Partial rescue of retinal function in chronically hypoglycemic mice

Purpose. Mice rendered hypoglycemic by a null mutation in the glucagon receptor gene Gcgr display late-onset retinal degeneration and loss of retinal sensitivity. Acute hyperglycemia induced by dextrose ingestion does not restore their retinal function, which is consistent with irreversible loss of vision. The goal of this study was to establish whether long-term administration of high dietary glucose rescues retinal function and circuit connectivity in aged Gcgr−/− mice. Methods. Gcgr−/− mice were administered a carbohydrate-rich diet starting at 12 months of age. After 1 month of treatment, retinal function and structure were evaluated using electroretinographic (ERG) recordings and immunohistochemistry. Results. Treatment with a carbohydrate-rich diet raised blood glucose levels and improved retinal function in Gcgr−/− mice. Blood glucose increased from moderate hypoglycemia to euglycemic levels, whereas ERG b-wave sensitivity improved approximately 10-fold. Because the b-wave reflects the electrical activity of second-order cells, we examined for changes in rod-to-bipolar cell synapses. Gcgr−/− retinas have 20% fewer synaptic pairings than Gcgr+/− retinas. Remarkably, most of the lost synapses were located farthest from the bipolar cell body, near the distal boundary of the outer plexiform layer (OPL), suggesting that apical synapses are most vulnerable to chronic hypoglycemia. Although treatment with the carbohydrate-rich diet restored retinal function, it did not restore these synaptic contacts. Conclusions. Prolonged exposure to diet-induced euglycemia improves retinal function but does not reestablish synaptic contacts lost by chronic hypoglycemia. These results suggest that retinal neurons have a homeostatic mechanism that integrates energetic status over prolonged periods of time and allows them to recover functionality despite synaptic loss.

Role of dietary fibers in the nutritional management of hyperuricemia

Foods rich in adenine and hypoxanthine may contribute to the increase of uricemia. Hyperuricemia is associated with other pathological conditions pertaining to metabolic syndrome. Objective: the assessement of the impact of fiber rich diet on uricemia in patients with metabolic syndrome. Methods: the study involved 46 male patients with metabolic syndrome who claimed to have reduced mobility in fingers, hypertension, obesity, hyperglycemia and hyperuricemia. A validated questionnaire about dietary habits was applied at the beginning of the study and after 6 weeks of fiber-rich diet by eliminating from patients diet preparations of animal food and increased intake of vegetable foods. Blood presure, body mass index, blood glucose and uric acids were measured at the beginning of the study and after 6 weeks of fiber rich diet by daily consumption of 2 servings of added grains - 60g totally and vegetables 200g, fruits 300g respectively. Results: The study shows that at baseline all patients had an inadequate dietary intake of dietary fiber, 28.5 ± 2.2 g/day instead of 38 g per day.The increase in fiber intake of 10 ± 5 g/day was associated with a decrease of serum uric acid by 69.87% from 8.3  0.6 mg/dL to 5.8  0.5 mg/dL, p = 0.008, non-significant decrease of BMI (from 26.8  4.5 to 26.4  4.6 kg/m2, p<0.01), significant decrease of glycemia (from 130  0.8 to 105  4.2mg/dL, p <0.001) and significant decrease in blood pressure (from 150  10.6 to 130  8.4 mmHg, p <0.001). Conclusion: The fiber rich diet decreased blood uric acid, blood glucose levels an arterial pressure in patients with metabolic syndrome.

Fructose Alters Adiponectin, Haptoglobin and Angiotensinogen Gene Expression in 3T3-L1 Adipocytes

Fructose- or sucrose-rich diets can cause insulin resistance and increase the risk of cardiovascular disease. Adipokines are correlated with the development of these diseases in obesity. We hypothesize that fructose and sucrose induce insulin resistance via effects on adipokine gene expression in adipocytes. This study analyzed the effect of fructose or glucose on adiponectin, haptoglobin, and angiotensinogen gene expression in 3T3-L1 adipocytes. Ten days after differentiation, the cells were pretreated with serum- and glucose-free medium. Twenty-four hours later, fructose or glucose (0, 5, 10, or 20 mmol) was added into the medium, and the cells were collected after a further 24 hours. Adiponectin, haptoglobin, and angiotensinogen gene expression were determined. Adiponectin gene expression increased when 10 or 20 mmol glucose was added compared with that observed for the non–hexose-treated cells. A similar effect occurred when 5 mmol fructose was added. Glucose (10 mmol) and fructose (20 mmol) stimulated haptoglobin gene expression in 3T3-L1 adipocytes compared with 0 mmol, with glucose producing a more pronounced effect. Although 20 mmol fructose caused an increase in angiotensinogen gene expression, glucose did not. In conclusion, in this study of 2 hexoses revealed an increase in adiponectin gene expression, suggesting that the effect of a glucose-rich diet on the development of insulin resistance is not related to the effect of these hexoses on adipocyte adiponectin gene expression. However, insulin resistance and cardiovascular disease promoted by fructose-rich diets could be partially related to the effect of fructose on adiponectin and angiotensinogen gene expression.

Efeito do sistema de produção nas características físico-químicas e no perfil lipídico de três músculos de suínos alentejanos

O presente trabalho tem como objetivo testar o efeito do sistema de produção com dieta rica em ácido oleico nas características zootécnicas, de carcaça, físico-químicas e no perfil lipídico dos músculos Longissimus dorsi (LD), Biceps femoris (BF) e Semimembranosus (SM) de suínos de raça Alentejana. Foram utilizados 15 animais, divididos em dois grupos, o grupo IN (n=9) foi mantido em parques individuais abertos ao exterior com 3 m2 e o grupo OUT (n=6) foi mantido numa área de 3 ha com acesso a pastagem. O grupo OUT obteve melhores performances zootécnicas. O rendimento de carcaça foi igual para ambos os grupos, e o rendimento comercial e proporção de peças nobres foi superior nos OUT. Estes obtiveram menores teores de lípidos intramusculares mas maiores teores de PUFA (ácidos gordos polinsaturados) e melhores valores para os rácios PUFA/SFA (ácido gordos saturados) e n-6/n-3. O SM foi menos afetado pelo sistema de produção; Abstract: Effect of the rearing system in the physical-chemical characteristics and the lipid profile of three muscles from Alentejano pigs The present study aims to test the effect of rearing system with oleic acid rich diet on performance, carcass and physical-chemical characteristics, and lipid profile of the muscles Longissimus dorsi (LD), Biceps femoris (BF) and Semimembranosus (SM) from Alentejano pigs. The study used 15 animals, divided into two groups. The Group IN (n = 9) was kept in individual parks open to the exterior with 3 m2, and the OUT (n = 6) was held in an area of 3 ha with access to pasture. The OUT group obtained the best performances. The carcass yield was the same for both groups, meat yield and the proportion of noble parts was superior in the OUT. These obtained lower levels of intramuscular fat but larger PUFA levels (polyunsaturated fatty acids) and best values for the ratios PUFA/SFA (saturated fatty acids) and n-6/n-3. The SM was the least affected by the rearing system

Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 5580 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function.We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.1511.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.0100.316) and 0.294 (0.0550.534), respectively];walnuts with working memory [1.191 (0.0612.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.0060.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.2362.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.

Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 55-80 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function.We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.151-1.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.010-0.316) and 0.294 (0.055-0.534), respectively];walnuts with working memory [1.191 (0.061-2.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.006-0.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.236-2.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.

Diet rich in high glucoraphanin broccoli reduces plasma LDL cholesterol: evidence from randomised controlled trials

Cruciferous-rich diets have been associated with reduction in plasma LDL-cholesterol (LDL-C), which may be due to the action of isothiocyanates derived from glucosinolates that accumulate in these vegetables. This study tests the hypothesis that a diet rich in high glucoraphanin (HG) broccoli will reduce plasma LDL-C. METHODS AND RESULTS: One hundred and thirty volunteers were recruited to two independent double-blind, randomly allocated parallel dietary intervention studies, and were assigned to consume either 400 g standard broccoli or 400 g HG broccoli per week for 12 weeks. Plasma lipids were quantified before and after the intervention. In study 1 (37 volunteers), the HG broccoli diet reduced plasma LDL-C by 7.1% (95% CI: -1.8%, -12.3%, p = 0.011), whereas standard broccoli reduced LDL-C by 1.8% (95% CI +3.9%, -7.5%, ns). In study 2 (93 volunteers), the HG broccoli diet resulted in a reduction of 5.1% (95% CI: -2.1%, -8.1%, p = 0.001), whereas standard broccoli reduced LDL-C by 2.5% (95% CI: +0.8%, -5.7%, ns). When data from the two studies were combined the reduction in LDL-C by the HG broccoli was significantly greater than standard broccoli (p = 0.031). CONCLUSION: Evidence from two independent human studies indicates that consumption of high glucoraphanin broccoli significantly reduces plasma LDL-C

Urinary metabolomic profiling to identify biomarkers of a flavonoid-rich and flavonoid-poor fruits and vegetables diet: the FLAVURS trial in adults: the FLAVURS trial

The present study aims to investigate the dose dependent effects of consuming diets enriched in flavonoid-rich and flavonoid-poor fruits and vegetables on the urine metabolome of adults who had a C1.5 fold increased risk of cardiovascular diseases. A single-blind, dose-dependent, parallel randomized controlled dietary intervention was conducted where volunteers (n = 126) were randomly assigned to one of three diets: high flavonoid diet, low flavonoid diet or habitual diet as a control for 18 weeks. High resolution LC– MS untargeted metabolomics with minimal sample cleanup was performed using an Orbitrap mass spectrometer. Putative biomarkers which characterize diets with high and low flavonoid content were selected by state-of-the-art data analysis strategies and identified by HR-MS and HR-MS/MS assays. Discrimination between diets was observed by application of two linear mixedmodels: one including a diet-time interaction effect and the second containing only a time effect. Valerolactones, phenolic acids and their derivatives were among sixteen biomarkers related to the high flavonoid dietary exposure. Four biomarkers related to the low flavonoid diet belonged to the family of phenolic acids. For the first time abscisic acid glucuronide was reported as a biomarker after a dietary intake, however its origins have to be examined by future hypothesis driven experiments using a more targeted approach. This metabolomic analysis has identified a number of dose dependent urinary biomarkers (i.e. proline betaine or iberin-N-acetyl cysteine), which can be used in future observation and intervention studies to assess flavonoids and nonflavonoid phenolic intakes and compliance to fruit and vegetable intervention.

Could a high-fat diet rich in unsaturated fatty acids impair the cardiovascular system?

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

Decaffeinated green tea extract rich in epigallocatechin-3-gallate improves insulin resistance and metabolic profiles in normolipidic diet--but not high-fat diet-fed mice

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Green tea extract rich in epigallocatechin-3-gallate prevents fatty liver by ampk activation via lkb1 in mice fed a high-fat diet

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

Modulation of plasma levels and percentages of incorporation of ω-3 PUFAs in egg yolk under the influence of supplementation sources rich in omega 3 to diet of laying

Hundred forty-four Shaver White laying hens were used over a 4 week experimental period to investigate the effect of 3% of soybean oil, corn oil (MIL), canola oil, flaxseed oil (LIN), salmon oil (SAL) or tuna and sardine oil (SR/AT) added to the diets, upon the fatty acid egg yolk composition, blood plasma levels and incorporation time of each fatty acid into the egg yolk. Hens were allocated into 72 cages and the experimental design was a 6 x 6 randomized factorial model. Hens fed 3% of different oils, responded with increased polyunsaturated fatty acids omega 3 (ω-3 PUFAs), except for corn oil. The addition of flaxseed, soybean or corn oil into the diet increased the PUFAs levels into the egg yolk and in the blood plasma. Adding tuna and sardine oil into the diet increased the concentration of yolk saturated fatty acids. The levels of ω-3 PUFAs were increased in the tuna and sardine oil treatment, while the flaxseed oil increased the plasma fatty acids. The deposition of 349.28 mg/yolk of a-linolenic fatty acids (ALA) was higher in the group fed LIN, while the higher equal to 157.13 mg DHA/yolk was observed in group SR/AT. In the plasma, deposition increased from 0.33% (MIL) for 6.29% ALA (LIN), while that of DHA increase of 0.47% (MIL) for 4.24% (SAL) and 4.48% (SR/AT) and of 0.98% (MIL) for 6.14% (SR/AT) and 8.44% (LIN) of ω-3 PUFAs. The percentage of EPA into the yolk and plasma was higher for the hens fed 3% tuna and sardine oil diet, as well as the levels of yolk DHA. The concentration of DHA into the plasma was higher for the salmon and tuna/sardine oil treatments. The PUFAs yolk decreased during the first eight days of experiment, while the ω-3 PUFAs increased during the same period. The concentration of ALA increased until ten days of experiment, while the percentage of EPA and DHA increased up to the eighth experimental day

Lipid profile of the yolk under the influence of supplementaries sources rich in Ω-3 PUFAs in the diet of laying hens in the time

Two hundred eighty-eight 32-wk-old Hisex White laying hens were used in this research during a 10 weeks period, arranged in a 2 x 5 completely randomized factorial design, with three replicates of eight birds per treatment. Two groups: fish oil (OP) and Marine Algae (AM) with five DHA levels (120, 180, 240, 300 and 360 mg/100 g diet) were assigned including two control groups birds fed corn and soybean basal diet (CON) and a diet supplemented with AM (AM420) to study the effect of time 0, 2, 4, 6 and 8 weeks (wk) on the efficiency of egg yolk fatty acid enrichment. The means varied (p<0.01) of 17.63% (OP360) to 22.08% (AM420) is the total Polyunsaturated Fatty Acids (PUFAs) and 45.8 mg/g (OP360), 40.37 mg/g (OP360, 4 wk) to 65.82 mg/g (AM420) and 68.79 mg/g/yolk (AM120, 8 wk) for n-6 PUFAs. On the influence of sources and levels in the times, the means of n-3 PUFAs increased by 5.58 mg/g (AM120, 2 wk) to 14.16 mg/g (OP360, 6 wk) when compared to average of 3.34 mg PUFAs Ω/g/yolk (CON). Usually, the means DHA also increased from 22.34 (CON) to 176.53 mg (μ, OP360), 187.91 mg (OP360, 8 wk) and 192.96 mg (OP360, 6 wk) and 134.18 mg (μ, OP360), 135.79 mg (AM420, 6 wk), 149.75 mg DHA (AM420, 8 wk) per yolk. The opposite was observed for the means AA, so the effect of the sources, levels and times, decreased (P <0.01) of 99.83 mg (CON) to 31.99 mg (OP360, 4 wk), 40.43 mg (μ, OP360) to 61.21 mg (AM420) and 71.51 mg AA / yolk (μ, AM420). Variations of the average weight of 15.75g (OP360) to 17.08g (AM420) yolks of eggs de 32.55% (AM420) to 34.08% (OP360) of total lipids and 5.28 g (AM240) to 5.84 g (AM120) of fat in the yolk were not affected (p>0.05) by treatments, sources, levels and times studied. Starting of 2 week, the hens increased the level of n-3 PUFAs in the egg yolks, being expressively increased (p<0.01) until 4 weeks, which after the increased levels of n-3 PUFAs tended to if stabilize around of time of 8 experimental weeks, when it was more effective saturation of the tissues and yolk.

Magnesium-deficient High-fat Diet: Effects On Adiposity, Lipid Profile And Insulin Sensitivity In Growing Rats.

To determine if magnesium deficiency aggravates the effects of a high-fat diet in growing rats in terms of obesity, lipid profile and insulin resistance. The study population comprised 48 newly weaned male Wistar Hannover rats distributed into four groups according to diet, namely, control group (CT; n = 8), control diet provided ad libitum; pair-feeding control group (PF; n = 16), control diet but in the same controlled amount as animals that received high-fat diets; high-fat diet group (HF; n = 12), and magnesium-deficient high-fat diet group (HFMg(-); n = 12). The parameters investigated were adiposity index, lipid profile, magnesium status, insulin sensitivity and the phosphorylation of proteins involved in the insulin-signaling pathway, i.e. insulin receptor β-subunit, insulin receptor substrate 1 and protein kinase B. The HF and HFMg(-) groups were similar regarding gain in body mass, adiposity index and lipid profile, but were significantly different from the PF group. The HFMg(-) group exhibited alterations in magnesium homeostasis as revealed by the reduction in urinary and bone concentrations of the mineral. No inter-group differences were observed regarding glucose homeostasis. Protein phosphorylation in the insulin-signaling pathway was significantly reduced in the high-fat groups compared with the control groups, demonstrating that the intake of fat-rich diets increased insulin resistance, a syndrome that was aggravated by magnesium deficiency. Under the experimental conditions tested, the intake of a magnesium-deficient high-fat diet led to alterations in the insulin-signaling pathway and, consequently, increased insulin resistance.

Paclitaxel associated with cholesterol-rich nanoemulsions promotes atherosclerosis regression in the rabbit

A cholesterol-rich nanoemulsion (LDE) that resembles LDL binds to the LDL receptors and after injection into the blood stream may concentrate in cells with LDL receptor overexpression, as occurs in neoplasias and other proliferative processes. Thus, LDE can be used as vehicle to target drugs against those cells. The current study was designed to verify in rabbits whether LDE concentrates in the lesioned rabbit artery and whether a paclitaxel derivative, paclitaxel oleate, associated to LDE could reduce the atherosclerotic lesions. Sixteen male New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30 under cholesterol feeding, eight animals were treated with four weekly intravenous injections of LDE-paclitaxel (4 mg/kg) and eight with four weekly intravenous saline solution injections for additional 30 days. On day 60, the animals were sacrificed for analysis. The uptake of LDE labeled with [C-14]-cholesteryl oleate by the aortic arch of cholesterol-fed rabbits was twice as much that observed in animals fed only regular chow. LDE-paclitaxel reduced the lesion areas of cholesterol-fed animals by 60% and intima-media ratio fourfold and inhibited the macrophage migration and the smooth muscle cell proliferation and invasion of the intima. LDE-paclitaxel treatment had no toxicity. In conclusion, LDE-paclitaxel produced pronounced atherosclerosis regression without toxicity and has shown remarkable potential in cardiovascular therapeutics. (c) 2008 Published by Elsevier Ireland Ltd.