Independently Desai et al. also observed a reduction of leptin activated STAT3 pathway at PND1 after nursing IUGR pups by ad libitum fed dams in order to induce a rapid catch-up growth. These and other findings of the literature reveal the important role of nutrition during the perinatal period in adverse adult health outcomes and permanent changes in energy homeostasis. Leptin is the primary adipose hormones which is produced in proportion to fat stores and circulates as a 16-kDa protein. Adipocytes size is an important determinant of leptin synthesis, since larger adipocytes contain more leptin than smaller. A lack of leptin signalling due to INCB18424 JAK inhibitor mutation of leptin or the leptin receptor in mice and in humans results in an increase of food intake concomitant with a reduction of energy expenditure and leads to severe obesity. Leptin binds to the long form leptin receptor predominantly localized in first order neurons of the arcuate nucleus and in the second order neurons of ventromedial, dorsomedial and paraventricular hypothalamic nuclei. Leptin acts on ARC neurons, stimulates both POMC expression and neuronal excitability and inhibits AgRP/NPY expression and AgRP neuronal excitability. Activation of the LepRb results in the phosphorylation of tyrosine residues on JAK2 and three tyrosines on LepRb. Phosphorylation of LepRb Tyr1138 leads to the phosphorylation, dimerization and nuclear translocation of the signal transducer and activator of transcription which activates the transcription of the suppressor of cytokine signaling-3. SOCS-3 then binds to Tyr985 of LepRb and inhibits its activity. The tyrosine phosphatase, SHP2, also binds LepRb on Tyr985 and activates the MAPK cascade via the extracellular signal-regulated kinase. Leptin also activates phosphatidylinositol3-kinase pathway and mammalian target of rapamycin via AKT. In numerous model of diet induced obesity, the impairment of central leptin signalling mostly in hypothalamic neurons but the mechanisms of leptin resistance remains complex and incompletely understood. Several mechanisms may occur and it is likely that, depending on individual circumstances and types of environment as diet or neonatal exposure, leptin could differentially fail to activate or utilize specific signalling cascade to fulfil its role in energy homeostasis. The main mechanisms of leptin resistance are leptin failure to cross the blood–brain barrier because a downregulation of leptin transporter, hypothalamic LepRb downregulation or abnormalities in the leptin receptor signalling pathways, as inhibition of the JAK2– STAT3 pathway, overexpression of SOCS-3 impairment of PI3K-mTOR pathway or more recently of the ERK pathway. In this study we analyzed what are the potential reasons of metabolic abnormalities experienced by IUGR rats. Therefore we tested central leptin sensitivity in adult rats. Correlation with adipose tissue morphology, fat depots accumulation and leptin synthesis were also recorded. We previously demonstrated that IUGR leads to food behaviour disorders paired with a strong increase of insulin and leptin secretion after a meal. Since hyperleptinemia is a sign of leptin resistance, we hypothesized that an adverse foetal and/or postnatal nutritional environment will program the development of leptin resistance at adulthood.