Mitochondrial bioenergetics and oxidative status disruption in brainstem of weaned rats: Immediate response to maternal protein restriction.
Mitochondrial bioenergetics dysfunction has been postulated as an important mechanism associated to a number of cardiovascular diseases in adulthood. One of the hypotheses is that this is caused by the metabolic challenge generated by the mismatch between prenatal predicted and postnatal reality. Perinatal low-protein diet produces several effects that are manifested in the adult animal, including altered sympathetic tone, increased arterial blood pressure and oxidative stress in the brainstem. The majority of the studies related to nutritional programming postulates that the increased risk levels for non-communicable diseases are associated with the incompatibility between prenatal and postnatal environment. However, little is known about the immediate effects of maternal protein restriction on the offspring's brainstem. The present study aimed to test the hypothesis that a maternal low-protein diet causes tissue damage immediately after exposure to the nutritional insult that can be assessed in the brainstem of weaned offspring. In this regard, a series of assays was conducted to measure the mitochondrial bioenergetics and oxidative stress biomarkers in the brainstem, which is the brain structure responsible for the autonomic cardiovascular control. Pregnant Wistar rats were fed ad libitum with normoprotein (NP; 17% casein) or low-protein (LP; 8% casein) diet throughout pregnancy and lactation periods. At weaning, the male offsprings were euthanized and the brainstem was quickly removed to assess the mitochondria function, reactive oxygen species (ROS) production, mitochondrial membrane electric potential (ΔΨm), oxidative biomarkers, antioxidant defense and redox status. Our data demonstrated that perinatal LP diet induces an immediate mitochondrial dysfunction. Furthermore, the protein restriction induced a marked increase in ROS production, with a decrease in antioxidant defense and redox status. Altogether, our findings suggest that LP-fed animals may be at a higher risk for oxidative metabolism impairment throughout life than NP-fed rats, due to the immediate disruption of the mitochondrial bioenergetics and oxidative status caused by the LP diet.
Neuropsychiatry and Behavioral Science Graduate Program, Federal University of Pernambuco, 50670-901, Brazil; Laboratory of Biochemistry and Exercise Biochemistry, Department of Physical Education and Sports Science, Federal University of Pernambuco-CAV, Vitória de Santo Antão 55608-680, Brazil.
Diorginis José Soares
DJS
Ferreira
Laboratory of Biochemistry and Exercise Biochemistry, Department of Physical Education and Sports Science, Federal University of Pernambuco-CAV, Vitória de Santo Antão 55608-680, Brazil.
Anderson Apolônio
AA
da Silva Pedroza
Laboratory of Biochemistry and Exercise Biochemistry, Department of Physical Education and Sports Science, Federal University of Pernambuco-CAV, Vitória de Santo Antão 55608-680, Brazil.
Glauber Ruda Feitoza
GRF
Braz
Laboratory of Biochemistry and Exercise Biochemistry, Department of Physical Education and Sports Science, Federal University of Pernambuco-CAV, Vitória de Santo Antão 55608-680, Brazil.
Reginaldo Correia
RC
da Silva-Filho
Laboratory of Biochemistry and Exercise Biochemistry, Department of Physical Education and Sports Science, Federal University of Pernambuco-CAV, Vitória de Santo Antão 55608-680, Brazil.
Talitta Arruda
TA
Lima
Laboratory of Biochemistry and Exercise Biochemistry, Department of Physical Education and Sports Science, Federal University of Pernambuco-CAV, Vitória de Santo Antão 55608-680, Brazil.
Mariana Pinheiro
MP
Fernandes
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Sonia Q
SQ
Doi
Neuropsychiatry and Behavioral Science Graduate Program, Federal University of Pernambuco, 50670-901, Brazil; Laboratory of Biochemistry and Exercise Biochemistry, Department of Physical Education and Sports Science, Federal University of Pernambuco-CAV, Vitória de Santo Antão 55608-680, Brazil. Electronic address: lagranha@hotmail.com.
Claudia Jacques
CJ
Lagranha
D000818:Animals; D001933:Brain Stem / Q000254:growth & development* / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D007774:Lactation; D008297:Male; D044342:Malnutrition / Q000378:metabolism*; D039382:Maternal Nutritional Physiological Phenomena; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014886:Weaning
D017382:Reactive Oxygen Species; D002950:Citrate (si)-Synthase
Brainstem; Mitochondria; Oxidative stress; Rats; Undernutrition