Energy homeostasis is affected by changes in nutrition during lactation in male mice with IUGR. (A) Blood glucose concentration during an intraperitoneal glucose tolerance test (ipGTT) in the male (M) young adult (3-month-old mice, left panels, n = 7–12 per group) or old (12-month-old mice, right panels, n = 5–9 per group) control (dashed line), IUGR-R (blue line), IUGR-N (green line), and IUGR-O (red line) mice. The calculation of the area under the curve (AUC) for the young males showed differences between the IUGR-R and IUGR-N/IUGR-O mice. No significant differences in AUC values were observed in the older males. (B) Percent decrease in the glucose levels during an insulin tolerance test (ITT) in the male young adult (3 months old, left panels, n = 9–12 per group) or old (12 months old, right panels, n = 6–10 per group) control, IUGR-R, IUGR-N, and IUGR-O mice. The area above the curve (AAC) indicates better insulin sensitivity in the 3-month-old male IUGR-R mice, an effect that persisted at 12 months of age. Conversely, lower insulin sensitivity was observed in the IUGR-O mice at 3 months, which persisted at 12 months of age. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 for the control vs IUGR, with statistical significance reported with the following comparison symbols Δ: IUGR-O vs IUGR-R, o: IUGR-O vs IUGR-N, and ◊: IUGR-N vs IUGR-R. The corresponding results for the females are shown in Supplementary Figure S4. (C) Representative photomicrographs of Oil Red O-stained sections of livers from the male 3-month-old control, IUGR-R, IUGR-N, and IUGR-O mice (scale bar, 200 μm), with a higher magnification shown in the inset. Quantifications (right panel) indicated a stronger accumulation of lipids in the IUGR-N and IUGR-O mice than in the control and IUGR-R mice (n = 4 per group). (D) Hepatic triacylglycerol (TAG) (left panel), diacylglycerol (DAG) (middle panel), and total ceramide (right panel) contents were determined in the 3-month-old male mice by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The TAG levels were higher in the IUGR-N and IUGR-O mice than in the control and IUGR-R mice, whereas DAG and total ceramide contents were higher in the male IUGR-O mice than in the male IUGR-N and control mice. (E) Representative immunoblots of Ser473-phosphorylated AKT (p-AKT), total AKT, and β-actin in the livers of the 3-month-old male mice after saline (Sal) or insulin (Ins) injections (left panel). The increase in the p-AKT/AKT ratio (normalized against β-actin) in the insulin-stimulated mice compared to the saline-injected mice was lower in the IUGR-N and IUGR-O mice than in the control and IUGR-R mice (n = 6–7 blots per group) (middle panel). The total AKT protein content of the liver was lower in the 3-month-old IUGR-N and IUGR-O mice after saline injections than in the control mice (n = 5–8 blots per group) (right panel). ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 between groups.