Figure 4. Hepatic metabolic responses exhibit a temporal pattern after RYGB.

A. Heat map of mean log₂ fold change in expression levels of genes of differentially regulated metabolic pathways. RYGB-treated vs. WMS mice 9 days (N=4 per group) and 9 weeks (wks; N= 5 for RYGB and N= 4 for WMS) after surgery; and human patients less than 1 year (yr) post-bariatric surgery vs. lean patients, who did not undergo surgery (reanalysis of dataset from (Ahrens et al., 2013)). MM: mus musculus and HS: homo sapiens. Here and in entire figure, genes are sorted by fold change at the 9-day post-RYGB time-point. N.E: no expression was detected.

B. Partial metabolic network for differentially expressed genes related to lipid, glucose and amino acid metabolism (FDR<0.05). RYGB-treated vs. WMS mice. Genes were mapped red or blue if they were up or down-regulated respectively. Regular fonts: 9 days after surgery, bold fonts and within brackets: 9 weeks after surgery.

C. Hematoxylin and Eosin staining of liver sections (N=5 per group). Large lipids droplets (black arrowhead) were prevalent in WMS mice and rare after RYGB. Scale bar=50μm. Quantification of lipid droplet area. * RYGB vs. WMS independent samples t-test, p<0.05.

D. Immunohistochemical staining for PPARα in liver sections (N=5 per group) displaying increased nuclear localization of PPARα after RYGB. Scale bar=50μm, 250μm in expanded panel. Slides were counterstained with hematoxylin.

E. Mean log₂ fold change in expression levels of PPARα target genes that were differentially expressed (FDR<0.05) in RYGB-treated compared to WMS mice at both 9-day and 9-week time-points.

F. Pparα activation score 9 days and 9 weeks after RYGB.

G. Pathway analysis of serum metabolites, measured by HILIC-POS in human patients. Comparison between RYGB-treated patients and controls with obesity (BWH cohort, RYGB N=25, Controls N=12). Many pathways involved in nitrogen metabolism were significantly enriched, suggesting that RYGB induces substantial changes in amino acid metabolism.