Restrição protéica materna associada à dieta herlipídica pós-natal altera a estrutura hepática na prole adulta

Abstract

Neonatal protein restriction has been associated with metabolic, structural and morphological adaptations in diverse organs. The type of postnatal diet can further exacerbate these outcomes. The present work aimed at evaluating the effects a postnatal hyperlipidic diet exerts on hepatic morphological parameters of rats subjected to perinatal protein restriction. Virgin female Wistar were divided into 2 groups: normal protein (NP) and low protein (LP). NP dams received standard diet for pregnant rats (AIN-93/Rhoster_- 19% protein) during the whole pregnancy and first half lactation, whereas LP dams had free access to na isocaloric diet lacking the recommended amount of protein (5% protein) for the same period. At weaning, offspring were assigned to one of the 8 nutritional groups according to the diet they will receive (SC standard chow or HF high fat): a) male NP-SC; b) female NP-SC; c) male NP-HF; d) female NP-HF; e) male LPSC; f) female LP-SC; g) male LP-HF e h) fêmea RP-ADE. Body mass and blood pressure were measured weekly until 6 months, when euthanasia occurred. Liver was carefully dissected and had its volume determined through Scherle s method. Analysis of variance (ANOVA) and post-hoc test of Bonferroni were used to test differences among the groups (p<0,05). The HF diet provoked overweight in NP-HF groups from both genders on day 77 (p<0,001). However, LP-HFC groups showed a delayed response and sexual dimorphism, as only females developed overweight on day 112 (p<0,05). As for hepatic alterations, protein restriction resulted in hepatocyte deficit in both genders (p<0.01), existing an additional shift from HF diet exclusively in males (p<0.01). Furthermore, higher steatosis rates were found in protein restricted animals (Vv = 15%, p<0.01), having the post-weaning HF diet an additional effect on this outcome in LP-HF (Vv > 33%, p<0.001). Fetal programming and HF diet as single stimulus caused mild hypertension at 3 months, an important reduction in hepatocyte number as well as stage 1 steatosis at 6 months. However, when both stimuli were applied simultaneously, hypertension and hepatocyte number deficit were worsened and grade 2 steatosis occurred. All of these serve to highlight the paramount importance of intrauterine conditions and postnatal diet quality when it comes to the pathogenesis of chronic diseases.