Glycemic regulation in mice from control (CD, open circles), HFHSD (filed triangles) and reversed (open triangles) groups at baseline and after 1, 2, 4, 8, 16 and 24 weeks of the treatment. Glucose clearance (A) in a glucose tolerance test (GTT) was reduced by HFHSD feeding, as evidenced by both increased area under the curve (AUC) of the GTT (B) and increased glycemia 2 hours after the glucose bolus (C). Blood glucose (D), plasma insulin (E) and HOMA-IR (F) after a 6-hour fasting period indicate insulin resistance in HFHSD-fed male mice. Compared to controls, plasma leptin was increased in HFHSD-fed mice and normalized by diet reversal (G). Data is mean±SD. Letters over data-points indicate significant differences relative to CD or as indicated (a P<0.05, b P<0.01, c P<0.001) based on Fisher’s LSD post hoc comparison following presence of significant effects of diet or interaction between diet and time in ANOVA tests.