Sympathetic innervation in both the inguinal and retroperitoneal depot was determined by assessing tissue staining for TH, which is the rate-limiting enzyme for catecholamine synthesis. Of interest, in CR males, SCH772984 noradrenergic innervation of iWAT, but not in rWAT, was significantly reduced at early life, so the adrenergic drive to the subcutaneus depot may be deficient, a situation that could resemble partial Vorinostat dennervation and could hence explain the development of hyperplasia in iWAT in adult CR males. The idea of partial dennervation is not as strange if we consider previous studies showing that 50% undernutrition during the last two weeks of pregnancy can reduce the number of prevertebral sympathetic neurons, and also reduce the enteric sympathetic innervation in the offspring. Moreover, other studies have shown that a protein deficient diet during gestation and after produces atrophy and neuron loss in sympathetic ganglion neurons of rat offspring. Thus, it is feasible that caloric restriction during gestation could lead to partial noradrenergic dennervation of the inguinal adipose tissue and therefore favour the hyperplasia seen in this fat depot in adulthood; however more functional studies could be performed to fully demonstrate a true impairment in sympathetic regulation. In adulthood, at the age of 6 months, noradrenergic innervation of iWAT of CR males was also reduced, but this alteration also occurred in the rpWAT. Nevertheless, in the latter, this may be attributed to the increased size of adipocytes, since the decrease was not significant when TH + was referred to the adipocyte number. However, it must be mentioned that since at 6 months of age these animals were under HF diet, it is difficult to distinguish whether the reduced noradrenergic innervation is only a consequence of maternal caloric restriction or it is also an interaction of this condition with HF diet exposure and even with the effects of age. Unlike males, changes in SNS innervation in iWAT or rWAT were not apparent in female animals, neither were there changes in fat accumulation in these depots, as mentioned above, even under conditions that promote body fat accretion. Thus, female animals seem to be more resistant to the negative effects associated to caloric restriction during gestation, as previously described. Female rats have also been described to be more resistant to obesity-linked disorders associated to HF diet exposure. To substantiate the results obtained for TH, we also performed immunohistochemical analysis for NPY in both adipose tissue depots, since this peptide is known to be colocalized with NE and released together with NE upon sympathetic activation. Results concerning NPY + were very similar to those obtained for TH, evidencing a decrease in sympathetic innervation in the iWAT of CR male animals but not in the rpWAT.