Supplementation with Jatobá-do-cerrado flour (Hymenaea stigonocarpa Mart.) decreases hypothalamic inflammation and improves obesity parameters in rats on a high-fat diet.

To evaluate the impact of jatobá-do-cerrado flour on nutritional, inflammatory, and oxidative stress markers, an study was conducted using male Wistar rats. These animals were allocated into four groups: a standard diet (Control), a high-fat diet (HFD), a diet with jatobá-do-cerrado flour (JCF), and a combination of high-fat diet and jatobá-do-cerrado flour (HFD + JCF). Comprehensive evaluations included food intake, cytokine concentrations, and redox status indicators. HFD group exhibited increased caloric intake and fat mass, elevated circulating IL-6, and heightened lipid peroxidation markers. This group also showed increased hypothalamic concentrations of IL-6, TNFα, and lipid peroxidation. In contrast, the HFD + JCF group showed reduced caloric intake, fat mass, and improvements in redox balance and inflammatory markers both in the blood and hypothalamus. SUMMARY: In the current study, we evaluated the potential of Jatobá-do-cerrado flour in mitigating the effects of a high-fat diet in adult Wistar rats. The addition of fat to the animals' diet for 63 days induced obesity, dyslipidemia, as well as an increase in inflammatory and lipid peroxidation markers, both in the blood and hypothalamus. Conversely, supplementation with Jatobá-do-Cerrado flour showed anti-obesogenic effects and these may be associated with the reduction of inflammation and oxidative stress. Therefore, supplementation with this flour has the potential to be a functional food for the treatment or prevention of obesity.

High-intensity interval training improves long-term memory and increases hippocampal antioxidant activity and BDNF levels in ovariectomized Wistar rats.

Menopause is the period in which women cease to produce the hormone estrogen, which can trigger physiological, cognitive, and behavioral changes. In this context, alternatives are needed that can reduce the effects provided by menopause, specifically in terms of cognitive and behavioral aspects. High-intensity interval training (HIIT) is an exercise protocol that has shown the potential to improve cognition by promoting an increase in antioxidant defenses and BDNF levels. Therefore, the aim of this study was to evaluate the effects of HIIT on behavior and hippocampal neurochemistry in ovariectomized adult rats. Four groups of rats were divided into: females without ovariectomy surgery and sedentary (SHAM-SED); females with ovariectomy surgery and sedentary (OVX-SED); females without ovariectomy surgery and trained (SHAM-HIIT); females with ovariectomy surgery and trained (OVX-HIIT). After the surgical procedure and the HIIT protocol, the animals underwent anxiety (elevated plus maze and open field) and memory (novel object recognition) tests. Corticosterone was measured in blood and BDNF levels and redox status were evaluated in the hippocampus. The OVX-SED group showed low BDNF levels and antioxidant enzymes, which may be linked to the observed memory impairments. The HIIT protocol (SHAM-HIIT and OVX-HIIT groups) increased the BDNF levels and antioxidant enzymes in the hippocampus, improving the animals' memory. However, HIIT also led to increased plasma corticosterone and anxiety-like behaviors. The ovariectomy procedure induced memory impairment probably due to reductions in hippocampal BDNF levels and redox imbalance. The HIIT protocol demonstrates promising results as an alternative to improve memory in ovariectomized rats.

COVID-19: Understanding the impact of anti-hypertensive drugs and hydroxychloroquine on the ACE1 and ACE2 in lung and adipose tissue in SHR and WKY rats.

Hypertensive individuals taking anti-hypertensive drugs from renin-angiotensin system inhibitors may exhibit a more severe evolution of the disease when contracting the SARS-CoV-2 virus (COVID-19 disease) due to potential increases in ACE2 expression. The study investigated ACE1 and ACE2 axes and hydroxychloroquine in the lungs and adipose tissue of male and female normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs). SHRs were treated with losartan (10 mg/kg/day) or captopril (10 mg/kg/day) for 14 days or 7 days with hydroxychloroquine (200 mg/kg/day) in drinking water. WKY rats were also treated for 7 days with hydroxychloroquine. Blood pressure (BP), protein, and mRNA expression of ACE1 and ACE2 were analyzed in serum, adipose, and lung tissues. Losartan and captopril reduced BP in both sexes in SHR, whereas hydroxychloroquine increased BP in WKY rats. Losartan reduced ACE2 in serum and lungs in both sexes and in adipose tissue of male SHRs. Captopril decreased ACE2 protein in the lung of females and in adipose tissue in both sexes of SHRs. Hydroxychloroquine decreased ACE1 and ACE2 proteins in the lungs in both sexes and adipose tissue in male SHRs. In female WKY rats, ACE2 protein was lower only in the lungs and adipose tissue. Losartan effectively inhibited ACE2 in male and captopril in female SHRs. Hydroxychloroquine inhibited ACE2 in male SHRs and female WKY rats. These results further our understanding of the ACE2 mechanism in patients under renin-angiotensin anti-hypertensive therapy and in many trials using hydroxychloroquine for COVID-19 treatment and potential sex differences in response to drug treatment.

Aerobic Exercise Training Reduces Atherogenesis Induced by Low-Sodium Diet in LDL Receptor Knockout Mice.

This study investigated the efficacy of aerobic exercise training (AET) in the prevention of dyslipidemia, insulin resistance (IR), and atherogenesis induced by severe low-sodium (LS) diet. LDL receptor knockout (LDLR KO) mice were fed a low-sodium (LS) (0.15% NaCl) or normal-sodium (NS; 1.27% NaCl) diet, submitted to AET in a treadmill, 5 times/week, 60 min/day, 15 m/min, for 90 days, or kept sedentary. Blood pressure (BP), plasma total cholesterol (TC) and triglyceride (TG) concentrations, lipoprotein profile, and insulin sensitivity were evaluated at the end of the AET protocol. Lipid infiltration, angiotensin II type 1 receptor (AT1), receptor for advanced glycation end products (RAGE), carboxymethyllysine (CML), and 4-hydroxynonenal (4-HNE) contents as well as gene expression were determined in the brachiocephalic trunk. BP and TC and gene expression were similar among groups. Compared to the NS diet, the LS diet increased vascular lipid infiltration, CML, RAGE, 4-HNE, plasma TG, LDL-cholesterol, and VLDL-TG. Conversely, the LS diet reduced vascular AT1 receptor, insulin sensitivity, HDL-cholesterol, and HDL-TG. AET prevented arterial lipid infiltration; increases in CML, RAGE, and 4-HNE contents; and reduced AT1 levels and improved LS-induced peripheral IR. The current study showed that AET counteracted the deleterious effects of chronic LS diet in an atherogenesis-prone model by ameliorating peripheral IR, lipid infiltration, CML, RAGE, 4-HNE, and AT1 receptor in the intima-media of the brachiocephalic trunk. These events occurred independently of the amelioration of plasma-lipid profile, which was negatively affected by the severe dietary-sodium restriction.

LPS tolerance prevents anxiety-like behavior and amygdala inflammation of high-fat-fed dams' adolescent offspring.

Maternal high-fat diets (HFD) can generate inflammation in the offspring's amygdala, which can lead to anxiety-like behaviors. Conversely, lipopolysaccharide (LPS) tolerance can reduce neuroinflammation in the offspring caused by maternal high-fat diets. This study evaluated the combination of LPS tolerance and high-fat maternal diet on amygdala's inflammatory parameters and the anxiety-like behavior in adolescent offspring. Female pregnant Wistar rats received randomly a standard diet or a high-fat diet during gestation and lactation. On gestation days 8, 10, and 12, half of the females in each group were intraperitonially injected with LPS (0.1 mg.kg-1). After weaning, the male offspring (n = 96) were placed in individual boxes in standard conditions, and when 6 weeks-old, the animals underwent: Open-Field, Light/Dark Box, Elevated Plus-Maze, and Rotarod tests. When 50 days-old the offspring were euthanized and the amygdala removed for cytokine and redox status analysis. The offspring in the HFD group showed lower amygdala IL-10 levels, high IL-6/IL-10 ratio, and anxiety-like behaviors. These effects were attenuated in the HFD offspring submitted to LPS tolerance, which showed an anti-inflammatory compensatory response in the amygdala. Also, this group showed a higher activity of the enzyme catalase in the amygdala. In addition, receiving the combination of LPS tolerance and maternal HFD did not lead to anxiety-like behavior in the offspring. The results suggest that LPS tolerance attenuated amygdala inflammation through an anti-inflammatory compensatory response besides preventing anxiety-like behavior caused by the high-fat maternal diet.

Caloric restriction or cafeteria diet from birth to adulthood increases the sensitivity to ephedrine in anxiety and locomotion in Wistar rats.

INTRODUCTION: Obesity and undernutrition, consequences of malnutrition, have been linked to the development of mental illnesses. Both states have been linked to increased sensitivity to some drugs, but there are few data for this association considering drugs with noradrenergic-dopaminergic action. OBJECTIVE: To evaluate the nutritional status of animals treated with either a caloric restriction (CR) or cafeteria (CAF) diet from birth and their behavior after ephedrine application. METHODS: During the lactation period, 12 litters of Wistar rats (dam + 8 pups) were fed one of three diets: control (n = 4), CR (n = 4), and CAF (n = 4). After weaning, the males were placed in individual boxes and received the same diet as their respective dams. Nutritional assessments were performed after weaning and in adulthood. In adulthood, males received either saline or ephedrine (20 mg/kg) and underwent behavioral tests including the elevated plus-maze, open-field, and food intake tests. RESULTS: The CR group exhibited higher serum high-density lipoprotein (HDL) levels and lower food and caloric intake, weight gain, and fat mass than the control group. The CAF group exhibited lower food intake and higher fat caloric intake, fat mass, and serum low-density lipoprotein (LDL), triglyceride, total cholesterol, and hepatic lipid levels than the control group. These results indicated that the CR and CAF groups had developed undernutrition and obesity, respectively. In the elevated plus-maze and open-field tests, the CR and CAF groups showed lower anxiety-like behaviors than the control group after ephedrine application. This result indicates that the animal's nutritional status (undernutrition or obesity) can enhance ephedrine sensitivity. CONCLUSION: The CR group exhibited undernutrition, whereas the CAF group exhibited obesity. Ephedrine altered anxiety and locomotion in animals that received the CR and CAF diets in manner different than that observed in animals receiving the standard diet.

High-Salt Diet in the Pre- and Postweaning Periods Leads to Amygdala Oxidative Stress and Changes in Locomotion and Anxiety-Like Behaviors of Male Wistar Rats.

High-salt (HS) diets have recently been linked to oxidative stress in the brain, a fact that may be a precursor to behavioral changes, such as those involving anxiety-like behavior. However, to the best of our knowledge, no study has evaluated the amygdala redox status after consuming a HS diet in the pre- or postweaning periods. This study aimed to evaluate the amygdala redox status and anxiety-like behaviors in adulthood, after inclusion of HS diet in two periods: preconception, gestation, and lactation (preweaning); and only after weaning (postweaning). Initially, 18 females and 9 male Wistar rats received a standard (n = 9 females and 4 males) or a HS diet (n = 9 females and 5 males) for 120 days. After mating, females continued to receive the aforementioned diets during gestation and lactation. Weaning occurred at 21-day-old Wistar rats and the male offspring were subdivided: control-control (C-C)-offspring of standard diet fed dams who received a standard diet after weaning (n = 9-11), control-HS (C-HS)-offspring of standard diet fed dams who received a HS diet after weaning (n = 9-11), HS-C-offspring of HS diet fed dams who received a standard diet after weaning (n = 9-11), and HS-HS-offspring of HS diet fed dams who received a HS diet after weaning (n = 9-11). At adulthood, the male offspring performed the elevated plus maze and open field tests. At 152-day-old Wistar rats, the offspring were euthanized and the amygdala was removed for redox state analysis. The HS-HS group showed higher locomotion and rearing frequency in the open field test. These results indicate that this group developed hyperactivity. The C-HS group had a higher ratio of entries and time spent in the open arms of the elevated plus maze test in addition to a higher head-dipping frequency. These results suggest less anxiety-like behaviors. In the analysis of the redox state, less activity of antioxidant enzymes and higher levels of the thiobarbituric acid reactive substances (TBARS) in the amygdala were shown in the amygdala of animals that received a high-salt diet regardless of the period (pre- or postweaning). In conclusion, the high-salt diet promoted hyperactivity when administered in the pre- and postweaning periods. In animals that received only in the postweaning period, the addition of salt induced a reduction in anxiety-like behaviors. Also, regardless of the period, salt provided amygdala oxidative stress, which may be linked to the observed behaviors.

Cafeteria diet administered from lactation to adulthood promotes a change in risperidone sensitivity on anxiety, locomotion, memory, and social interaction of Wistar rats.

PURPOSE: To evaluate the nutritional status and behavior of animals fed a cafeteria diet from the onset of lactation after the addition of risperidone. METHODS: During the lactation period, 14 litters of Wistar rats (dam + 8 pups) were fed one of two diets: control (CTRL; n = 7) or cafeteria (CAF; n = 7). After weaning, the males were placed in individual cages, receiving the same diet as offered to their respective dams. Food and caloric intake, body weight, feed and energy efficiency, and adipose tissue weight were evaluated in the male offspring. In adulthood, they were assigned to receive treatment with saline (CTRL-S, CAF-S) or risperidone (CTRL-R, CAF-R) (n = 21 in each group). They then underwent behavioral testing, which included the elevated plus maze, open field, object recognition, and social interaction tests. Variance analysis (ANOVA) was used, followed by Newman-Keuls when p-values were < 0.05. RESULTS: The CAF group exhibited higher caloric intake, weight gain, feed efficiency, and adipose tissue than the CTRL group. The animals in the CAF group exhibited oxidative stress characteristics in the hippocampus, which may have compromised the function of this structure and promoted behavioral changes. The CAF-S group exhibited anxiety, as indicated by the greater number of entrances and time spent in the center of the open field. They also showed greater locomotion through a greater number of quadrants traveled. CAF-S animals also demonstrated memory impairments, assessed using the object recognition test, and decreased social interaction. The CAF-R group demonstrated anxiety and decreased locomotion in the open field. There was a decrease in their interaction with both objects in the object recognition test. The CAF-R group obtained greater sociability in the social interaction test. Such effects may be associated with changes in the serotonergic system of these animals. CONCLUSION: Risperidone administered to animals on a cafeteria diet led to a greater reduction in locomotion, had an anxiogenic effect, caused impaired memory, and improved social interaction.