Protective effects of beta-glucan extracted from barley against benzo[a]pyrene-induced DNA damage in hepatic cell HepG2

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The effect of gastric dilatation in rats submitted to gasified water ingestion under the hepatic metabolic function

INTRODUÇÃO: O excesso de peso na população aumentou de forma significante nas últimas décadas e as bebidas gasosas tornaram-se um fator ambiental importante no comportamento alimentar das pessoas, sendo os EUA, México e Brasil, nesta ordem, os três maiores paises produtores e consumidores de refrigerantes. OBJETIVO: Investigar os efeitos da dilatação gástrica em ratos submetidos a ingestão de água gaseificada, veículo uniforme para todos os refrigerantes, sobre parâmetros metabólicos da função hepática. MÉTODOS: Foram constituídos dois grupos de 15 ratos acompanhados por 15 semanas. Ao Grupo-I, foram oferecidos 200 g/dia de ração ad libitum e 100 ml de água não gaseificada em 3 períodos diários, ao Grupo-II, foram oferecidos 200 g/dia de ração ad libitum e 100 ml de água gaseificada em 3 períodos diários; em cada grupo,foram calculados a média (x) e o desvio padrão (s); para todos os atributos estudados foi utilizado o método estatístico de teste t pareado, comparando-se GI com GII, testando-se o efeito dos tipos de água. RESULTADOS: Os resultados identificaram que os animais que foram submetidos ao tratamento com água gaseificada (Grupo-II), apresentaram um aumento de transaminase glutâmica pirúvica (TGP) e fosfatase alcalina p<0,01), tendência de aumento da transaminase glutâmica oxalacética (TGO) (0,10>p>0,05) e aumento da área gástrica com alterações morfológicas macroscópicas como o desaparecimento do pregueamento mucoso característico. CONCLUSÃO: A água gaseificada favoreceu o aumento da área gástrica com conseqüente desaparecimento macroscópico do pregueamento mucoso do órgão, que ocasionou alterações metabólicas da função hepática.

Growth and metabolism of pacu (Piaractus mesopotamicus Holmberg 1887) juveniles fed diets containing different protein, lipid and carbohydrate levels

To verify the potential of lipids and carbohydrates to spare dietary protein and to understand the intermediary metabolism of interaction of these nutrients in pacu juveniles, an experiment was carried out to evaluate pacu physiological and performance parameters. The experimental design was completely randomized with 12 treatments in a 2 x 2 x 3 factorial arrangement, consisting of diets containing two digestible protein levels (200 and 230 g kg(-1) PD), two lipid levels (40 and 80 g kg(-1)) and three carbohydrate levels (410, 460 and 500 g kg(-1)). Fish-fed 230 g kg(-1) digestable protein (DP) showed increased glycaemia, decreased hepatic glycogen, as well as a smaller intake index and better feed conversion ratio. The higher dietary lipid level (80 g kg(-1)) reduced protein intake and serum protein concentration, increased liver and body fat content, but did not affect growth. At a lipid level of 80 g kg(-1), the increase in dietary carbohydrate levels promoted greater weight gain (WG), crude protein intake (CPI) and better feed conversion ratio (FCR). For fish fed diets containing 40 g kg(-1) lipid, the best energy-productive values (EPV) were obtained at 460 g kg(-1) carbohydrate. Increased levels of the main nutrients in the diets reduced the levels of serum triglycerides, while the increase in energy concentration increased the hepatosomatic (HSI) and glycaemia index values. Pacu used lipids as effectively as carbohydrates in the maximization of protein usage, as long as dietary protein was at a level of 230 g kg(-1) DP. The physiological parameters indicated that the best balance between the DP, dietary lipid and carbohydrate levels within the ranged this trial was obtained at 230, 40 and 460 g kg(-1), respectively, without lower growth.

Effects of apolipoprotein B-100 on the metabolism of a lipid microemulsion model in rats

In previous studies, it was shown that lipid microemulsions resembling LDL (LDE) but not containing protein, acquire apolipoprotein E when injected into the bloodstream and bind to LDL receptors (LDLR) using this protein as ligand. Aiming to evaluate the effects of apolipoprotein (apo) B-100 on the catabolism of these microemulsions, LDE with incorporated apo B-100 (LDE-apoB) and native LDL, all labeled with radioactive lipids were studied after intraarterial injection into Wistar rats. Plasma decay curves of the labels were determined in samples collected over 10 h and tissue uptake was assayed from organs excised from the animals sacrificed 24 h after injection. LDE-apo B had a fractional clearance rate (FCR) similar to native LDL (0.40 and 0.33, respectively) but both had FCR pronouncedly smaller than LDE (0.56, P<0.01). Liver was the main uptake site for LDE, LDE-apoB, and native LDL, but LDE-apoB and native LDL had lower hepatic uptake rates than LDE. Pre-treatment of the rats with 17 alpha-ethinylestradiol, known to upregulate LDLR, accelerated the removal from plasma of both LDE and LDE-apoB, but the effect was greater upon LDE than LDE-apoB. These differences in metabolic behavior documented in vivo can be interpreted by the lower affinity of LDLR for apo B-100 than for apo E, demonstrated in in vitro studies. Therefore, our study shows in vivo that, in comparison with apo E, apo B is a less efficient ligand to remove lipid particles such as microemulsions or lipoproteins from the intravascular compartment. (C) 1999 Elsevier B.V. B.V. All rights reserved.

Effects of monocrotaline on energy metabolism in the rat liver

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of a meal feeding schedule on hepatic glycogen synthesis and gluconeogenesis in rats

We investigated the effect of a meal feeding schedule (MFS) on food intake, hepatic glycogen synthesis, hepatic capacity to produce glucose and glycemia in rats. The MFS comprised free access to food for a 2-hour period daily at a fixed mealtime (8.00-10.00 a.m.) for 13 days. The control group was composed of rats with free access to food from day 1 to 12, which were then starved for 22 h, refed with a single meal at 8.00-10.00 a.m. and starved again for another 22 h. All experiments were performed at the meal time (i.e. 8.00 a.m.). The MFS group exhibited increased food intake and higher glycogen synthase activity. Since gluconeogenesis from L-glutamine or L-alanine was not affected by MFS, we conclude that the increased food intake and higher glycogen synthase activity contributed to the better glucose maintenance showed by MFS rats at the fixed meal time. Copyright © 2001 National Science Council, ROC and S. Karger AG, Basel.

Hepatic gluconeogenesis in rats trained to eat a single meal daily. Role of eating periodicity and the amount of food ingested in the last meal

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Toxicity of hypercaloric diet and monosodium glutamate: oxidative stress and metabolic shifting in hepatic tissue.

The present study examines the effects of a hypercaloric diet on hepatic glucose metabolism of young rats, with and without monosodium glutamate (MSG) administration, and the association of these treatments with evaluating markers of oxidative stress. Male weaned Wistar rats (21 days old) from mothers fed with a hypercaloric diet or a normal diet, were divided into four groups (n=6): control (C) fed with control diet; (MSG) treated with MSG (4 mg/g) and control diet; (HD) fed with hypercaloric diet and (MSG-HD) treated with MSG and HD. Rats were sacrificed after the oral glucose tolerance test (OGTT), at 45 days of treatments. Serum was used for insulin determination. Glycogen, hexokinase(HK), glucose-6-phosphatase(G6PH), lipid hydroperoxide, superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) were determined in liver. HD rats showed hypoglycemia, hyperinsulinemia, and high hepatic glycogen, HK and decreased G6PH. MSG and MSG-HD had hyperinsulinemia, hyperglycemia, decreased HK and increased G6PH in hepatic tissue. These animals had impaired OGTT. HD, MSG and MSG-HD groups had increased lipid hydroperoxide and decreased SOD in hepatic tissue. Hypercaloric diet and monosodium glutamate administration induced alterations in metabolic rate of glucose utilization and decreased antioxidant defenses. Therefore, the hepatic glucose metabolic shifting induced by HD intake and MSG administration were associated with oxidative stress in hepatic tissue.

Chronic alcohol intake upregulates hepatic expression of carotenoid cleavage enzymes and PPAR in rats

Excessive and chronic alcohol intake leads to a lower hepatic vitamin A status by interfering with vitamin A metabolism. Dietary provitamin A carotenoids can be converted into vitamin A mainly by carotenoid 15,15′-monooxygenase 1 (CMO1) and, to a lesser degree, carotenoid 9′10′-monooxygenase 2 (CMO2). CMO1 has been shown to be regulated by several transcription factors, such as the PPAR, retinoid X receptor, and thyroid receptor (TR). The regulation of CMO2 has yet to be identified. The impact of chronic alcohol intake on hepatic expressions of CMO1 and CMO2 and their related transcription factors are unknown. In this study, Fischer 344 rats were pair-fed either a liquid ethanol Lieber-DeCarli diet (n = 10) or a control diet (n = 10) for 11 wk. Hepatic retinoid concentration and expressions of CMO1, CMO2, PPARγ, PPARα, and TRβ as well as plasma thyroid hormones levels were analyzed. We observed that administering alcohol decreased hepatic retinoid levels but increased mRNA concentrations of CMO1, CMO2, PPARγ, PPARα, and TRβ and upregulated protein levels of CMO2, PPARγ, and PPARα. There was a positive correlation of PPARγ with CMO1(r = 0.89; P<0.0001) and both PPARγ and PPARα with CMO2 (r = 0.72, P< 0.001 and r = 0.62, P< 0.01, respectively). Plasma thyroid hormone concentrations did not differ between the control rats and alcohol-fed rats. This study suggests that chronic alcohol intake significantly upregulates hepatic expression of CMO1 and, to a much lesser extent, CMO2. This process may be due to alcohol-induced PPARγ expression and lower vitamin A status in the liver. © 2010 American Society for Nutrition.

Short communication: Acute but transient increase in serum insulin reduces messenger RNA expression of hepatic enzymes associated with progesterone catabolism in dairy cows

The objective of this experiment was to evaluate the effects of glucose infusion on serum concentrations of glucose, insulin, and progesterone (P4), as well as mRNA expression of hepatic CYP2C19 and CYP3A4 in nonlactating, ovariectomized cows in adequate nutritional status. Eight Gir × Holstein cows were maintained on a low-quality Brachiaria brizantha pasture with reduced forage availability, but they individually received, on average, 3. kg/cow daily (as fed) of a corn-based concentrate from d -28 to 0 of the experiment. All cows had an intravaginal P4-releasing device inserted on d -14, which remained in cows until the end of the experiment (d 1). On d 0, cows were randomly assigned to receive, in a crossover design containing 2 periods of 24. h each (d 0 and 1), (1) an intravenous glucose infusion (GLUC; 0.5. g of glucose/kg of BW, over a 3-h period) or (2) an intravenous saline infusion (SAL; 0.9%, over a 3-h period). Cows were fasted for 12. h before infusions, and they remained fasted during infusion and sample collections. Blood samples were collected at 0, 3, and 6. h relative to the beginning of infusions. Liver biopsies were performed concurrently with blood collections at 0 and 3. h. After the last blood collection of period 1, cows received concentrate and returned to pasture. Cows gained BW (16.5 ± 3.6. kg) and BCS (0.08 ± 0.06) from d -28 to 0. Cows receiving GLUC had greater serum glucose and insulin concentrations at 3. h compared with SAL cohorts. No treatment effects were detected for serum P4 concentrations, although mRNA expression of CYP2C19 and CYP3A4 after the infusion period was reduced for cows in the GLUC treatment compared with their cohorts in the SAL treatment. In conclusion, hepatic CYP3A4 and CYP2C19 mRNA expression can be promptly modulated by glucose infusion followed by acute increases in circulating insulin, which provides novel insight into the physiological mechanisms associating nutrition and reproductive function in dairy cows. © 2013 American Dairy Science Association.

Moderate physical activity from childhood contributes to metabolic health and reduces hepatic fat accumulation in adult rats

Background: Obesity, oxidative stress and inflammation, by triggering insulin resistance, may contribute to the accumulation of hepatic fat, and this accumulation by lipotoxicity can lead the organ to fail. Because obesity is growing at an alarming rate and, worryingly, in a precocious way, the present study aimed to investigate the effects of moderate physical training performed from childhood to adulthood on liver fat metabolism in rats. Methods. Twenty rats that were 28days old were divided into two groups: control (C) and trained (T). The C Group was kept in cages without exercise, and the T group was submitted to swimming exercise for 1hour/day, 5days/week from 28 to 90days of age (8weeks) at 80% of the anaerobic threshold determined by the lactate minimum test. At the end of the experiment, the body weight gain, insulin sensitivity (glucose disappearance rate during the insulin tolerance test), concentrations of free fatty acids (FFA) and triglycerides (TG) and hepatic lipogenic rate were analyzed. For the statistical analysis, the Student t-test was used with the level of significance preset at 5%. Results: The T group showed lower body weight gain, FFA concentrations, fat accumulation, hepatic lipogenic rate and insulin resistance. Conclusion: The regular practice of moderate physical exercise from childhood can contribute to the reduction of obesity and insulin resistance and help prevent the development of accumulation of hepatic fat in adulthood. © 2013de Moura et al; licensee BioMed Central Ltd.

Lipid metabolism of commercial layers fed diets containing aflatoxin, fumonisin, and a binder

Aflatoxins (AF) and fumonisins (FU) are a major problem faced by poultry farmers, leading to huge economic losses. This experiment was conducted to determine the effects of AF (1 mg/kg of feed) and FU (25 mg/kg of feed), singly or in combination, on the lipid metabolism in commercial layers and investigate the efficacy of a commercial binder (2 kg/t of feed) on reducing the toxic effects of these mycotoxins. A total of 168 Hisex Brown layer hens, 37 wk of age, were randomized into a 3 × 2 + 1 factorial arrangement (3 diets with no binder containing AF, FU, and AF+FU; 3 diets with binder containing AF, FU, and AF+FU; and a control diet with no mycotoxins and binders), totaling 7 treatments. The hens contaminated with AF showed the characteristic effects of aflatoxicosis, such as a yellow liver, resulting from the accumulation of liver fat, lower values of plasma very low-density lipoprotein and triglycerides, and higher relative weight of the kidneys and liver. Hepatotoxic and nephrotoxic effects of FU were not observed in this study. On the other hand, the FU caused a reduction in small intestine length and an increase in abdominal fat deposition. The glucan-based binder prevented some of the deleterious effects of these mycotoxins, particularly the effects of AF on hepatic lipid metabolism, kidney relative weight, and FU in the small intestine. © 2013 Poultry Science Association Inc.

Evaluation of mutagenicity and metabolism-mediated cytotoxicity of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin from Paepalanthus latipes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Fructose-Induced Hypothalamic AMPK Activation Stimulates Hepatic PEPCK and Gluconeogenesis due to Increased Corticosterone Levels

Fructose consumption causes insulin resistance and favors hepatic gluconeogenesis through mechanisms that are not completely understood. Recent studies demonstrated that the activation of hypothalamic 5'-AMP-activated protein kinase (AMPK) controls dynamic fluctuations in hepatic glucose production. Thus, the present study was designed to investigate whether hypothalamic AMPK activation by fructose would mediate increased gluconeogenesis. Both ip and intracerebroventricular (icv) fructose treatment stimulated hypothalamic AMPK and acetyl-CoA carboxylase phosphorylation, in parallel with increased hepatic phosphoenolpyruvate carboxy kinase (PEPCK) and gluconeogenesis. An increase in AMPK phosphorylation by icv fructose was observed in the lateral hypothalamus as well as in the paraventricular nucleus and the arcuate nucleus. These effects were mimicked by icv 5-amino-imidazole-4-carboxamide-1-beta-D-ribofuranoside treatment. Hypothalamic AMPK inhibition with icv injection of compound C or with injection of a small interfering RNA targeted to AMPK alpha 2 in the mediobasal hypothalamus (MBH) suppressed the hepatic effects of ip fructose. We also found that fructose increased corticosterone levels through a mechanism that is dependent on hypothalamic AMPK activation. Concomitantly, fructose-stimulated gluconeogenesis, hepatic PEPCK expression, and glucocorticoid receptor binding to the PEPCK gene were suppressed by pharmacological glucocorticoid receptor blockage. Altogether the data presented herein support the hypothesis that fructose-induced hypothalamic AMPK activation stimulates hepatic gluconeogenesis by increasing corticosterone levels. (Endocrinology 153: 3633-3645, 2012)