•Restrictive and hyperlipidic diets alter dopaminergic gene expression.•Mice dams and their offspring had altered gene expression in ventral tegmental area.•Only mice dams had altered gene expression ...due to diet in hypothalamus.•Locomotor activity of mice dams was increased by restrictive and hyperlipidic diets.•Locomotor activity was correlated with dopaminergic gene expression in mice dams.
The neurocircuitry underlying hunger, satiety, motivation to eat and food reward is complex, however a lot of mechanisms are still unknown. Two main cerebral areas are responsible for controlling feeding through hunger and food reward: the hypothalamus (HPT) and the ventral tegmental area (VTA), respectively. The dopaminergic system modulates both these areas and is essential to control food ingestion. Therefore, we aim to evaluate the effects of restrictive and hyperlipidic diets during pregnancy, lactation and during adult life of the offspring, on the expression of dopaminergic system genes in VTA and HPT of mice dams and their adult male offspring. We also measured diets’ effect in locomotor activity in the open field (OF) test. Female mice were divided into control (CONT), restriction (RD) and hyperlipidic (HD) dietary groups, and mated with isogenic male mice. On the 9th postpartum day (PPD), dams were tested in the OF, and on the 22nd PPD cerebral areas were collected. After weaning, the offspring also were divided into one of three diet groups, independently of the diets provided to their dams. In the 80th PPD, the offspring was tested in the OF, and at 100th PPD, VTA and HPT were collected. Gene expression was analyzed by quantitative reverse transcription real-time polymerase chain reaction. The correlation between gene expression and locomotor activity was also assessed. In dams’ VTA, both diets upregulated the expression of Th, Slc6a3/Dat1, Drd1 and Drd2 genes. In opposition, in the offspring the maternal diet was associated with a reduction in Th and Ddc gene expression. In the HPT, mice dams that received restriction or hyperlipidic diets had increased Th mRNA levels, but reduced the expression of Drd4 gene. The offspring diet had no effect on the expression of the studied genes in their adult lives. Both diets increased mice dam’s locomotion in the OF, however none of them altered the offspring locomotor activity. We detected a positive correlation between the duration of total locomotion in the OF and Slc6a3/Dat1 gene expression in VTA of mice dams. In the HPT, a negative correlation of locomotion and Drd4 mRNA levels, and a positive correlation with Th gene expression was observed. Our results show that restriction and hyperlipidic diets alter mice dams’ locomotor activity in the OF and modify the expression of dopaminergic system genes in VTA and HPT of mice dams and in VTA of the offspring.
Restrictive diets (RD) can influence the inflammatory phenotype of dams and their offspring. Thus, this study aimed to evaluate the effects of caloric restriction on the neuroinflammatory profile in ...the hippocampus and the short-term recognition memory of male offspring from RD-fed dams. Mice dams received standard diet ad libitum (CONT) or restrictive diet (RD; 30% reduction of CONT consumption) during pregnancy and lactation. Male pups were weaned at 21 days and randomly divided into two groups that received CONT or RD; groups were named according to maternal/offspring diets: CONT/CONT, CONT/RD, RD/CONT, and RD/RD. At 90 days old, short-term memory was assessed by the object recognition test (ORT); the inflammatory state of the hippocampus was analyzed by gene expression of sirtuin-1 (Sirt1) and inflammasome Nlrp3; and by protein expression of toll-like receptor-4 (TLR-4) and zonula occludens-1 (ZO-1). Our results showed an improvement in short-term memory in RD-fed offspring. The expression of Sirt1 was higher in RD/CONT compared to CONT/CONT and decreased in RD/RD compared to CONT/RD. Nlrp3 gene expression showed an offspring effect, being decreased in RD-fed mice. TLR-4 expression was higher in RD/CONT compared to CONT/CONT, similarly to ZO-1 expression. However, ZO-1 also showed a maternal diet effect and increased expression in the offspring of RD dams. Our findings demonstrate that caloric restriction improved short-term recognition memory. However, a restrictive diet should be applied with caution; depending on the offspring's diet, it may not benefit the neuroinflammatory phenotype or cognition.
•Caloric restriction, when moderate and early in life, can improve cognition.•Maternal caloric restriction increased expression of Sirt1 in the hippocampus.•Caloric restriction reduces Nlrp3 gene expression in the hippocampus.•Caloric restriction alters TLR-4 expression in the hippocampus of adult offspring.•Restriction diet may protect the blood brain barrier in the adult offspring.
Objective
The purpose of this study was to evaluate the effects of zinc (Zn) supplementation on metabolic and neuroinflammatory parameters in cafeteria diet (CAF)‐induced obesity in Wistar rats.
...Methods
Animals were divided into four groups: control diet (CT); CT+Zn; CAF; CAF+Zn. The diet was administered for 20 weeks; Zn treatment (10 mg/kg/d) started at week 16 and it was conducted until the end of the diet protocol. Weight gain, visceral fat, and plasma levels of glucose, triglycerides, insulin, TNF‐α, and IL‐6, as well as homeostatic model assessment of insulin resistance, were assessed. Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba‐1) expression in the cerebral cortex and toll‐like receptor 4 (TLR‐4) in the cerebral cortex and hippocampus were evaluated. Memory was assessed by the novel object recognition test.
Results
CAF diet increased weight gain, visceral fat, and plasma glucose, triglyceride, and TNF‐α levels. Zn reversed the hyperglycemia caused by CAF diet and reduced IL‐6 levels. In the cerebral cortex, GFAP was similar between groups; Iba‐1 was increased by CAF diet but reduced in the CAF+Zn group. Zn reduced CAF‐dependent TLR‐4 increase in the hippocampus but not in the cerebral cortex. CAF‐fed animals showed impaired recognition memory, whereas Zn reversed it.
Conclusions
These findings demonstrate that Zn partially reverted obesity‐related metabolic dysfunction and reduced neuroinflammation and memory deficit caused by CAF diet.
Genetic and environmental factors related to maternal diet may predispose offspring to serious diseases. However, consequences of a maternal diet intervention during gestation and lactation, and its ...association with caloric restriction after weaning on the progeny are not completely known. In this context, the goal of the present study was to investigate how different maternal diets, control (CONT), hypercaloric (HD) or restrictive (RD) diets during gestation and lactation, may affect the metabolism and behavior of the offspring that was also submitted to RD. Experimental groups were abbreviated accordingly maternal/offspring diets: CONT/CONT, CONT/RD, RD/CONT, RD/RD, HD/CONT, HD/RD. Our results showed that glucose serum concentration is increased in mice from dams fed a HD. However, offspring from RD-fed dams showed lower insulin and leptin levels than the other groups, indicating a maternal diet effect. Moreover, animals from RD/CONT group showed a higher adipocyte area in comparison to both HD/CONT and CON/CONT. Offspring from RD-fed dams exhibited a decrease in lateral area locomotion in the open field test. Evaluation of anxiety-like behavior and recognition memory showed no significant difference among groups. Thus, maternal RD provides a beneficial response in metabolic parameters, but its effects on behavior is not completely clarified.
•Maternal RD exert a protective metabolic effect for offspring in a long-term.•Maternal restrictive diet affects adipocyte area in the adult female offspring.•Offspring from RD-fed dams showed lower insulin and leptin levels.•Offspring of RD-fed dams exhibited decreased locomotion in the lateral area of the open field.
•Dendritic spines in the MePD can be modulated by the deletion of the OT gene.•Number and shape of dendritic spines in the MePD are modulated by sexual experience.•Sexual experience reduced the ...density of proximal dendritic spines in the MePD.•WT and OTKO näive mice did not differ in the density of dendritic spines.
Oxytocin has central actions that modulate synaptic plasticity and the occurrence of social behavior in rodents. The posterodorsal medial amygdala (MePD) composes a sexually dimorphic neural circuit for the display of male sexual behavior. Local dendritic spines are notably plastic and affected by context-dependent social stimuli. Here, we examined the effects of the selective deletion of the OT gene (OTKO) in the number and shape of Golgi-impregnated dendritic spines in the MePD of näive and sexually experienced (SexExp) male mice (n=6 each group). Compared to the control wild-type mice (WT), OTKO näive mice did not differ in the density of dendritic spines, but there was a significant and more intense reduction in the number of spines in the WT/SexExp (∼40%) than in the OTKO/SexExp (∼25%). This structural change had a spine-specific feature. That is, sexual experience induced a decrease in the number of thin (∼50%) and mushroom-like spines (∼35%) at the same time that increased (∼30%) the number of stubby/wide spines. In addition, the OTKO/SexExp animals have more thin and mushroom spines than the WT/SexExp ones (∼25% and 55%, respectively; p <0.01 in all cases). In conjunction, these novel data indicate that OT participates in the spine remodeling, synaptic refinement, and social stimuli-dependent plasticity in the MePD of male mice.
The placenta is an organ that forms the bridge between mother and fetus during pregnancy. Changes in the intrauterine environment directly impact the fetus’ health, with maternal nutrition ...determining its development. This study analyzed the effects of different diets and probiotic supplementation during pregnancy on the biochemical parameters of maternal serum and placental morphology, oxidative stress, and cytokine levels in mice.
Female mice were fed standard (CONT), restrictive (RD), or high-fat (HFD) diets before and during pregnancy. During pregnancy, the CONT and HFD groups were divided into two groups that received the Lactobacillus rhamnosus LB1.5 three times per week (CONT + PROB and HFD + PROB). The RD, CONT, or HFD groups received vehicle control. Maternal serum biochemical parameters (glucose, cholesterol, and triglycerides) were evaluated. The morphology, redox profile (thiobarbituric acid reactive substances, sulfhydryls, catalase, and superoxide dismutase enzyme activity), and inflammatory cytokines (interleukins 1α, 1β, IL-6, and tumor necrosis factor-alpha) were evaluated in the placenta.
The serum biochemical parameters presented no differences between the groups. Regarding placental morphology, the HFD group showed an increased thickness of the labyrinth zone compared to the CONT + PROB group. However, no significant difference was found in the analysis of the placental redox profile and cytokine levels.
RD and HFD, for 16 weeks before and during pregnancy, as well as probiotic supplementation during pregnancy, caused no change in serum biochemical parameters nor the gestational viability rate, placental redox state, and cytokine levels. However, HFD increased the thickness of the placental labyrinth zone.
•High-fat diet increases the thickness of the labyrinth zone in the placenta.•Increased thickness of the placenta may alter transport between mother and fetus.•High-fat and restrictive diets during pregnancy did not alter the placental cytokines.•Gestational viability was not affected by high-fat or restrictive diets.•High-fat and restrictive diets did not alter the redox state in the placenta.
Probiotic supplementation has been identified as a potential target to reduce inflammatory mediators associated with obesity. Therefore, this study assessed the effect of probiotic
LB1.5 on ...anxiety-like behavior, gene expression in the prefrontal cortex, and neuroinflammation in the cerebral cortex and hippocampus of male mice fed a high-fat diet. Mice aged 21 days were divided into four groups: control (CONT), control plus probiotic (CONT + PROB), high-fat diet (HFD), and high-fat diet plus probiotic (HFD + PROB), and fed for 13 weeks. The probiotic
1.5 (3.1 × 108 CFU/mL, derived from raw buffalo milk) was administered by gavage three times a week. Probiotic supplementation provided an anxiolytic effect in CONT and HFD. The IL-6 showed lower levels after probiotic supplementation in the HFD. Regarding immunoreactivity for GFAP in the cerebral cortex, we demonstrated that animals HFD-fed had a reduction in cells number compared to CONT. In the hippocampus, we found an interaction between diet and supplementation, as well as an effect of probiotic supplementation. A higher number of Th positive cells was observed in the cerebral cortex in mice fed HFD.
LB1.5 supplementation decreased serum IL-6 levels in HFD-fed mice and promoted a reduction in anxiety-like behavior.
Maternal diet is key to the progeny’s health since it may impact on the offspring’s adult life. In this study, mice dams received standard (CONT), restrictive (RD), or hypercaloric (HD) diets during ...mating, pregnancy, and lactation. Male offspring of each group of dams also received these diets: CONT, RD, HD. Aiming to evaluate the oxidative stress in the adipose tissue, reactive oxygen species (ROS) production, catalase (CAT), and superoxide dismutase (SOD) activities were analyzed in dams and offspring. In the adipose tissue and hypothalamus, gene expression of prolactin (Prlr) and estrogen alpha (Esr1) receptors was performed in dams and offspring. Protein expression of Stat5 was evaluated in the adipose tissue of the offspring from RD-fed dams. HD-fed dams increased triglycerides and leptin serum concentrations, and decreased SOD activity in the adipose tissue. In the offspring’s adipose tissue, we observed a maternal diet effect caused by HD, with increased ROS production and SOD and CAT activities. Gene expression of Prlr and Esr1 in the offspring’s adipose tissue was decreased due to maternal RD. Mice from HD-fed dams showed higher Stat5 expression compared to the offspring from CONT and RD dams in the adipose tissue. In the hypothalamus, we found decreased expression of Prlr in RD and HD dams, compared to CONT; and a maternal diet effect on Prlr and Esr1 gene expression in the offspring. In conclusion, we can affirm that maternal nutrition impacts the redox state and influences the gene expression of Prlr and Esr1, which are involved in energy metabolism, both peripherally and centrally in the adult life of the female offspring.
Pregnancy and lactation are important stages of fetal development. Therefore, this study investigated how different maternal diets offered during gestation and lactation periods affect adipose tissue ...inflammation and liver tissue oxidative stress of dams and their female offspring. Female BALB/c albino mice (60 days old) were randomized into three groups receiving a standard (CONT), hypercaloric (HD), or restricted (RD) diet during the pregnancy. After birth, female offspring weaned at 21 days were divided into two groups that received a standard or restricted diet (CONT/CONT, CONT/RD, RD/CONT, RD/RD, HD/CONT, and HD/RD) until 100 days old. Histological, oxidative parameters and inflammatory infiltrate of dams’ and offspring’s liver and adipose tissue were evaluated. HD dams presented non-alcoholic steatohepatitis (NASH) diagnosis and an increase in tumor necrosis factor-alpha (TNF-α) concentrations when compared to the RD and CONT dams, indicating a pro-inflammatory state. High concentrations of malondialdehyde (MDA) formation and catalase (CAT) activity in HD when compared to the CONT in the liver. SOD activity decreased in RD mice compared to CONT, and the SOD/CAT ratio was decreased in the RD and HD in comparison to the CONT. The maternal diet leads to an increase in SOD in RD/RD compared to HD/RD. RD-fed dams showed an increase in inflammatory infiltrates compared to CONT, evidencing changes caused by a restrictive diet. In the HD/CONT offspring, we verified an increase in inflammatory infiltrates in relation to the offspring fed a standard diet. In conclusion, HD, and RD, during pregnancy and lactation, altered the liver and adipose tissues of mothers. Furthermore, the maternal diet negatively impacts the offspring’s adipose tissue but does not cause liver damage in these animals in adult life.
Any condition leading to chronic liver disease is a potential oncogenic agent for hepatocellular carcinoma (HCC). Alterations in the expression of antioxidant enzymes could alter the redox balance. ...Our aim was to evaluate the expression of the genes GPX1, GPX4, SEP15, SELENOP, SOD1, SOD2, GSR, CAT, and NFE2L2 in patients with HCC. Differential gene expression analysis was performed using RNA-Seq data from the TCGA and GTEx databases, and RT-qPCR data from HCC patient samples. Bioinformatic analysis revealed significant differential expression in most genes. GPX4 expression was significantly increased (p=0.02), while SOD2 expression was significantly decreased (p=0.04) in experimental data. In TCGA samples, alpha-fetoprotein levels (mg/dL) were negatively correlated with the expression of SEP15 (p<0.001), SELENOP (p<0.001), SOD1 (p<0.001), SOD2 (p<0.001), CAT (p<0.001), and NFE2L2 (p=0.004). Alpha-fetoprotein levels were positively correlated with the expression of GPX4 (p=0.02) and SELENOP (p=0.01) in the experimental data. Low expression of GPX1 (p=0.006), GPX4 (p=0.01), SELENOP (p=0.006), SOD1 (p=0.007), CAT (p<0.001), and NFE2L2 (p<0.001), and higher levels of GSR, were associated with low overall survival at 12 months. These results suggest a significant role for these antioxidant enzymes in HCC pathogenesis and severity.
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