Figure 2. Fenretinide inhibits Fgf21 expression and improves glucose homeostasis without preventing weight gain in Lepr^db genetically obese mice.

(a) Body weight of C57BL/6 lean mice on chow (lean, n = 8; error bars too small to be shown clearly) and C57BL/6 Lepr^dbmice on 10% fat (Lepr^db, n = 7) or 10% fat diet +FEN (FEN-Lepr^db, = 7). (b) Glucose (1 mg/g body weight) Tolerance Test (GTT) and (c) AUC at week 4. (d) serum insulin levels at the end of the study, following a 5 h fast. (e) Representative photos of haematoxylin and eosin staining of pancreas sections (10x magnification) and quantification of pancreatic islet size (n = 3 per group). (f) Hepatic gene expression and serum levels of FGF21. Gene expression was normalised to Nono. (g) PG-WAT gene expression, normalised to yWhaz. Significant differences were determined by one-way ANOVA followed by post-hoc tests or student’s t-test for PG-WAT Fgf21 FEN-Lepr^db vs Lepr^db and Lepr^db vs lean groups and β-klotho FEN-Lepr^db vs Lepr^db and Lepr^db vs lean groups. Differences are marked *p < 0.05 vs lean or ^#p < 0.05 vs Lepr^db. Quantification of ceramide (h) and dihydroceramide (i) species in liver. (j) Total liver levels of ceramide, dihydroceramide and the dihydroceramide/ceramide ratio. Significant differences were determined by one-way ANOVA followed by post-hoc tests or student’s t-test for ceramides: C18:0 FEN-Lepr^db vs Lepr^db and FEN-Lepr^db vs lean groups, C20:0 FEN-Lepr^db vs Lepr^db and FEN-Lepr^db vs lean groups, C24:1 FEN-Lepr^db vs Lepr^db groups; dihydroceramides: C16:0 FEN-Lepr^db vs Lepr^db and Lepr^db vs lean groups, C18:0 FEN-Lepr^db vs Lepr^db and Leprdb vs lean groups, C20:1 FEN-Lepr^db vs Lepr^db groups, C20:0 Lepr^db vs lean groups, C24:0 FEN-Lepr^db vs lean and Lepr^dbvs lean groups. Differences are marked *p < 0.05 vs lean or ^#p < 0.05 vs Lepr^db.