1. Fig. 1. Body growth and leptin responsivity in young CPO and CTR mice
Fig. 1. Body growth and leptin responsivity in young CPO and CTR mice. A, Body weight from P2 to P30. Mice were weaned onto standard chow at P23 (CTR: n = 65, eight litters; CPO: n = 66, 23 litters). B, Body weight gain from P2 to 23 (CTR: n = 65, eight litters; CPO: n = 66, 23 litters). Total fat mass (C), serum leptin levels (D), and serum leptin normalized to total fat mass (E) at 16 d of age (CTR: n = 12, two litters; CPO: n = 10, four litters). F–H, Peripheral leptin-induced pSTAT3-ir in the ARH in CTR (F) and CPO (G) mice at 16 d of age and total pSTAT3-ir-positive cells (H) (CTR: n = 4, three litters; CPO: n = 4, three litters). Results expressed as mean ± sem. **, P < 0.005; ***, P <
From: Early Overnutrition Results in Early-Onset Arcuate Leptin Resistance and Increased Sensitivity to High-Fat Diet
Endocrinology. 2010;151(4): doi: /en
Endocrinology | Copyright © 2010 by The Endocrine Society

2. Fig. 2. Energy and glucose homeostasis in juvenile and adult CPO and CTR mice. A, Mean daily caloric intake of standard chow diet averaged across 7 d, P38–44 (CTR: n = 19, two litters; CPO: n = 15, five litters; ***, P < vs. CTR). B, Mean daily temperature in standard chow-fed mice, averaged across 5 d (P38–44; *, P < 0.05 by repeated measures ANOVA during the lights off period). The thickness of the traces represents the mean ± sem of n = 9/group (two litters for CTR, five for CPO). C, Mean daily activity in standard chow-fed mice, averaged across 5 d (P38–44; traces represent mean ± sem of n = 9/group, from two litters for CTR, 5 for CPO). D, Corresponding mean AUC across 24 h. *, P < E, Leptin effects on food intake (1900 to 0700 h) at 8 wk of age after 2 consecutive days of leptin (2 μg/g body weight, ip, 1900 h) or saline injections, 5 d apart (CTR: n = 9, two litters; CPO n = 9, five litters; *, P < 0.05; **, P < vs. saline). F, Glucose response at 9 wk of age after overnight fast and ip administration of glucose (1 mg/g body weight, 0900 h) (CTR: n = 7, six litters; CPO: n = 7, six litters).
From: Early Overnutrition Results in Early-Onset Arcuate Leptin Resistance and Increased Sensitivity to High-Fat Diet
Endocrinology. 2010;151(4): doi: /en
Endocrinology | Copyright © 2010 by The Endocrine Society

3. Fig. 3. Food intake and energy expenditure in response to acute and chronic HFD exposure. A, Daily caloric intake in CPO and CTR mice fed standard chow (P38–45), 45% HFD (P46–56), or 60% HFD (P57–65). Dotted lines represent mean daily intake of standard chow averaged across P38–45 (CTR: n = 10, two litters; CPO: n = 5, four litters; *, P < 0.01, †, P < 0.05 compared with baseline, t tests). B, Feed efficiency, calculated as a ratio of body weight gain over total caloric intake across 9 d of HFD intake (CTR: n = 9, two litters; CPO: n = 10, five litters; *, P < 0.05). C, Mean daily activity AUC over 9 d of HFD exposure. Day 0 represents the baseline activity and is the mean activity AUC across 5 d on standard chow (CTR: n = 9, two litters; CPO: n = 10, five litters; *, P < 0.05 by t test at each time point). D, Mean temperature during the lights-off period over 9 d of HFD exposure. Day 0 represents the baseline temperature averaged across 5 d on standard chow (CTR: n = 9, two litters; CPO: n = 10, five litters; *, P < 0.05 by t test). E, Body weight from wk 6 to wk 23 of age. Mice were either maintained on standard chow or placed on 45% HFD at 6 wk and then onto 60% HFD at 8 wk of age. (***, P < ; **, P < 0.005; *, P < 0.05 vs. CTR within diet condition, t tests.) Treatment × diet interaction by three-way repeated-measures ANOVA: CPO HFD > CTR HFD > CPO chow > CTR chow, P < ). F, Body weight gain from wk 6 to wk 23 maintained on chow or HFD (significant treatment × diet interaction by two way ANOVA; ***, P < ). CTR chow: n = 25, eight litters; CPO chow: n = 25, 15 litters; CTR HFD: n = 38, eight litters; CPO HFD: n = 38, 16 litters).
From: Early Overnutrition Results in Early-Onset Arcuate Leptin Resistance and Increased Sensitivity to High-Fat Diet
Endocrinology. 2010;151(4): doi: /en
Endocrinology | Copyright © 2010 by The Endocrine Society

4. Fig. 4. Leptin responsivity in response to chronic HFD
Fig. 4. Leptin responsivity in response to chronic HFD. pSTAT3 was quantified in 22-wk-old mice in the ARH (A) and the DMH (B) of the hypothalamus after ip injection of saline or 2 μg/g body weight of leptin. Saline-injected images are from CTR chow mice and did not differ among groups. Total pSTAT3-positive cells in the ARH (C) and DMH (D) (treatment × diet interaction by two way ANOVA: **, P < compared with all other groups) in response to ip injection of saline or 2 μg/g leptin [n per group (one pup per litter): CTR chow saline, three, leptin, three; CPO chow saline three, leptin, four; CTR HFD saline four, leptin six; CPO HFD saline four, leptin five]. E, Forty-eight-hour change in body weight in 22-wk-old mice injected with leptin (ip, 2 μg/g body weight) or saline for 2 consecutive days at 1900 h, 5 d apart (CTR chow: n = 8, four litters; CPO chow: n = 8, five litters; CTR HFD: n = 13, five litters; CPO HFD: n = 18, eight litters; *, P < 0.05 vs. saline).
From: Early Overnutrition Results in Early-Onset Arcuate Leptin Resistance and Increased Sensitivity to High-Fat Diet
Endocrinology. 2010;151(4): doi: /en
Endocrinology | Copyright © 2010 by The Endocrine Society

5. Fig. 5. GTTs and ITTs in response to chronic HFD
Fig. 5. GTTs and ITTs in response to chronic HFD. Glucose response in chow- or HFD-fed mice after ip administration of glucose (1 mg/g) at 15 wk age (A), corresponding AUC from 0 to 120 min, with the glucose level at 0 min considered as the baseline (B), and fasting glucose levels at 0 min (C) (CTR chow: n = 7, seven litters; CPO chow: n = 8, eight litters; CTR HFD: n = 15, eight litters; CPO HFD: n = 12, 12 litters; *, P < 0.05, main effect of diet, two way ANOVA; +, P < 0.05, vs. CTR HFD, t test). D, Plasma insulin at 0 and 60 min during the GTT (CTR CHOW: n = 5, four litters; CPO chow: n = 4, three litters; CTR HFD: n = 6, four litters; CPO HFD: n = 4, three litters; *, P < 0.05 vs. CPO chow, CTR HFD; t tests). Glucose response in 17-wk-old chow- or HFD-fed mice after ip insulin (1 mU/g) (E) and corresponding AUC from 0 to 120 min, with zero considered as the baseline (F) (CTR chow: n = 7, three litters; CPO chow: n = 7, seven litters; CTR HFD: n = 8, four litters; CPO HFD: n = 10, eight litters; *, P < 0.05 vs. all other groups; significant treatment × diet interaction, two-way ANOVA).
From: Early Overnutrition Results in Early-Onset Arcuate Leptin Resistance and Increased Sensitivity to High-Fat Diet
Endocrinology. 2010;151(4): doi: /en
Endocrinology | Copyright © 2010 by The Endocrine Society

6. Fig. 6. Liver histology in response to chronic HFD
Fig. 6. Liver histology in response to chronic HFD. H&E staining (A) and oil red O staining (B) (red, lipid staining) of liver at 6 months of age. C, Liver weight normalized to body weight (CTR CHOW: n = 8, four litters; CPO chow: n = 7, seven litters; CTR HFD: n = 14, four litters; CPO HFD: n = 14, 10 litters; significant treatment × diet interaction: **, P < 0.005, CPO HFD vs. all other groups). D, Degree of hepatic steatosis: mild, isolated regions of steatosis, predominantly macrovesicular; moderate, scattered regions of both macrovesicular and microvesicular steatosis with regions of normal histology; severe, extensive macrovesicular and microvesicular steatosis throughout section. Scale bars, 100 μm.
From: Early Overnutrition Results in Early-Onset Arcuate Leptin Resistance and Increased Sensitivity to High-Fat Diet
Endocrinology. 2010;151(4): doi: /en
Endocrinology | Copyright © 2010 by The Endocrine Society