targets. h–i, Heatmap of relative expression of canonical ATF4 ( h ) and PPARα ( i ) target genes in the liver. j , Hepatic Fgf21 expression (log 2 relative to reference genes) in males and females, at P28, P42 and P70. k , Circulating FGF21 concentrations (serum) in males and females, from P28 to P70. Unless otherwise stated, data are mean ± sd; symbols indicate post hoc significance of diet effect (* P □<□0.05, ** P □<□0.01, *** P □<□0.001), ns , not significant. The number of mice used in each panel is provided in Extended Data Table 2 .

Journal: bioRxiv

Article Title: Liver FGF21 mediates sex-specific adaptation to juvenile protein malnutrition

doi: 10.1101/2025.07.09.663702

Figure Lengend Snippet: a–c, Total ( a ), essential ( b ), and branched-chain ( c ) amino acid concentrations in portal and cava veins at P56, in postprandial state. d, Heatmap of postabsorptive hepatic amino acid concentrations at P56, stratified by sex and diet. e, Enriched KEGG pathways from gene set enrichment analysis (GSEA; adjusted P < 0.05), in males (top) and females (bottom), curated using amino acid metabolism–related gene sets from Green et al. (2022). Pathways related to amino acid metabolism and nutrient stress are highlighted in red. f, Volcano plots of liver transcriptomes in males (top) and females (bottom), showing differentially expressed genes (DEGs; FDR□<□0.05, |log 2 FC|□>□1). Selected nutrient stress–responsive genes are highlighted in red. g , Heatmap of relative expression of BCAA-related catabolic genes, transporters (black box) and downstream targets. h–i, Heatmap of relative expression of canonical ATF4 ( h ) and PPARα ( i ) target genes in the liver. j , Hepatic Fgf21 expression (log 2 relative to reference genes) in males and females, at P28, P42 and P70. k , Circulating FGF21 concentrations (serum) in males and females, from P28 to P70. Unless otherwise stated, data are mean ± sd; symbols indicate post hoc significance of diet effect (* P □<□0.05, ** P □<□0.01, *** P □<□0.001), ns , not significant. The number of mice used in each panel is provided in Extended Data Table 2 .

Article Snippet: IGF-1 levels were measured with the Mouse/Rat IGF-1 Quantikine ELISA Kit (R&D Systems, #MG100), and FGF21 levels with the Mouse/Rat FGF21 ELISA Kit (BioVendor, #RD291108200R).

Techniques: Expressing

a–f , Postweaning growth indicators in males ( a–c ) and females ( d–f ) fed control (CD) or low-protein diet (LPD) from P21 to P56. Size curves in males ( a ) and females ( d ) from P21 to P56. Effect size (Cohen’s d ) of Fgf21 HepKO vs Fgf21 Hepfl/fl on body length in males ( b ) and females ( e ) over time. Dashed lines represent 95% confidence intervals. Femur length of males ( c ) and females ( f ) at P56. g , Cumulative onset of balano-preputial separation (BPS) in males from P21 to P56. h, Sperm count at P56 in adult males. i, Seminal vesicle weight at P56 plotted against body weight. Dashed line represents the fitted ANCOVA model without interaction (main effects only). j, Testis weight at P56. k, Cumulative onset of vaginal opening (VO) in females from P21 to P56. l, Cumulative onset of first oestrus in females from P21 to P56. m, Uterus weight at P56. Data represent mean□±□sd. Symbols indicate post hoc significance of diet or genotype effect, as highlighted in the figure (* P □<□0.05, ** P □<□0.01, *** P □<□0.001), ns , not significant. Shaded areas ( g, k, l ) represent 95% confidence intervals from Kaplan-Meier survival models. “+” indicates right-censored observations. The number of mice used in each panel is provided in Extended Data Table 2 .

Journal: bioRxiv

Article Title: Liver FGF21 mediates sex-specific adaptation to juvenile protein malnutrition

doi: 10.1101/2025.07.09.663702

Figure Lengend Snippet: a–f , Postweaning growth indicators in males ( a–c ) and females ( d–f ) fed control (CD) or low-protein diet (LPD) from P21 to P56. Size curves in males ( a ) and females ( d ) from P21 to P56. Effect size (Cohen’s d ) of Fgf21 HepKO vs Fgf21 Hepfl/fl on body length in males ( b ) and females ( e ) over time. Dashed lines represent 95% confidence intervals. Femur length of males ( c ) and females ( f ) at P56. g , Cumulative onset of balano-preputial separation (BPS) in males from P21 to P56. h, Sperm count at P56 in adult males. i, Seminal vesicle weight at P56 plotted against body weight. Dashed line represents the fitted ANCOVA model without interaction (main effects only). j, Testis weight at P56. k, Cumulative onset of vaginal opening (VO) in females from P21 to P56. l, Cumulative onset of first oestrus in females from P21 to P56. m, Uterus weight at P56. Data represent mean□±□sd. Symbols indicate post hoc significance of diet or genotype effect, as highlighted in the figure (* P □<□0.05, ** P □<□0.01, *** P □<□0.001), ns , not significant. Shaded areas ( g, k, l ) represent 95% confidence intervals from Kaplan-Meier survival models. “+” indicates right-censored observations. The number of mice used in each panel is provided in Extended Data Table 2 .

Article Snippet: IGF-1 levels were measured with the Mouse/Rat IGF-1 Quantikine ELISA Kit (R&D Systems, #MG100), and FGF21 levels with the Mouse/Rat FGF21 ELISA Kit (BioVendor, #RD291108200R).

Techniques: Control