Moderate aerobic training counterbalances the deleterious effect of undernutrition on oxidative balance and mitochondrial markers.

The state of Maternal Protein Malnutrition (MPM) is associated with several deleterious effects, including inflammatory processes and dysregulation in oxidative balance, which can promote neurodegeneration. On the other hand, it is known that aerobic exercise can promote systemic health benefits, combating numerous chronic diseases. Therefore, we evaluate the effect of aerobic exercise training (AET) on indicators of mitochondrial bioenergetics, oxidative balance, endoplasmic reticulum stress, and neurotrophic factor in the prefrontal cortex of malnourished juvenile Wistar rats. Pregnant Wistar rats were fed with a diet containing 17% or 8% casein during pregnancy and lactation. At 30 days of life, male offspring were divided into 4 groups: Low-Protein Control (LS), Low-Protein Trained (LT), Normoprotein Control (NS), and Normoprotein Trained (NT). The trained groups performed an AET for 4 weeks, 5 days a week, 1 h a day per session. At 60 days of life, the animals were sacrificed and the skeletal muscle, and prefrontal cortex (PFC) were removed to evaluate the oxidative metabolism markers and gene expression of ATF-6, GRP78, PERK and BDNF. Our results showed that MPM impairs oxidative metabolism associated with higher oxidative and reticulum stress. However, AET restored the levels of indicators of mitochondrial bioenergetics, in addition to promoting resilience to cellular stress. AET at moderate intensity for 4 weeks in young Wistar rats can act as a non-pharmacological intervention in fighting against the deleterious effects of a protein-restricted maternal diet.

Effects of aerobic exercise training in oxidative metabolism and mitochondrial biogenesis markers on prefrontal cortex in obese mice.

BACKGROUND: To evaluate the effects of 8 weeks of Aerobic Physical Training (AET) on the mitochondrial biogenesis and oxidative balance in the Prefrontal Cortex (PFC) of leptin deficiency-induced obese mice (ob/ob mice). METHODS: Then, the mice were submitted to an 8-week protocol of aerobic physical training (AET) at moderate intensity (60% of the maximum running speed). In the oxidative stress, we analyzed Malonaldehyde (MDA) and Carbonyls, the enzymatic activity of Superoxide Dismutase (SOD), Catalase (CAT) and Glutathione S Transferase (GST), non-enzymatic antioxidant system: reduced glutathione (GSH), and Total thiols. Additionally, we evaluated the gene expression of PGC-1α SIRT-1, and ATP5A related to mitochondrial biogenesis and function. RESULTS: In our study, we did not observe a significant difference in MDA (p = 0.2855), Carbonyl's (p = 0.2246), SOD (p = 0.1595), and CAT (p = 0.6882) activity. However, the activity of GST (p = 0.04), the levels of GSH (p = 0.001), and Thiols (p = 0.02) were increased after 8 weeks of AET. Additionally, there were high levels of PGC-1α (p = 0.01), SIRT-1 (p = 0.009), and ATP5A (p = 0.01) gene expression after AET in comparison with the sedentary group. CONCLUSIONS: AET for eight weeks can improve antioxidant defense and increase the expression of PGC-1α, SIRT-1, and ATP5A in PFC of ob/ob mice.

Overfeeding during development induces temporally-dependent changes in areas controlling food intake in the brains of male Wistar rats.

AIMS: We sought to evaluate the effects of overfeeding during lactation on the feeding behavior and expression of specific regulatory genes in brain areas associated with food intake in 22- and 60-day old male rats. METHODS: We evaluated body weight, food intake of standard and palatable diet, and mRNA expression of dopamine receptor D1 (DDR1), dopamine receptor (DDR2), melanocortin 4 receptor (MC4R), the µ-opioid receptor (MOR), neuropeptide Y (NPY), agouti-related protein (AGRP), proopiomelanocortin (POMC), cocaine-and amphetamine-regulated transcript (CART), serotonin (5-hydroxytryptamine; 5-HT) transporter (SERT), 5-hydroxytryptamine receptor 1B (5-HT1B), 5-hydroxytryptamine receptor 2C receptor (5-HT2C), Clock (CLOK), cryptochrome protein 1 (Cry1) and period circadian protein homolog 2 (Per2) in the striatum, hypothalamus and brainstem of male rats at post-natal days (PND) 22 and 60. KEY FINDINGS: Overfeeding resulted in significantly increased body weight through PND60, and a 2-fold increase in palatable food intake at PND22, but not at PND60. We observed significant increases in DDR1, DDR2, and MC4R gene expression in the striatum and brainstem and POMC/CART in the hypothalamus of the OF group at PND22 that were reversed by PND60. Hypothalamic levels of 5-HT1B, 5-HT2C and NPY/AGRP on the other hand were decreased at PND22 and increased at PND60 in OF animals. Clock genes were unaffected by OF at PND22, but were significantly elevated at PND60. SIGNIFICANCE: Overfeeding during early development of the rat brain results in obesity and altered feeding behavior in early adulthood. The altered behavior might be the consequence of the changes in food intake and reward gene expression.

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.

Can fish oil supplementation and physical training improve oxidative metabolism in aged rat hearts?

AIMS: It is well known that in the aging process a variety of physiological functions such as cardiac physiology and energy metabolism decline. Imbalance in production and elimination of reactive oxygen species (ROS) may induce oxidative stress. Research shows that oxidative stress is an important factor in the aging process. Studies suggest that É·-3 polyunsaturated fatty acids (PUFAs) and moderate physical exercise modulate the ROS system. Therefore, the present study aimed to investigate whether É·-3 present in fish oil supplementation coupled with moderate physical training could improve antioxidant and metabolic enzymes in the hearts of adult and aged rats and, if these effects could be associated to glycemia, plasma lipid profile or murinometric parameters. MAIN METHODS: Adult (weighing 315.1±9.3g) and aged rats (weighing 444.5±11.8g) exercised and receive fish oil supplementation for 4weeks. Then they were used to evaluate murinometric parameters, fasting glucose and lipid profile. After this, their hearts were collected to measure the levels of malondialdehyde (MDA), antioxidant enzyme activity (superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase-GPx) and oxidative metabolism marker (citrate synthase-CS activity). KEY FINDINGS: Fish oil supplementation increases HDL concentration and activity of CAT and CS. Moreover, physical training coupled with fish oil supplementation induces additional effects on SOD, GPx and CS activity mainly in aged rats. SIGNIFICANCE: Our data suggest that combined treatment in aged rat hearts improves the antioxidant capacities and metabolic enzyme that can prevent the deleterious effects of aging.