Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos

Abstract

Environmental and nutritional disorders during the perinatal period cause metabolic dysfunction in the progeny and impairs health through epigenetic programming, which is observable in the small litter (SL) experimental model. Therefore, severe caloric restriction has the potential of affecting several organic systems through the same epigenetic mechanisms, and its effects need elucidation. The objective of this work was to determine whether the food restriction would impact behavioral and cardiovascular parameters in obese and non-obese animals, and the implications to the renin-angiotensin system (RAS) as well as MAPK/ERK in these animals’ hearts. Three days after delivery, female Wistar rats were separated in small litter (SL, 3 pups) and normal litter (NL, 9 pups) groups, their offspring in turn were subjected to food restriction (50%), while another group had free access to chow during the puberty period (from 30 to 60 days). These animals were then subjected to non-anaesthetized recording for the evaluation of cardiovascular parameters, open field (OF), elevated plus maze (EPM) and forced swimming (FS) tests for behavioural analysis. In addition, their body weight and food intake were monitored throughout the experimental period. Finally, the animals were anesthetized, euthanized and had their organs harvested, weighted and preserved for subsequent histological and western blot analysis. SL and SLR offspring were overweight (p<0.05), developing the obese phenotype, observable through increased deposits of white adipose tissue (p<0.05). Differences in mean arterial pressure were also observed, when comparing small litter control animals with the rest of the groups (p<0.05). In addition, SL and SLR offspring showed a tendency for anxiety-like behaviour during the OF test, considering immobility time (p<0.05), and EPM tests considering the number of entries into the open arms (p<0.05). Cardiac remodelling in the NLR and SLR groups was also observed, through the presence of interstitial and perivascular fibrosis (p<0.05), as well as higher expressions of the receptors AT1 and AT2, and of the proteins ERK and p-ERK (p<0.05). The present study shows that early overnutrition caused obesity, anxiety-like behaviours and increases to blood pressure. Also, the animals which underwent food restriction showed no improvement in the behavioural tests, however the non-obese animals subjected to the diet showed similar impairments in behaviour, and for the first time it was shown that severe food restriction caused cardiac remodelling, suggesting that severe food restriction during puberty is capable of causing metabolic programming, negatively impacting these animals later in adult life.