RESUMO
The most recent American Dietary Guidelines (2020-2025) recommend shifting dietary fats from solid saturated fats to unsaturated oils. Dietary oils contain different compositions of unsaturated fatty acids (UFA). Oleic acid (OA) and linoleic acid (LA) are the most common UFA in dietary oils. How individual UFA in oils regulate immune cell function and cancer risk remains unclear. Here we demonstrated that high-fat diets (HFD) rich either in OA or LA induced a similar degree of murine obesity, but the LA-rich HFD specifically promoted mammary tumor growth. LA impaired antitumor T-cell responses by promoting naïve T-cell apoptosis and inhibiting TNFα production. While exogenous OA and LA were taken up by T cells with similar efficacy, only LA induced significant mitochondrial reactive oxygen species production and lipid peroxidation. Importantly, naïve T cells predominantly expressed epidermal fatty acid binding protein (E-FABP), which is central in facilitating LA mitochondrial transport and cardiolipin incorporation. Genetic depletion of E-FABP rescued LA-impaired T-cell responses and suppressed LA-rich HFD-associated mammary tumor growth. Collectively, these data suggest that dietary oils high in LA promote mammary tumors by inducing E-FABP-mediated T-cell dysfunction. SIGNIFICANCE: These findings suggest that modulation of dietary oil composition and inhibition of E-FABP activity may represent novel strategies to enhance T-cell function in the prevention and treatment of obesity-associated cancers.
Assuntos
Gorduras na Dieta/toxicidade , Proteínas de Ligação a Ácido Graxo/metabolismo , Ácidos Linoleicos/toxicidade , Neoplasias Mamárias Experimentais/patologia , Mitocôndrias/patologia , Linfócitos T/imunologia , Animais , Proteínas de Ligação a Ácido Graxo/genética , Feminino , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Obesidade/fisiopatologia , Linfócitos T/efeitos dos fármacos , Magreza/fisiopatologiaRESUMO
BACKGROUND: Dietary frying oil may have endocrine-disrupting effects, as a feminization effect was observed in cohorts of C57BL/6J male mice fetuses from dams consuming oxidized frying oil (OFO) during pregnancy. OBJECTIVE: The aim of present study was to test the hypothesis that OFO is an anti-androgen. METHODS: In experiment 1, male progeny of Sprague Dawley female rats fed fresh oil or an OFO diet (10 g fat/100 g, from fresh or 24-h-fried soybean oil; [control diet (C) and OFO groups, respectively] from midgestation through lactation were studied. Pups were weaned at 3 wk of age and then consumed their mothers' diet until 9 wk of age. In addition, a group of dams and pups that consumed a high-fat diet (HF; 10 g fried and 20 g fresh soybean oil/100 g) was included to counteract body-weight loss associated with OFO ingestion. Indices of male reproductive development and testosterone homeostasis were measured. In experiment 2, male rats were allocated to C and OFO groups (treated as above) and indices of male fertility compared at 9-10 wk of age. RESULTS: In experiment 1, final body weights of the HF group were lower (17%) than the C group but higher (14%) than the OFO group (P < 0.0001 for each). In addition to abnormalities in seminiferous tubules, HF and OFO groups did not differ from one another, but, compared with the C group, had delayed preputial separation (4.9 d) and reductions in serum testosterone concentrations (17-74%), anogenital distance (8-20%), weights of androgen-dependent tissues (8-30%), testicular testosterone and cholesterol concentrations (30-40%), and mRNA levels of genes involved in steroidogenesis and cholesterol homeostasis (30-70%). In experiment 2, OFO-exposed males had 20% lower sperm motility (P < 0.05); however, when mated to normal females, pregnancy rates and litter sizes did not differ between OFO and C groups. CONCLUSIONS: The anti-androgenic effect of OFO in Sprague Dawley rats was attributed to decreased testicular concentrations of cholesterol (testosterone precursor) and not body-weight loss.
Assuntos
Colesterol/metabolismo , Homeostase/efeitos dos fármacos , Óleo de Soja/toxicidade , Testículo/efeitos dos fármacos , Testosterona/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Culinária , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/toxicidade , Feminino , Masculino , Oxirredução , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Fenômenos Fisiológicos da Nutrição Pré-Natal , Ratos , Ratos Sprague-Dawley , Testículo/metabolismoRESUMO
Background: Palmitic acid (PA) is the main saturated fatty acid naturally occurring in animal fats and vegetable oils. In recent decades, palm oil, an alternative lipid source containing high amounts of PA, has been widely used to replace fish oil in aquafeed. Objective: We investigated the hepatotoxicity of PA in zebrafish and the underlying mechanism. Methods: One-month-old zebrafish fed a high-fat diet (HFD) containing 16% soybean oil and 3 PA-incorporated HFDs [4%, 8%, and 12% PA (12PA)] for 2 wk (experiment 1) and 4 wk (experiment 2) were used to evaluate PA-induced liver damage and endoplasmic reticulum (ER) stress. Germ-free (GF) zebrafish fed low-fat, high-fat, or 12PA diets for 5 d were used to study the direct effects of PA on liver damage (experiment 3). GF zebrafish colonized with HFD or 12PA microbiota for 48 h were used to elucidate the indirect effects of PA-altered microbiota on liver damage (experiment 4). Last, GF zebrafish colonized with HFD or 12PA microbiota were used to evaluate the effects of different microbiotas on PA absorption (experiment 5). Results: In experiment 1, the proportion of PA in the liver linearly increased as its percentage in dietary lipid increased (r2 = 0.83, P < 0.05). In experiment 2, the expression of glucose-regulated protein 78 (Grp78) and C/EBP-homologous protein (Chop) was higher in the 12PA group than in the HFD group (2.2- and 2.7-fold, respectively; P < 0.05). The activity of caspase-12 was increased by 61.1% in the 12PA group compared with the HFD group (P < 0.05). In experiment 3, caspase-12 activity was higher in the 12PA group than in the HFD group (P < 0.05). In experiment 4, GF zebrafish colonized with PA-altered microbiota had higher caspase-12 activity (P < 0.05) than those colonized by HFD microbiota. In experiment 5, PA-altered microbiota promoted PA absorption (P < 0.05) and aggravated ER stress and liver damage in the context of high-PA feeding. Conclusions: The PA-altered microbiota indirectly induced ER stress and liver damage in zebrafish. Moreover, the PA microbiota promoted the absorption of PA, leading to enhanced PA overflow into the liver and aggravated hepatotoxicity of PA in zebrafish.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/microbiologia , Gorduras na Dieta/toxicidade , Estresse do Retículo Endoplasmático , Microbioma Gastrointestinal , Fígado/efeitos dos fármacos , Ácido Palmítico/toxicidade , Ração Animal , Animais , Caspase 12/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Fígado/metabolismo , Óleo de Palmeira/química , Óleo de Palmeira/toxicidade , Peixe-ZebraRESUMO
In recent years, interesterified fat (IF) has been used to replace hydrogenated vegetable fat (HVF), rich in trans isomers, being found in processed foods. Studies involving IF have shown deleterious influences on the metabolic system, similarly to HVF, whereas no studies regarding its influence on the central nervous system (CNS) were performed. Rats from first generation born and maintained under supplementation (3g/Kg, p.o.) of soybean-oil or IF until adulthood were assessed on memory, biochemical and molecular markers in the hippocampus. IF group showed higher saturated fatty acids and linoleic acid and lower docosahexaenoic acid incorporation in the hippocampus. In addition, IF supplementation impaired short and long-term memory, which were related to increased reactive species generation and protein carbonyl levels, decreased catalase activity, BDNF and TrkB levels in the hippocampus. To the best of our knowledge, this is the first study to show that lifelong IF consumption may be related to brain oxidative damage, memory impairments and neurotrophins modifications, which collectively may be present indifferent neurological disorders. In fact, the use of IF in foods was intended to avoid damage from HVF consumption; however this substitute should be urgently reviewed, since this fat can be as harmful as trans fat.
Assuntos
Gorduras na Dieta/toxicidade , Hipocampo/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Triglicerídeos/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Catalase/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Feminino , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Ácido Linoleico/metabolismo , Transtornos da Memória/metabolismo , Transtornos da Memória/psicologia , Memória de Longo Prazo/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Precursores de Proteínas/metabolismo , Proteínas Tirosina Quinases/metabolismo , Ratos Wistar , Receptor trkB , Reconhecimento Psicológico/efeitos dos fármacos , Medição de RiscoRESUMO
A novel medium- and long-chain triacylglycerols (MLCT), with 30% (w/w) medium-chain fatty acids (MCFA) was evaluated for its safety as a dietary fat in mice and rats. The subacute oral toxicity study showed that the maximum tolerated dose exceeded 54.33 g/kg body weight (kg bw)/day. In the 90-day feeding study, no dose-related adverse effects were observed in rats administered diets formulated with different levels of MLCT (2.0, 4.0, and 8.0 g/kg bw/day) as compared to the rapeseed oil control diet. Further safety assessment in pregnant rats did not reveal any significant difference relative to the control at a treatment level up to 8.0 g MLCT/kg bw/day. The results from this study indicated the safe use of MLCT with high contents of MCFA in food products for improving human health.
Assuntos
Gorduras na Dieta/toxicidade , Ácidos Graxos/toxicidade , Triglicerídeos/toxicidade , Animais , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/química , Camundongos , Óleo de Brassica napus/toxicidade , Ratos , Triglicerídeos/químicaRESUMO
BACKGROUND: Pork is an essential component of the diet that has been linked with major degenerative diseases and development of non-alcoholic steatohepatitis (NASH). Previous studies have. Previous studies have demonstrated the in vitro antioxidant activity of silicon (Si). Furthermore, when Si is added to restructured pork (RP) strongly counterbalances the negative effect of high-cholesterol-ingestion, acting as an active hypocholesterolemic and hypolipemic dietary ingredient in aged rats. OBJECTIVE: This study was designed to evaluate the effects of Si vs hydroxytyrosol (HxT) RP on liver antioxidant defense in aged rats fed cholesterol-enriched high saturated/high cholesterol diets as a NASH model. METHODS: Four diets were prepared: Control RP diet (C) with non-added cholesterol; Cholesterol-enriched high-saturated/high-cholesterol control RP diet (CHOL-C) with added cholesterol and cholic acid; Si- or HxT-RP cholesterol-enriched high-saturated/high-cholesterol diets (CHOL-Si and CHOL-HxT). Groups of six male Wistar rats (1-yr old) were fed these modified diets for eight weeks. Total cholesterol, hepatosomatic index, liver Nrf2 and antioxidant (CAT, SOD, GSH, GSSG, GR, GPx) markers were determined. RESULTS: Both CHOL-Si and CHOL-HxT diets enhanced the liver antioxidant status, reduced hepatosomatic index and increased SOD actvity. Hydrogen peroxide removal seemed to be involved, explaining that the value of redox index was even lower than C without changing the CAT activity. CHOL-Si results were quite better than CHOL-HxT in most measured parameters. CONCLUSIONS: Our study suggests that Si incorporated into RP matrix was able to counterbalance, more efficiently than HxT, the deleterious effect of consuming a high-saturated/high-cholesterol diet, by improving the liver antioxidant defenses in the context of NASH.
Assuntos
Antioxidantes/uso terapêutico , Gorduras na Dieta/toxicidade , Fígado/metabolismo , Carne , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Álcool Feniletílico/análogos & derivados , Dióxido de Silício/uso terapêutico , Envelhecimento , Ração Animal/efeitos adversos , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Peso Corporal/efeitos dos fármacos , Catalase/sangue , Colesterol na Dieta/administração & dosagem , Colesterol na Dieta/toxicidade , Ácido Cólico/administração & dosagem , Ácido Cólico/toxicidade , Coloides , Gorduras na Dieta/administração & dosagem , Avaliação Pré-Clínica de Medicamentos , Ácidos Graxos/administração & dosagem , Ácidos Graxos/toxicidade , Glutationa/sangue , Hipolipemiantes/administração & dosagem , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Masculino , Carne/efeitos adversos , Fator 2 Relacionado a NF-E2/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Oxirredução , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Ratos , Ratos Wistar , Dióxido de Silício/administração & dosagem , Dióxido de Silício/farmacologia , Superóxido Dismutase/sangue , Sus scrofa , SuínosRESUMO
Matcha is a kind of powdered green tea produced by grinding with a stone mill. In the present study, the preventive effects of the aqueous extract (water-soluble) and residue (water-insoluble) of Matcha on the antioxidant status and lipid and glucose levels in mice fed a high-fat diet were investigated. Mice were fed seven different experimental diets for 4 weeks: a normal diet control (NC), a high-fat diet (HF), a high-fat diet with 0.025% Matcha (MLD), a high-fat diet with 0.05% Matcha (MMD), a high-fat diet with 0.075% Matcha (MHD), a high-fat diet with 0.05% Matcha aqueous extracts (ME), and a high-fat diet with 0.05% Matcha residues (MR). It was found that serum total cholesterol (TC) and triglyceride (TG) levels of the MHD group were significantly decreased compared to those of the HF group. Furthermore, in the MHD group, the level of high-density lipoprotein-cholesterol (HDL-C) was elevated, on the contrary the level of low-density lipoprotein-cholesterol (LDL-C) was suppressed. Moreover, Matcha could significantly lower the blood glucose levels, and improve the superoxide dismutase (SOD) activity and malondialdehyde (MAD) contents both in serum and liver; besides, the serum GSH-Px activity indicated that the oxidative stress caused by HF could be reversed by administration of Matcha. These findings suggest that Matcha has beneficial effects through the suppression of the blood glucose (BG) accumulation and promotion of the lipid metabolism and antioxidant activities. Moreover, the water-insoluble part of Matcha is suggested to play an important role in the suppression of diet-induced high levels of lipid and glucose.
Assuntos
Antioxidantes/metabolismo , Glicemia/efeitos dos fármacos , Gorduras na Dieta/toxicidade , Lipídeos/sangue , Extratos Vegetais/farmacologia , Chá/química , Animais , Peso Corporal/efeitos dos fármacos , Gorduras na Dieta/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/químicaRESUMO
In recent decades, the increased consumption of processed foods, which are rich in hydrogenated vegetable fat (HVF), has led to a decreased consumption of fish and oilseed, rich in omega-3 fatty acids. This eating habit provides an increased intake of trans fatty acids (TFA), which may be related to neuropsychiatric conditions, including inattention and hyperactivity. In this study, we evaluated the potential connection between prolonged trans fat consumption and development of hyperactivity-like symptoms in rats using different behavioral paradigms. Trans fat intake for 10 months (Experiment 1), as well as during pregnancy and lactation across two sequential generations of rats, (Experiment 4) induced active coping in the forced swimming task (FST). In addition, HVF supplementation was associated with increased locomotion before and after amphetamine (AMPH) administration (Experiment 2). Similarly, HVF supplementation during pregnancy and lactation were associated with increased locomotion in both young and adult rats (Experiment 3). Furthermore, trans fat intake across two sequential generations increased locomotor and exploratory activities following stressors (Experiment 4). From these results, we suggest that chronic consumption of trans fat is able to enhance impulsiveness and reactivity to novelty, facilitating hyperactive behaviors.
Assuntos
Gorduras na Dieta/toxicidade , Agitação Psicomotora/fisiopatologia , Ácidos Graxos trans/toxicidade , Adaptação Psicológica/fisiologia , Acatisia Induzida por Medicamentos/fisiopatologia , Anfetamina/farmacologia , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Comportamento Exploratório/fisiologia , Feminino , Comportamento Impulsivo/fisiologia , Lactação , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Óleos de Plantas/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Agitação Psicomotora/etiologia , Distribuição Aleatória , Ratos Wistar , Estresse Psicológico/fisiopatologiaRESUMO
The aim of the work was to define the influence of dietary supplementation with GM (genetically modified) GT#4 flaxseed cake enriched in polyphenols on inflammation development in mice liver. Mice were given ad libitum isoprotein diets: (1) standard diet; (2) high-fat diet rich in lard, high-fat diet enriched with 30% of (3) isogenic flax Linola seed cake; and (4) GM GT#4 flaxseed cake; for 96 days. Administration of transgenic and isogenic seed cake lowered body weight gain, of transgenic to the standard diet level. Serum total antioxidant status was statistically significantly improved in GT#4 flaxseed cake group and did not differ from Linola. Serum thiobarbituric acid reactive substances, lipid profile and the liver concentration of pro-inflammatory cytokine tumor necrosis factor-α were ameliorated by GM and isogenic flaxseed cake consumption. The level of pro-inflammatory cytokine interferon-γ did not differ between mice obtaining GM GT#4 and non-GM flaxseed cakes. The C-reactive protein concentration was reduced in animals fed GT#4 flaxseed cake and did not differ from those fed non-GM flaxseed cake-based diet. Similarly, the liver structure of mice consuming diets enriched in flaxseed cake was improved. Dietetic enrichment with GM GT#4 and non-GM flaxseed cakes may be a promising solution for health problems resulting from improper diet.
Assuntos
Linho/enzimologia , Glucosiltransferases/genética , Hipercolesterolemia/dietoterapia , Inflamação/dietoterapia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/enzimologia , Solanum/enzimologia , Ração Animal , Animais , Antioxidantes/análise , Proteína C-Reativa/análise , Gorduras na Dieta/toxicidade , Feminino , Linho/genética , Hipercolesterolemia/sangue , Hipercolesterolemia/induzido quimicamente , Hipercolesterolemia/prevenção & controle , Inflamação/sangue , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Interferon gama/sangue , Peroxidação de Lipídeos , Lipídeos/sangue , Fígado/química , Fígado/ultraestrutura , Masculino , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos , Estresse Oxidativo , Plantas Geneticamente Modificadas/genética , Proteínas Recombinantes de Fusão/genética , Solanum/genética , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Fator de Necrose Tumoral alfa/análise , Aumento de PesoRESUMO
Recent evidence has demonstrated that consumption of high fat diets can trigger brain inflammation and subsequent injury in the absence of any peripheral inflammatory signaling. Here we sought to investigate whether a link exists between the concentration of highly saturated fats in the diet and the development of inflammation in the brain of rats and, whether the source of the saturated fat was an important factor in this process. Adult male rats had access to diets with a moderate level of total fat (32% of calories as fat) varying in level of saturated fat [low (20%) vs high (>60%)] and its source (butter or coconut oil). After 8 weeks of diet exposure peripheral and central tissues were collected for analysis of inflammatory signals. Neither blood nor white adipose tissue exhibited any changes in inflammatory mediators regardless of the saturated fat content or the source. In the brain however, we observed significant hypothalamic upregulation of the expression of markers of glial activation as well as of interleukin (IL)-1,6 and nuclear factor (NF)-IL-6, which were highest in the group fed the butter-based diets. The increase in these inflammatory mediators had no effect on basal body temperature or the temperature response to systemic lipopolysaccharide (LPS). The present results indicate that hypothalamic inflammation associated with consumption of diets high in fat is directly linked to the saturated fat content as well as the source of that fat. These effects are likely linked to other pathophysiological changes in the regulation of metabolism.
Assuntos
Gorduras na Dieta/toxicidade , Hipotálamo/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Temperatura Corporal , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo , Interleucina-6/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
Dysfunction of the blood-brain barrier (BBB) is an early pathological feature of vascular dementia and Alzheimer's disease (AD) and is triggered by inflammatory stimuli. Probucol is a lipid-lowering agent with potent anti-oxidant properties once commonly used for the treatment of cardiovascular disease. Probucol therapy was found to stabilize cognitive symptoms in elderly AD patients, whereas in amyloid transgenic mice probucol was shown to attenuate amyloidosis. However, the mechanisms underlying the effects of probucol have note been determined. In the present study we investigated whether probucol can prevent BBB disturbances induced by chronic ingestion of proinflammatory diets enriched with either 20% (w/w) saturated fats (SFA) or 1% (w/w) cholesterol. Mice were fed the diets for 12 weeks before they were killed and BBB integrity was measured. Mice maintained on either the SFA- or cholesterol-supplemented diets were found to have a 30- and sevenfold greater likelihood of BBB dysfunction, respectively, as determined by the parenchymal extravasation of plasma-derived immunoglobulins and endogenous lipoprotein enrichment with ß-amyloid. In contrast, mice fed the SFA- or cholesterol-enriched diets that also contained 1% (w/w) probucol showed no evidence of BBB disturbance. The parenchymal expression of glial fibrillary acidic protein, a marker of cerebrovascular inflammation, was significantly greater in mice fed the SFA-enriched diet. Plasma lipid, ß-amyloid and apolipoprotein B levels were not increased by feeding of the SFA- or cholesterol-enriched diets. However, mice fed the SFA- or cholesterol-enriched diets did exhibit increased plasma non-esterified fatty acid levels that were not reduced by probucol. The data suggest that probucol prevents disturbances of BBB induced by chronic ingestion of diets enriched in SFA or cholesterol by suppressing inflammatory pathways rather than by modulating plasma lipid homeostasis.
Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Transtornos Cerebrovasculares/prevenção & controle , Colesterol na Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/administração & dosagem , Hipolipemiantes/farmacologia , Probucol/farmacologia , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/metabolismo , Animais , Apolipoproteínas B/sangue , Apolipoproteínas B/metabolismo , Barreira Hematoencefálica/metabolismo , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/metabolismo , Colesterol na Dieta/toxicidade , Dieta/efeitos adversos , Gorduras na Dieta/toxicidade , Ácidos Graxos/efeitos adversos , Feminino , Proteína Glial Fibrilar Ácida , Imunoglobulinas/metabolismo , Inflamação/metabolismo , Inflamação/prevenção & controle , Lipoproteínas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Distribuição AleatóriaRESUMO
Obesity is related to an elevated risk of dementia and the physiologic mechanisms whereby fat adversely affects the brain are poorly understood. The present investigation analyzed the effect of a high fat diet (HFD) on brain steatosis and oxidative stress and the intracellular mediators involved in signal transduction, as well as the protection offered by grape seed and skin extract (GSSE). HFD induced ectopic deposition of cholesterol and phospholipid but not triglyceride. Moreover brain lipotoxicity is linked to an oxidative stress characterized by increased lipoperoxidation and carbonylation, inhibition of glutathione peroxidase and superoxide dismutase activities, depletion of manganese and a concomitant increase in ionizable calcium and acetylcholinesterase activity. Importantly GSSE alleviated all the deleterious effects of HFD treatment. Altogether our data indicated that HFD could find some potential application in the treatment of manganism and that GSSE should be used as a safe anti-lipotoxic agent in the prevention and treatment of fat-induced brain injury.
Assuntos
Antioxidantes/farmacologia , Encefalopatias/induzido quimicamente , Gorduras na Dieta/antagonistas & inibidores , Gorduras na Dieta/toxicidade , Extrato de Sementes de Uva/farmacologia , Vitis/química , Acetilcolinesterase/metabolismo , Animais , Encéfalo/enzimologia , Encefalopatias/metabolismo , Encefalopatias/patologia , Cálcio/metabolismo , Cromatografia Líquida de Alta Pressão , Dieta , Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Manganês/metabolismo , Espectrometria de Massas , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Sementes/química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
SCOPE: To characterize the effects of ingesting the common foodborne mycotoxin deoxynivalenol (DON) on body weight and composition in the high-fat (HF) diet-induced obese mice, a model of human obesity. METHODS AND RESULTS: Female B6C3F1 mice were initially fed HF diets containing 45% kcal (HF45) or 60% kcal (HF60) as fat for 94 days to induce obesity. Half of each group was either continued on unamended HF diets or fed HF diets containing 10 mg/kg DON (DON-HF45 or DON-HF60) for another 54 days. Additional control mice were fed a low-fat (LF) diet containing 10% kcal as fat for the entire 148-day period. DON induced rapid decreases in body weights and fat mass, which stabilized to those of the LF control within 11 days. These effects corresponded closely to a robust transient decrease in food consumption. While lean body mass did not decline in DON-fed groups, further increases were suppressed. DON exposure reduced plasma insulin, leptin, insulin-like growth factor 1, and insulin-like growth factor acid labile subunit as well as increased hypothalamic mRNA level of the orexigenic agouti-related protein. CONCLUSION: DON-mediated effects on body weight, fat mass, food intake, and hormonal levels in obese mice were consistent with a state of chronic energy restriction.
Assuntos
Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Obesidade/metabolismo , Tricotecenos/farmacologia , Tecido Adiposo/efeitos dos fármacos , Proteína Relacionada com Agouti/efeitos dos fármacos , Proteína Relacionada com Agouti/genética , Animais , Proteínas de Transporte/sangue , Proteínas de Transporte/efeitos dos fármacos , Gorduras na Dieta/toxicidade , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Feminino , Glicoproteínas/sangue , Glicoproteínas/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiologia , Insulina/sangue , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Leptina/sangue , Camundongos , Camundongos Obesos , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , RNA MensageiroRESUMO
High dietary fat causes increased bile acid secretion into the gastrointestinal tract and is associated with colon cancer. Since the bile acid deoxycholic acid (DOC) is suggested to be important in colon cancer etiology, this study investigated whether DOC, at a high physiologic level, could be a colon carcinogen. Addition of 0.2% DOC for 8-10 months to the diet of 18 wild-type mice induced colonic tumors in 17 mice, including 10 with cancers. Addition of the antioxidant chlorogenic acid at 0.007% to the DOC-supplemented diet significantly reduced tumor formation. These results indicate that a high fat diet in humans, associated with increased risk of colon cancer, may have its carcinogenic potential mediated through the action of bile acids, and that some dietary anti-oxidants may ameliorate this carcinogenicity.
Assuntos
Ácido Clorogênico/farmacologia , Neoplasias do Colo/etiologia , Ácido Desoxicólico/toxicidade , Gorduras na Dieta/toxicidade , Animais , Antioxidantes/farmacologia , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/toxicidade , Testes de Carcinogenicidade , Ácido Desoxicólico/metabolismo , Masculino , Camundongos , RiscoRESUMO
This study evaluates the protective role of Clerodendron glandulosum.Coleb (CG) aqueous extract against high fat diet/fatty acid induced lipotoxicity in experimental models of non-alcoholic steatohepatitis (NASH). Supplementation of NASH mice with CG extract (1% and 3% in high fat diet for 16 weeks) prevented high fat diet induced elevation in liver enzymes, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status and histopathological damage to hepatocytes. Furthermore, results from in vitro study indicates, addition of CG extract (20-200 µg/ml for 24h) to HepG2 cells minimizes oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that CG extract has the potential of preventing high fat/fatty acid induced NASH.
Assuntos
Clerodendrum/química , Gorduras na Dieta/antagonistas & inibidores , Gorduras na Dieta/toxicidade , Ácidos Graxos/antagonistas & inibidores , Ácidos Graxos/toxicidade , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/tratamento farmacológico , Alanina Transaminase/sangue , Animais , Antioxidantes/análise , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dieta , Fígado Gorduroso/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Some physico-chemical properties of fat released from chicken during grilling process were evaluated and the results showed that refractive index and saponification values were not affected by grilling process. However, serious increases in oxidative deterioration parameters and color were noticed. The main objective of this study was to characterize the effect of grilled fat on body weight, liver function, chromosomal aberrations and micronucleus formation in rats. Eight-week-old Swiss male albino rats, weighing approximately 90 g were used in this study. Rats were fed on a diet containing grilled fat for two months showed insignificant decrease in body weight compared to the control except, the eighth week (last weighing). The serum analysis should that aspartate transaminase (AST), cholesterol, creatinine and urea levels increased significantly whereas, alanine transaminase (ALT), and triglyceride levels were not affected. Also, cytogenetic analysis showed various types of chromosomal aberrations, i.e., chromatide breaks, ring chromosome, fragment chromosome, and end to end association chromosomes and insignificant increase in the frequency of micronucleated cells.
Assuntos
Galinhas , Gorduras na Dieta/farmacologia , Gorduras na Dieta/toxicidade , Carne/análise , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Peso Corporal/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Aberrações Cromossômicas , Cor , Culinária , Óleo de Milho/toxicidade , Dano ao DNA , Testes de Função Hepática , Masculino , Testes para Micronúcleos , RatosRESUMO
Wheat grass is used as a general health tonic and is reported to be effective against several medical disorders, although detailed literature is not available. Besides drug therapy, a number of medicinal plants are effective in treating hyperlipidemia. This study examined the effects of wheat grass on high-fat diet-induced hyperlipidemia in rabbits. Thirty rabbits were divided into 3 groups of 10 rabbits each, group I receiving a control diet, group II a high-fat diet and group III a high-fat diet together with wheat grass over a period of 10 weeks. Fasting serum samples from the animals were analyzed for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), reduced glutathione (GSH) and vitamin C, and the results were compared. The high-fat diet resulted in hyperlipidemia and an increase in oxidative stress, indicated by a significant rise in MDA levels, whereas antioxidant levels of GSH and vitamin C were significantly reduced. Wheat grass supplementation with a high-fat diet resulted in improved lipid levels (decreased total cholesterol and increased HDL-C) together with significantly reduced MDA levels and increased GSH and vitamin C levels. These results indicate the beneficial role of wheat grass in ameliorating hyperlipidemia and the associated oxidative stress.
Assuntos
Antioxidantes/farmacologia , Hiperlipidemias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Triticum/química , Animais , Ácido Ascórbico/metabolismo , Gorduras na Dieta/toxicidade , Feminino , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Hiperlipidemias/fisiopatologia , Masculino , Malondialdeído/metabolismo , Fitoterapia/métodos , Preparações de Plantas/farmacologia , CoelhosRESUMO
RATIONALE: Although dietary fatty acids are a major fuel for the heart, little is known about the direct effects of dietary fatty acids on gene regulation in the intact heart. OBJECTIVE: To study the effect of dietary fatty acids on cardiac gene expression and explore the functional consequences. METHODS AND RESULTS: Oral administration of synthetic triglycerides composed of one single fatty acid altered cardiac expression of numerous genes, many of which are involved in the oxidative stress response. The gene most significantly and consistently upregulated by dietary fatty acids encoded Angiopoietin-like protein (Angptl)4, a circulating inhibitor of lipoprotein lipase expressed by cardiomyocytes. Induction of Angptl4 by the fatty acid linolenic acid was specifically abolished in peroxisome proliferator-activated receptor (PPAR)beta/delta(-/-) and not PPARalpha(-/-) mice and was blunted on siRNA-mediated PPARbeta/delta knockdown in cultured cardiomyocytes. Consistent with these data, linolenic acid stimulated binding of PPARbeta/delta but not PPARalpha to the Angptl4 gene. Upregulation of Angptl4 resulted in decreased cardiac uptake of plasma triglyceride-derived fatty acids and decreased fatty acid-induced oxidative stress and lipid peroxidation. In contrast, Angptl4 deletion led to enhanced oxidative stress in the heart, both after an acute oral fat load and after prolonged high fat feeding. CONCLUSIONS: Stimulation of cardiac Angptl4 gene expression by dietary fatty acids and via PPARbeta/delta is part of a feedback mechanism aimed at protecting the heart against lipid overload and consequently fatty acid-induced oxidative stress.
Assuntos
Angiopoietinas/metabolismo , Cardiomiopatias/prevenção & controle , Gorduras na Dieta/metabolismo , Ácidos Graxos Insaturados/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo , PPAR delta/metabolismo , PPAR beta/metabolismo , Proteína 4 Semelhante a Angiopoietina , Angiopoietinas/deficiência , Angiopoietinas/genética , Animais , Animais Recém-Nascidos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Células Cultivadas , Citoproteção , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/sangue , Gorduras na Dieta/toxicidade , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos Insaturados/sangue , Ácidos Graxos Insaturados/toxicidade , Retroalimentação Fisiológica , Ácido Linoleico/metabolismo , Peroxidação de Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ácido Oleico/metabolismo , Estresse Oxidativo/genética , PPAR delta/deficiência , PPAR delta/genética , PPAR beta/deficiência , PPAR beta/genética , Interferência de RNA , Fatores de Tempo , Regulação para Cima , Ácido alfa-Linolênico/metabolismoRESUMO
Acrylamide (ACR) and high contents of fat could be found co-existent in many foods processed by high temperature, such as deep-frying and roasting. This study investigated the effect of enhanced fat consumption on deficits of spermatogenesis induced by ACR, and explored potential mechanisms of oxidative damage involved in this pathology in mice. Results show that enhanced feeding of corn oil and pork fat on mice potentiated the decreases of spermatogonia along with mature sperms after treatment of ACR, and that spermatozoa quality is significantly reduced as a result of enhanced feeding of corn oil and pork fat on mice treated with ACR. Moreover, enhanced consumption of corn oil and pork fat potentiated the up-regulation of malondialdehyde (MDA) level in epididymal sperm and cauda epididymides, also up-regulated level of Protein carbonyls (PCOs) in cauda epididymides, of mice after treatment of ACR. Last, enhanced consumption of corn oil and pork fat potentiated the reduced activity of superoxide dismutases (SOD) in epididymal sperm, corpus, and cauda epididymides, also reduced activity of glutathione peroxidase (GPx) in cauda epididymides, of mice treated with ACR. These data suggest that enhanced feeding of corn oil and pork fat on mice potentiates ACR-induced oxidative stress in the epididymis and epididymal sperm and a subsequent effect on spermatogenesis.
Assuntos
Acrilamida/toxicidade , Gorduras na Dieta/toxicidade , Epididimo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Óleo de Milho/toxicidade , Gorduras na Dieta/administração & dosagem , Epididimo/metabolismo , Epididimo/patologia , Glutationa Peroxidase/metabolismo , Cinética , Masculino , Malondialdeído/metabolismo , Produtos da Carne/toxicidade , Camundongos , Carbonilação Proteica/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Superóxido Dismutase/metabolismo , SuínosRESUMO
The male Wistar rats were kept at high fat diet for 90 days and subjected to partial abdominal aortic constriction (PAAC) at 62nd and continued up to 90th day. Similarly, rats were kept at high fat diet for 90 days and subjected to chronic swimming training (CST) at 46th day and continued up to 90th day. Obesity was assessed by % age change in body weight, WHR ratio and adiposity index whereas cardiac hypertrophy was assessed by using index of cardiac hypertrophy, i.e., left ventricular weight, left ventricular weight to body weight, (LVW/BW), left ventricular wall thickness (LVWT), cardiomyocyte diameter, LV, protein content and collagen content. Further, mean arterial blood pressure (MABP) was also recorded. Oxidative stress was assessed by measuring the levels of thiobarbituric acid reactive species (TBARS), levels of superoxide anion generation and levels of reduced glutathione in left ventricular tissue. The PAAC and CST increased the index of cardiac hypertrophy. Moreover, PAAC has significantly increased MABP. Fluvastatin, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, significantly attenuated PAAC induced left ventricular cardiac hypertrophy and MABP whereas no significant change was observed in CST-induced cardiac hypertrophy. Furthermore, fluvastatin significantly attenuated the oxidative stress by decreasing the levels of TBARS and superoxide anion generation and increasing the levels of reduced glutathione. These results suggest that fluvastatin prevented the PAAC-induced cardiac hypertrophy.