ABSTRACT
BACKGROUND: To assess oxidative effects induced by a high-calorie diet on the retina of Wistar rats and test the antioxidative effects of carnosine supplementation. METHODS: Wistar rats were randomly divided into the following groups: standard diet (SD), high-calorie diet (HcD), standard diet + carnosine (SD + Car), and high-calorie diet + carnosine (HcD + Car). The body weight, adiposity index, plasma glucose, total lipids, high-density lipoprotein (HDL), low-density lipoprotein (LDL), uric acid, creatinine, and triglycerides of the animals were evaluated. The retinas were analyzed for markers of oxidative stress. Hydrogen peroxide production was assessed by 2',7'-dichlorodihydrofluorescein diacetate (DCF) oxidation. The total glutathione (tGSH), total antioxidant capacity (TAC), protein carbonyl, and sulfhydryl groups of the antioxidant system were analyzed. RESULTS: TAC levels increased in the retinas of the SD + Car group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the HcD group (p < 0.05). The levels of GSH and the GSSH:GSSG ratio were increased in the HcD + Car group compared to the SD + Car group (p < 0.05). An increase in the retinal carbonyl content was observed in the HcD group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the SD + Car group (p < 0.05). A high-calorie diet (HcD) was also associated with a decrease in retinal sulfhydryl-type levels compared to the SD group (p < 0.05). CONCLUSION: The results suggest that feeding a high-calorie diet to rats can promote an increase in carbonyl content and a reduction in sulfhydryl groups in their retinas. The administration of carnosine was not effective in attenuating these oxidative markers. TRIAL REGISTRATION: Animal Ethics Committee of Botucatu Medical School - Certificate number 1292/2019.
Subject(s)
Antioxidants , Carnosine , Rats , Animals , Antioxidants/pharmacology , Carnosine/pharmacology , Rats, Wistar , Oxidative Stress , Diet , Dietary SupplementsABSTRACT
Research background: The extensive cultivation of bananas (Musa sp.) is related to producing tons of residues, such as leaves, pseudostems and bracts (inflorescences). The banana bract is a commercially interesting residue due to its dietary fibre content and high antioxidant potential. With this in mind, this study evaluates the effects of administering banana bract flour in animal models fed a cafeteria diet. Experimental approach: Thirty-two male rats were divided into 4 groups: (i) control diet, (ii) control diet with 10 % banana bract flour, (iii) hypercaloric diet, and (iv) hypercaloric diet with 10 % bract banana flour. The study was conducted for 12 weeks and included analysis of phenolic compounds, assessment of the antioxidant effect of banana bract flour, determination of serum biochemical parameters (glucose, total cholesterol, triglycerides, aspartate aminotransferase (AST), alanine transaminase (ALT), amylase, albumin, uric acid, creatine, total protein, and oral glucose), determination of faecal fat content, and histomorphological analysis of the liver, pancreas and adipose tissue. In addition, molecular parameters such as IL6, total and phosphorylated JNK, total and phosphorylated IKKß, TNFα, TLR4 and HSP70 were determined. Results and conclusions: The banana bract flour showed a high content of phenolic compounds and an antioxidant effect. The in vivo results suggest that the supplementation of a hypercaloric diet with banana bract flour prevented pathological damage by reducing total cholesterol and glucose amounts, which may imply a hepatoprotective effect of this supplement. Thus, using banana bract flour as a supplement can increase the consumption of fibre, antioxidants and bioactive compounds. Novelty and scientific contribution: The development of flour from banana waste and its inclusion in the diet can prevent and/or help treat obesity. In addition, the use of banana bracts can help protect the environment, as they are considered a source of waste by the food industry.
ABSTRACT
The present study was designed to investigate the effects of Gundelia tournefortii L. plant extract on different tissues in terms of DNA damage, biochemical and antioxidant parameter values in rats with high-calorie diets. With this aim, Wistar albino male rats were divided into 4 groups containing 6 rats each and the study was completed over 12 weeks duration. At the end of the implementation process over the 12 weeks, rats were sacrificed and blood and tissue samples were obtained. Analyses were performed on blood and tissue samples. According to results for DNA damage (8-OHdG), in brain tissue the OG2 group was significantly reduced compared to the NC group. For MDA results in liver tissue, OG1 and OG2 groups were determined to increase by a significant degree compared to the control group, while the OG2 group was also increased significantly compared to the obese group. In terms of the other parameters, comparison between the groups linked to consumption of a high calorie diet (HCD) and administration of Gundelia tournefortii L. in terms of antioxidant activities and serum samples obtained statistically significant results. Gundelia tournefortii L. plant extracts had effects that may be counted as positive on antioxidant parameter activity and were especially identified to improve DNA damage and MDA levels in brain tissues. Additionally, consumption of Gundelia tournefortii L. plant extract in the diet may have antiobesity effects; thus, it should be evaluated for use as an effective weight-loss method and as a new therapeutic agent targeting obesity.
O presente estudo foi desenhado para investigar os efeitos do extrato da planta Gundelia tournefortii L. em diferentes tecidos em termos de danos ao DNA, valores de parâmetros bioquímicos e antioxidantes em ratos com dietas hipercalóricas. Com esse objetivo, ratos Wistar albinos machos foram divididos em 4 grupos contendo 6 ratos cada e o estudo foi concluído ao longo de 12 semanas de duração. No final desse processo de implementação, os ratos foram sacrificados e amostras de sangue e tecido foram obtidas. As análises foram realizadas em amostras de sangue e tecido. De acordo com os resultados para danos ao DNA (8-OHdG), no tecido cerebral o grupo OG2 foi significativamente reduzido em comparação com o grupo NC. Para os resultados de MDA no tecido hepático, os grupos OG1 e OG2 aumentaram significativamente em comparação ao grupo controle, enquanto o grupo OG2 também aumentou significativamente em comparação ao grupo obeso. Quanto aos demais parâmetros, a comparação entre os grupos ligados ao consumo de dieta hipercalórica (DC) e à administração de Gundelia tournefortii L. em termos de atividades antioxidantes e amostras de soro obteve resultados estatisticamente significativos. Os extratos de plantas de Gundelia tournefortii L. tiveram efeitos que podem ser considerados positivos na atividade dos parâmetros antioxidantes e foram especialmente identificados para melhorar os danos ao DNA e os níveis de MDA nos tecidos cerebrais. Além disso, o consumo de extrato vegetal de Gundelia tournefortii L. na dieta pode ter efeitos antiobesidade; portanto, deve ser avaliado para uso como um método eficaz de perda de peso e como um novo agente terapêutico voltado para a obesidade.
Subject(s)
Male , Animals , Rats , Antioxidants/analysis , Asteraceae/chemistry , Diet/adverse effects , Rats, Wistar/anatomy & histology , Rats, Wistar/genetics , Rats, Wistar/blood , Mice, ObeseABSTRACT
Abstract The present study was designed to investigate the effects of Gundelia tournefortii L. plant extract on different tissues in terms of DNA damage, biochemical and antioxidant parameter values in rats with high-calorie diets. With this aim, Wistar albino male rats were divided into 4 groups containing 6 rats each and the study was completed over 12 weeks duration. At the end of the implementation process over the 12 weeks, rats were sacrificed and blood and tissue samples were obtained. Analyses were performed on blood and tissue samples. According to results for DNA damage (8-OHdG), in brain tissue the OG2 group was significantly reduced compared to the NC group. For MDA results in liver tissue, OG1 and OG2 groups were determined to increase by a significant degree compared to the control group, while the OG2 group was also increased significantly compared to the obese group. In terms of the other parameters, comparison between the groups linked to consumption of a high calorie diet (HCD) and administration of Gundelia tournefortii L. in terms of antioxidant activities and serum samples obtained statistically significant results. Gundelia tournefortii L. plant extracts had effects that may be counted as positive on antioxidant parameter activity and were especially identified to improve DNA damage and MDA levels in brain tissues. Additionally, consumption of Gundelia tournefortii L. plant extract in the diet may have antiobesity effects; thus, it should be evaluated for use as an effective weight-loss method and as a new therapeutic agent targeting obesity.
Resumo O presente estudo foi desenhado para investigar os efeitos do extrato da planta Gundelia tournefortii L. em diferentes tecidos em termos de danos ao DNA, valores de parâmetros bioquímicos e antioxidantes em ratos com dietas hipercalóricas. Com esse objetivo, ratos Wistar albinos machos foram divididos em 4 grupos contendo 6 ratos cada e o estudo foi concluído ao longo de 12 semanas de duração. No final desse processo de implementação, os ratos foram sacrificados e amostras de sangue e tecido foram obtidas. As análises foram realizadas em amostras de sangue e tecido. De acordo com os resultados para danos ao DNA (8-OHdG), no tecido cerebral o grupo OG2 foi significativamente reduzido em comparação com o grupo NC. Para os resultados de MDA no tecido hepático, os grupos OG1 e OG2 aumentaram significativamente em comparação ao grupo controle, enquanto o grupo OG2 também aumentou significativamente em comparação ao grupo obeso. Quanto aos demais parâmetros, a comparação entre os grupos ligados ao consumo de dieta hipercalórica (DC) e à administração de Gundelia tournefortii L. em termos de atividades antioxidantes e amostras de soro obteve resultados estatisticamente significativos. Os extratos de plantas de Gundelia tournefortii L. tiveram efeitos que podem ser considerados positivos na atividade dos parâmetros antioxidantes e foram especialmente identificados para melhorar os danos ao DNA e os níveis de MDA nos tecidos cerebrais. Além disso, o consumo de extrato vegetal de Gundelia tournefortii L. na dieta pode ter efeitos antiobesidade; portanto, deve ser avaliado para uso como um método eficaz de perda de peso e como um novo agente terapêutico voltado para a obesidade.
ABSTRACT
Abstract The present study was designed to investigate the effects of Gundelia tournefortii L. plant extract on different tissues in terms of DNA damage, biochemical and antioxidant parameter values in rats with high-calorie diets. With this aim, Wistar albino male rats were divided into 4 groups containing 6 rats each and the study was completed over 12 weeks duration. At the end of the implementation process over the 12 weeks, rats were sacrificed and blood and tissue samples were obtained. Analyses were performed on blood and tissue samples. According to results for DNA damage (8-OHdG), in brain tissue the OG2 group was significantly reduced compared to the NC group. For MDA results in liver tissue, OG1 and OG2 groups were determined to increase by a significant degree compared to the control group, while the OG2 group was also increased significantly compared to the obese group. In terms of the other parameters, comparison between the groups linked to consumption of a high calorie diet (HCD) and administration of Gundelia tournefortii L. in terms of antioxidant activities and serum samples obtained statistically significant results. Gundelia tournefortii L. plant extracts had effects that may be counted as positive on antioxidant parameter activity and were especially identified to improve DNA damage and MDA levels in brain tissues. Additionally, consumption of Gundelia tournefortii L. plant extract in the diet may have antiobesity effects; thus, it should be evaluated for use as an effective weight-loss method and as a new therapeutic agent targeting obesity.
Resumo O presente estudo foi desenhado para investigar os efeitos do extrato da planta Gundelia tournefortii L. em diferentes tecidos em termos de danos ao DNA, valores de parâmetros bioquímicos e antioxidantes em ratos com dietas hipercalóricas. Com esse objetivo, ratos Wistar albinos machos foram divididos em 4 grupos contendo 6 ratos cada e o estudo foi concluído ao longo de 12 semanas de duração. No final desse processo de implementação, os ratos foram sacrificados e amostras de sangue e tecido foram obtidas. As análises foram realizadas em amostras de sangue e tecido. De acordo com os resultados para danos ao DNA (8-OHdG), no tecido cerebral o grupo OG2 foi significativamente reduzido em comparação com o grupo NC. Para os resultados de MDA no tecido hepático, os grupos OG1 e OG2 aumentaram significativamente em comparação ao grupo controle, enquanto o grupo OG2 também aumentou significativamente em comparação ao grupo obeso. Quanto aos demais parâmetros, a comparação entre os grupos ligados ao consumo de dieta hipercalórica (DC) e à administração de Gundelia tournefortii L. em termos de atividades antioxidantes e amostras de soro obteve resultados estatisticamente significativos. Os extratos de plantas de Gundelia tournefortii L. tiveram efeitos que podem ser considerados positivos na atividade dos parâmetros antioxidantes e foram especialmente identificados para melhorar os danos ao DNA e os níveis de MDA nos tecidos cerebrais. Além disso, o consumo de extrato vegetal de Gundelia tournefortii L. na dieta pode ter efeitos antiobesidade; portanto, deve ser avaliado para uso como um método eficaz de perda de peso e como um novo agente terapêutico voltado para a obesidade.
Subject(s)
Animals , Rats , Asteraceae , Antioxidants , DNA Damage , Plant Extracts/pharmacology , Rats, Wistar , Obesity/drug therapyABSTRACT
The present study was designed to investigate the effects of Gundelia tournefortii L. plant extract on different tissues in terms of DNA damage, biochemical and antioxidant parameter values in rats with high-calorie diets. With this aim, Wistar albino male rats were divided into 4 groups containing 6 rats each and the study was completed over 12 weeks duration. At the end of the implementation process over the 12 weeks, rats were sacrificed and blood and tissue samples were obtained. Analyses were performed on blood and tissue samples. According to results for DNA damage (8-OHdG), in brain tissue the OG2 group was significantly reduced compared to the NC group. For MDA results in liver tissue, OG1 and OG2 groups were determined to increase by a significant degree compared to the control group, while the OG2 group was also increased significantly compared to the obese group. In terms of the other parameters, comparison between the groups linked to consumption of a high calorie diet (HCD) and administration of Gundelia tournefortii L. in terms of antioxidant activities and serum samples obtained statistically significant results. Gundelia tournefortii L. plant extracts had effects that may be counted as positive on antioxidant parameter activity and were especially identified to improve DNA damage and MDA levels in brain tissues. Additionally, consumption of Gundelia tournefortii L. plant extract in the diet may have antiobesity effects; thus, it should be evaluated for use as an effective weight-loss method and as a new therapeutic agent targeting obesity.(AU)
O presente estudo foi desenhado para investigar os efeitos do extrato da planta Gundelia tournefortii L. em diferentes tecidos em termos de danos ao DNA, valores de parâmetros bioquímicos e antioxidantes em ratos com dietas hipercalóricas. Com esse objetivo, ratos Wistar albinos machos foram divididos em 4 grupos contendo 6 ratos cada e o estudo foi concluído ao longo de 12 semanas de duração. No final desse processo de implementação, os ratos foram sacrificados e amostras de sangue e tecido foram obtidas. As análises foram realizadas em amostras de sangue e tecido. De acordo com os resultados para danos ao DNA (8-OHdG), no tecido cerebral o grupo OG2 foi significativamente reduzido em comparação com o grupo NC. Para os resultados de MDA no tecido hepático, os grupos OG1 e OG2 aumentaram significativamente em comparação ao grupo controle, enquanto o grupo OG2 também aumentou significativamente em comparação ao grupo obeso. Quanto aos demais parâmetros, a comparação entre os grupos ligados ao consumo de dieta hipercalórica (DC) e à administração de Gundelia tournefortii L. em termos de atividades antioxidantes e amostras de soro obteve resultados estatisticamente significativos. Os extratos de plantas de Gundelia tournefortii L. tiveram efeitos que podem ser considerados positivos na atividade dos parâmetros antioxidantes e foram especialmente identificados para melhorar os danos ao DNA e os níveis de MDA nos tecidos cerebrais. Além disso, o consumo de extrato vegetal de Gundelia tournefortii L. na dieta pode ter efeitos antiobesidade; portanto, deve ser avaliado para uso como um método eficaz de perda de peso e como um novo agente terapêutico voltado para a obesidade.(AU)
Subject(s)
Animals , Male , Rats , Asteraceae/chemistry , Rats, Wistar/anatomy & histology , Rats, Wistar/blood , Rats, Wistar/genetics , Antioxidants/analysis , Diet/adverse effects , Mice, ObeseABSTRACT
This study aimed to evaluate changes in beige adipocytes at different times of melatonin administration, in the morning (ZT01) or in the evening (ZT11), at 30 mg/kg daily by gavage for 7 weeks or continuously with drinking water in the term of high-calorie diet-induced obesity (HCD). Melatonin received at ZT11 or with drinking water resulted in an increased area of the browning zone in the subcutaneous white adipose tissue (sWAT), even in rats with HCD (compared with Control or HCD, respectively). The beige adipocyte and lipid droplet area after melatonin use were reduced compared to those with HCD and Control, in all administration modes (group ZT01 showed smaller changes compared to ZT11 or with drinking water groups). The fibrosis level decreased and significantly differed in HCD ZT01, HCD ZT11, and HCD water compared to that in HCD; moreover, the lowest value determined in HCD water, reached the control parameters. Furthermore, the IL-1b and IL-8 level was decreased in the HCD groups under melatonin treatment at ZT11 or with drinking water compared to that in HCD. The obtained results suggest that melatonin promotes sWAT browning in rats with diet-induced obesity and influences morphological signs of normal rats depending on the time of administration. Different functional activity of beige adipocytes was observed after melatonin was used depending on the time of administration, resulting in heat production and lipolysis (the relative mass of visceral fat was likewise diminished). More rapid browning was observed when melatonin treatment was performed at 1 h before lights-off (ZT11) or continuously via drinking water. Melatonin acted on beige adipocytes of obese rats through changing some parameters such as the area of adipocytes and lipid drops, the number of lipid drops, the relative area browning of sWAT, and the level of tissue fibrosis.
Este estudio tuvo como objetivo evaluar los cambios en los adipocitos beige en diferentes momentos de la administración de melatonina, en la mañana (ZT01) o por la noche (ZT11). Se administraron 30 mg/kg diariamente por sonda durante 7 semanas o continuamente con agua potable durante el periodo de obesidad inducida por una dieta alta en calorías (HCD). La melatonina recibida en ZT11 o con agua potable resultó en un aumento de área dorada en tejido adiposo blanco subcutáneo (sWAT), incluso en ratas con HCD (en comparación con Control o HCD, respectivamente). El área de gotas de lípidos y adipocitos de color beige después del uso de melatonina se redujo en comparación con aquellos con HCD y Control, en todos los modos de administración (el grupo ZT01 mostró cambios más pequeños en comparación con ZT11 o con grupos de agua potable). El nivel de fibrosis disminuyó y difirió significativamente en HCD ZT01, HCD ZT11 y agua HCD, en comparación con el HCD; además, el valor más bajo determinado en agua HCD alcanzó los parámetros de control. Además, el nivel de IL-1b e IL-8 disminuyó en los grupos HCD bajo tratamiento con melatonina en ZT11 o con agua potable en comparación con el de HCD. Los resultados obtenidos sugieren que la melatonina promueve el dorado sWAT en ratas con obesidad inducida por la dieta e influye en los signos morfológicos de las ratas normales dependiendo del momento de la administración. Se observó una actividad funcional diferente de los adipocitos de color beige después de usar melatonina dependiendo del tiempo de administración, dando como resultado la producción de calor y lipólisis (la masa relativa de grasa visceral también disminuyó). Se observó un ennegrecimiento más rápido cuando el tratamiento con melatonina se realizó 1 h antes de apagar las luces (ZT11) o de forma continua en grupos de agua potable. La melatonina actuó en los adipocitos beige de ratas obesas al cambiar algunos parámetros, como el área de adipocitos y gotas de lípidos, el número de gotas de lípidos, el área relativa de ennegrecimiento de sWAT y el nivel de fibrosis tisular.
Subject(s)
Animals , Male , Rats , Adipocytes, Beige/drug effects , Melatonin/administration & dosage , Obesity , Time Factors , Fibrosis , Adipose Tissue/drug effects , Adipose Tissue/pathology , Interleukin-8/drug effects , Diet , Interleukin-1beta/drug effectsABSTRACT
Here, we described the effects of obesity induced by high-calorie diet and its treatment with exenatide, an anti-diabetogenic and potential anti-obesogenic drug derived from the venom of the Gila monster Heloderma suspectum, on the affinity, density, subtypes and intracellular signaling pathways linked to activation of muscarinic acetylcholine receptors (mAChRs) in rat hippocampus. Male Wistar rats were divided into three groups: control (CT), obese induced by high-calorie diet (DIO) and DIO treated with exenatide (DIOâ¯+â¯E). [3H]Quinuclidinyl benzilate specific binding analysis showed that the equilibrium dissociation constant (KD) did not differ among CT, DIO and DIOâ¯+â¯E, indicating that affinity is not affected by high-calorie diet or its treatment with exenatide. On the other hand, the density of mAChRs obtained in DIO animals was lower than that obtained from CT rats, and that DIOâ¯+â¯E restored the density of mAChRs. Immunoprecipitation assays reveal a decrease in the expression of M1 and M3 subtypes of DIO animals when compared with CT. Treatment with exenatide (DIOâ¯+â¯E) restored the expression of the two subtypes similar to obtained from CT. On the other hand, the M2, M4 and M5 mAChR subtypes expression did not differ among CT, DIO and DIOâ¯+â¯E. Carbacol caused a concentration-dependent increase in the accumulation of total [3H] inositol phosphate in CT, DIO and DIOâ¯+â¯E. However, the magnitude of the maximal response to carbachol was lower in DIO when compared with those obtained from CT and DIOâ¯+â¯E animals, which did not differ from each other. Our results indicate that obesity induced by high-calorie diet strongly influences the expression and intracellular signaling coupled to M1-M3 mAChR subtypes. The exenatide ameliorated these effects, suggesting an important role on hippocampal muscarinic cholinergic system. This action of obesity induced by high-calorie diet and its treatment with exenatide might be a key step mediating cellular events important for learning and memory.
Subject(s)
Exenatide/therapeutic use , Hippocampus/drug effects , Obesity/drug therapy , Receptors, Muscarinic/drug effects , Animals , Carbachol/pharmacology , Energy Intake , Exenatide/pharmacology , Glucagon-Like Peptide-1 Receptor/physiology , Hippocampus/physiology , Male , Rats , Rats, Wistar , Receptors, Muscarinic/physiologyABSTRACT
Here, we described the effects of obesity induced by high-calorie diet and its treatment with exenatide, an anti-diabetogenic and potential anti-obesogenic drug derived from the venom of the Gila monster Heloderma suspectum, on the affinity, density, subtypes and intracellular signaling pathways linked to activation of muscarinic acetylcholine receptors (mAChRs) in rat hippocampus. Male Wistar rats were divided into three groups: control (CT), obese induced by high-calorie diet (DIO) and DIO treated with exenatide (DIO+E). [3H]Quinuclidinyl benzilate specific binding analysis showed that the equilibrium dissociation constant (KD) did not differ among CT, DIO and DIO+E, indicating that affinity is not affected by high-calorie diet or its treatment with exenatide. On the other hand, the density of mAChRs obtained in DIO animals was lower than that obtained from CT rats, and that DIO+E restored the density of mAChRs. Immunoprecipitation assays reveal a decrease in the expression of M1 and M3 subtypes of DIO animals when compared with CT. Treatment with exenatide (DIO+E) restored the expression of the two subtypes similar to obtained from CT. On the other hand, the M2, M4 and M5 mAChR subtypes expression did not differ among CT, DIO and DIO+E. Carbacol caused a concentration-dependent increase in the accumulation of total [3H] inositol phosphate in CT, DIO and DIO+E. However, the magnitude of the maximal response to carbachol was lower in DIO when compared with those obtained from CT and DIO+E animals, which did not differ from each other. Our results indicate that obesity induced by high-calorie diet strongly influences the expression and intracellular signaling coupled to M1-M3 mAChR subtypes. The exenatide ameliorated these effects, suggesting an important role on hippocampal muscarinic cholinergic system. This action of obesity induced by high-calorie diet and its treatment with exenatide might be a key step mediating cellular events important for learning and memory.Here, we described the effects of obesity induced by high-calorie diet and its treatment with exenatide, an anti-diabetogenic and potential anti-obesogenic drug derived from the venom of the Gila monster Heloderma suspectum, on the affinity, density, subtypes and intracellular signaling pathways linked to activation of muscarinic acetylcholine receptors (mAChRs) in rat hippocampus. Male Wistar rats were divided into three groups: control (CT), obese induced by high-calorie diet (DIO) and DIO treated with exenatide (DIO+E). [3H]Quinuclidinyl benzilate specific binding analysis showed that the equilibrium dissociation constant (KD) did not differ among CT, DIO and DIO+E, indicating that affinity is not affected by high-calorie diet or its treatment with exenatide. On the other hand, the density of mAChRs obtained in DIO animals was lower than that obtained from CT rats, and that DIO+E restored the density of mAChRs. Immunoprecipitation assays reveal a decrease in the expression of M1 and M3 subtypes of DIO animals when compared with CT. Treatment with exenatide (DIO+E) restored the expression of the two subtypes similar to obtained from CT. On the other hand, the M2, M4 and M5 mAChR subtypes expression did not differ among CT, DIO and DIO+E. Carbacol caused a concentration-dependent increase in the accumulation of total [3H] inositol phosphate in CT, DIO and DIO+E. However, the magnitude of the maximal response to carbachol was lower in DIO when compared with those obtained from CT and DIO+E animals, which did not differ from each other. Our results indicate that obesity induced by high-calorie diet strongly influences the expression and intracellular signaling coupled to M1-M3 mAChR subtypes. The exenatide ameliorated these effects, suggesting an important role on hippocampal muscarinic cholinergic system. This action of obesity induced by high-calorie diet and its treatment with exenatide might be a key step mediating cellular events important for learning and memory.
ABSTRACT
During development, the brain goes through fundamental processes, including organization of neural networks and plasticity. Environmental interventions may change initial brain programming, leading to long-lasting effects and altering the susceptibility to psychopathologies, including depression disorder. It is known that depression is a psychiatric disorder with a high prevalence worldwide, including high rates among adolescents. In this study, we evaluated whether social isolation in the prepubertal period and chronic use of high-fat diet (HFD) may induce depressive-like behavior in male adult rats. We also investigated hippocampal plasticity markers and neurotransmitter systems. We found both social isolation and HFD induced a depressive-like behavior in the forced swimming task. Moreover, chronic HFD reduced synaptic markers in hippocampus, demonstrated by reductions in ßIII-tubulin (neuronal marker), PSD-95, SNAP-25, and neurotrophin-3. The HFD group also presented decreased glutamatergic and GABAergic receptors subunits. On the other hand, stress affected hippocampal brain-derived neurotrophic factor (BDNF) signaling pathways, and increased expression of subunit of the NMDA receptor (NR2A). Both factors (stress and diet) decreased GR in the hippocampus without affecting plasma corticosterone at basal levels. Interactions between early stress and HFD access were observed only in the BNDF receptor (tropomyosin receptor kinase B; TrkB) and synaptophysin. In summary, these findings showed that a brief social isolation and chronic HFD, during a sensitive developmental period, cause depressive-like behavior in adulthood. The mechanisms underlying these behavioral effects may involve changes in the levels of synaptic proteins in hippocampus: HFD consumption appears to affect synaptic markers, while social isolation affected BDNF signaling more significantly.
Subject(s)
Behavior, Animal , Depression/etiology , Depression/physiopathology , Hippocampus/physiopathology , Neuronal Plasticity , Stress, Psychological/complications , Animals , Biomarkers/metabolism , Depression/psychology , Diet, High-Fat , Glutamic Acid/metabolism , Hippocampus/pathology , Male , Models, Biological , Rats, Wistar , Receptors, Glucocorticoid/metabolism , Sexual Maturation , Social Isolation/psychology , Sucrose , gamma-Aminobutyric Acid/metabolismABSTRACT
OBJECTIVE: The theory of fetal programming suggests that low birth weight (LBW) predisposes to greater food intake and increases the chance of overweight and obesity, which are in turn associated to conditions such as metabolic syndrome (MS) and acanthosis nigricans. The study objective was to ascertain whether an association exists between MS, LBW, intake of high-calorie diets, and acanthosis nigricans in children and adolescents with overweight or obesity. MATERIAL AND METHODS: A case-control was conducted on 100 children who attended the overweight and obesity outpatient clinic of the OPD Hospital Civil de Guadalajara "Fray Antonio Alcalde". Subjects were stratified in groups with and without MS based on the criteria of the International Diabetes Federation for children aged less than 16 years. Data on LBW, intake of high-calorie diets for 24-hour dietary recalls (average 2 days a week), and acanthosis nigricans (Simone criteria) were obtained by questioning the parents. Frequencies and logistic regression were calculated using SPSS version 22. RESULTS: The results show that 82% of children and adolescents were obese and 18% overweight, and 73% had MS. MS was associated to LBW (OR: 4.83 [95% CI: 1.9-12.47]), high-calorie diets (OR:136.8 [95% CI: 7.7-2434]), and acanthosis nigricans (OR: 1872 [95% CI: 112.9-31028]). CONCLUSIONS: In children and adolescents with overweight and obesity, LBW, high-calorie diets, and acanthosis nigricans are associated to a higher probability of MS.
Subject(s)
Acanthosis Nigricans/epidemiology , Metabolic Syndrome/epidemiology , Overweight/epidemiology , Prenatal Exposure Delayed Effects , Acanthosis Nigricans/etiology , Adolescent , Case-Control Studies , Child , Child, Preschool , Comorbidity , Diet , Diet Records , Disease Susceptibility , Educational Status , Energy Intake , Female , Humans , Infant, Low Birth Weight , Infant, Newborn , Male , Metabolic Syndrome/etiology , Mexico/epidemiology , Obesity/epidemiology , Obesity/etiology , Overweight/etiology , Pregnancy , PrevalenceABSTRACT
Metabolic syndrome (MS) is a serious public health problem, which can promote neuronal alterations in cognitive regions related to learning and memory processes, such as the hippocampus. However, up to now there has been information of a regional segregation of this damage. In this study, we evaluate the MS effect on the neuronal morphology of the hippocampus. Our results demonstrate that 90days of a high-calorie diet alters the metabolic energy markers causing the MS and causes memory impairments, evaluated by the recognition of novel objects test (NORT). In addition, MS animals showed significant differences in dendritic order, total dendritic length and density of dendritic spines in CA1, CA3 and the dentate gyrus (DG) of the hippocampal area, compared with rats fed with a normocaloric diet (vehicle group). Furthermore, the immunoreactivity to synaptophysin (Syp) decreased in the hippocampus of the MS animals compared to the vehicle group. These results indicate that metabolic alterations induced by the MS affect hippocampal plasticity and hippocampal dependent memory processes.