Then, we demonstrated that leptin challenge failed to reduce appetite of 5 months IUGR rats. Finally we detected anomalies in hypothalamic cellular leptin signals and receptors that could sustain the observed leptin resistance. In human, rapid catch-up growth of low birth weight babies may increase their risk to develop obesity at adulthood. With the use of a now classic animal model of IUGR we demonstrated that rapid catch-up growth after IUGR increase the total fat mass of rats that are fed with standard equilibrated rodent chow. While 5 months old IUGR rats did not yet demonstrate obvious sign of obesity they accumulated higher fat deposits and showed a hypertrophy of the adipocytes. In human and animal models metabolic risks and obesity are correlated with a larger visceral adipose tissue. Similar observation were published on a mouse model of catch-up growth which developed an exacerbated adipose tissue at CT99021 adulthood that even increased when the animals were fed with a high fat diet. Although the RR groups displayed smaller fat pads compared to RC and control group, a previous work of a team of our laboratory showed that they developed higher abdominal fat and a higher increase in serum triglycerides and free fatty levels after exposure to high fat diet than control offspring. Under control chow diet fat mass hypertrophy of the IUGR rats with catch-up growth was associated with a higher expression of leptin mRNA. Additionally in that IUGR rat model we demonstrated plasmatic hyperleptinemia measured shortly after a refeeding period and after high caloric diet intake. Both groups of adult IUGR rats demonstrated an impaired response to leptin challenge since a single peripheral leptin injection did not decrease their food intake nor reduce their weight gain on a 24 h period compared to control rats. Detection of leptin-stimulated pSTAT3 in the hypothalamus by immunoblotting is an other way to evaluate leptin sensitivity level measurement in hypothalamus. However leptin action in the hypothalamus also mediates signalling by STAT5, ERK, PI3 kinase, mTOR, AMPK and potentially other pathways that are completely or partially independent of STAT-3. Additionally they can be influenced by other factors as insulin or amino acid availability which therefore confounds their use as readouts off cellular leptin signalling. Altough it is known that analysis of these pathways are more difficult to detect than pSTAT3, they may be affected in certain metabolic state and deserve examination. With impaired activation of the PI3K/AKT pathway and a hyper stimulation of mTOR pathway. A large body of evidence suggests that leptin signalling through STAT3 is critical for maintaining normal energy homeostasis. However in experimental animals as diet-induced obesity rats and mice although the anorectic effect of central leptin is reduced, the leptin induced STAT3 activation remained intact for 4 to 19 weeks and becomes impaired after the development of DIO and probably contributes to the maintenance of DIO on a high fat diet. Although disruption of the STAT3 binding site in LepRb or deletion of neuronal STAT3 results in severe hyperphagia and morbid obesity, deletion of STAT3 in either POMC or AgRP neurons only slightly increases food intake and adiposity in mice. This implies that other cellular pathway participate to leptin resistance.