Figure 4. Effect of Neonatal Leptin Treatment on Metabolic Programming Caused by Maternal Undernutrition in the Rat.

Female rats were subjected in utero to maternal undernutrition (UN) or ad libitum feeding (AD), treated with saline or leptin between days 3 and 13 of life, and fed a normal diet or a high-fat diet after having been weaned. Panel A shows the diet-induced obesity (defined as the difference in total body weight between rats fed a high-fat diet and those fed a normal diet) at 170 days of age. Neonatal leptin treatment prevented the increased susceptibility to diet-induced obesity associated with a high-fat diet after maternal undernutrition. The P value is for the comparison of the UN group with the other three groups. The expression of hepatic genes (for 11β-hydroxysteroid dehydrogenase type 2 [11β-HSD2], peroxisome proliferator-activated receptor α [PPAR-α], and phosphoenolpyruvate carboxykinase [PEPCK]) (Panel B) and promoter methylation of the PPAR-α gene (Panel C) are shown for female rats at 170 days of age. The data in Panels B and C are means, with T bars indicating SEs, for eight rats per group. The control groups in Panels B and C consisted of female offspring in the AD group, treated with saline and fed a normal diet after weaning. Adapted from Vickers et al.⁷⁷ and Gluckman et al.⁷⁸