RESUMO
BACKGROUND: Perinatal exposure to a poor nutritional environment predisposes the progeny to the development of metabolic disease at the adult age, both in experimental models and humans. Numerous adaptive responses to maternal protein restriction have been reported in metabolic tissues. However, the expression of glucose/fatty acid metabolism-related genes in adipose tissue and liver needs to be described. AIM: To evaluate the metabolic impact of perinatal malnutrition, we determined malnutrition-associated gene expression alterations in liver and adipose tissue. METHODS: In the present study, we evaluated the alterations in gene expression of glycolytic/Krebs cycle genes (Pyruvate dehydrogenase kinase 4 and citrate synthase), adipogenic and lipolytic genes and leptin in the adipose tissue of offspring rats at 30 d and 90 d of age exposed to maternal isocaloric low protein (LP) diet throughout gestation and lactation. We also evaluated, in the livers of the same animals, the same set of genes as well as the gene expression of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1, forkhead box protein O1 and hepatocyte nuclear factor 4 and of gluconeogenic genes. RESULTS: In the adipose tissue, we observed a transitory (i.e., at 30 d) downregulation of pyruvate dehydrogenase kinase 4, citrate synthase and carnitine palmitoyl transferase 1b gene expression. Such transcriptional changes did not persist in adult LP rats (90 d), but we observed a tendency towards a decreased gene expression of leptin (P = 0.052). The liver featured some gene expression alterations comparable to the adipose tissue, such as pyruvate dehydrogenase kinase 4 downregulation at 30 d and displayed other tissue-specific changes, including citrate synthase and fatty acid synthase upregulation, but pyruvate kinase downregulation at 30 d in the LP group and carnitine palmitoyl transferase 1b downregulation at 90 d. These gene alterations, together with previously described changes in gene expression in skeletal muscle, may account for the metabolic adaptations in response to maternal LP diet and highlight the occurrence of persistent transcriptional defects in key metabolic genes that may contribute to the development of metabolic alterations during the adult life as a consequence of perinatal malnutrition. CONCLUSION: We conclude that perinatal malnutrition relays long-lasting transcriptional alterations in metabolically active organs, i.e., liver and adipose tissue.
RESUMO
Systemic arterial hypertension (SAH) is an important risk factor for cardiovascular disease and affects worldwide population. Current environment including life style coupled with genetic programming have been attributed to the rising incidence of hypertension. Besides, environmental conditions during perinatal development such as maternal malnutrition can program changes in the integration among renal, neural, and endocrine system leading to hypertension. This phenomenon is termed phenotypic plasticity and refers to the adjustment of a phenotype in response to environmental stimuli without genetic change, following a novel or unusual input during development. Human and animal studies indicate that fetal exposure to an adverse maternal environment may alter the renal morphology and physiology that contribute to the development of hypertension. Recently, it has been shown that the maternal protein restriction alter the central control of SAH by a mechanism that include respiratory dysfunction and enhanced sympathetic-respiratory coupling at early life, which may contribute to adult hypertension. This review will address the new insights on the maternal diet induced-hypertension that include the potential role of the phenotypic plasticity, specifically the perinatal protein malnutrition, and sympathetic-respiratory overactivity.