Dietary saponins of sea cucumber alleviate orotic acid-induced fatty liver in rats via PPARα and SREBP-1c signaling

Background  

Nonalcoholic fatty liver disease is the most common chronic liver disease in the world, and is becoming increasingly prevalent. Saponins of sea cucumber (SSC) are proven to exhibit various biological activities. Therefore, the present study was undertaken to examine the effect of saponins extracted from sea cucumber (Pearsonothuria graeffei) on the preventive activity of fatty liver in rats.     

Discovery of gemfibrozil analogues that activate PPARα and enhance the expression of gene CPT1A involved in fatty acids catabolism

A new series of gemfibrozil analogues conjugated with α-asarone, trans-stilbene, chalcone, and their bioisosteric modifications were synthesized and evaluated to develop PPARα agonists. In this attempt, we have removed the methyls on the phenyl ring of gemfibrozil and introduced the above scaffolds in para position synthesizing two series of derivatives, keeping the dimethylpentanoic skeleton of gemfibrozil unaltered or demethylated. Four compounds exhibited good activation of the PPARα receptor and were also screened for their activity on PPARα-regulated gene CPT1A.     

Dietary d-limonene alleviates insulin resistance and oxidative stress–induced liver injury in high-fat diet and L-NAME-treated rats

Background  

Nonalcoholic fatty liver disease (NAFLD) is one of the most common etiologies of chronic liver disease worldwide. The pathogenesis of metabolic syndrome associated with NAFLD is still under debate.     

Dietary supplementation with geranylgeraniol suppresses lipopolysaccharide-induced inflammation via inhibition of nuclear factor-κB activation in rats

Purpose

The isoprenoid geranylgeraniol (GGOH) inhibits nuclear factor-kappa B (NF-κB) activation in the liver, yet the mechanism remains unclear. We investigated the modulation and inhibition of lipopolysaccharide (LPS)-induced NF-κB signaling in the liver of rats fed a GGOH-supplemented diet.

Methods

Rats were fed a diet supplemented with or without GGOH for 10 days. Rats were then intraperitoneally injected with 0.5 mg/kg LPS or vehicle (sterilized saline) and fasted for 18 h. Plasma levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and the liver damage indicators alanine and aspartate aminotransferases (ALT and AST) were assessed. Liver mRNA and proteins were assayed for changes in NF-κB target genes and signal transduction genes.

Results

Rats fed a high-dose, GGOH-supplemented diet showed significantly lower levels of plasma inflammatory cytokines and ALT and AST activities. In the liver, GGOH significantly suppressed NF-κB activation and mRNA expression of its pro-inflammatory target genes. Furthermore, GGOH supplementation substantially suppressed mRNA expression of signal transducer genes upstream of the IκB kinase complex. Western blotting of liver extracts further demonstrated the substantial decrease in total IL-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6), leading to lower signal transduction and inhibition of NF-κB after LPS.

Conclusion

A 10-day, high-dose, GGOH-supplemented diet was sufficient to inhibit LPS-induced inflammation and activation of NF-κB in rat livers. GGOH significantly modulated NF-κB signaling molecules, inhibiting its signal transduction and activation in the liver, thus protecting against liver damage.     

Serum and liver lipids in rats fed mixtures of corn and palm oils ± cholesterol

Rats were fed diets containing various mixtures of corn and palm oils ranging from 100% corn (CO) or palm oil (PO) to 90:10, 75:25, or 50:50 CO, and 75:25, 10:90, or 100% PO. One set of diets was augmented with 0.4% cholesterol and 0.1% cholic acid. When the diets were cholesterol-free, there were virtually no differences between groups in serum total or HDL cholesterol. Serum triglyceride levels were lowest in the rats fed 100% PO. Liver cholesterol levels were virtually the same in all groups. As the PO contribution to the dietary fat was increased, liver triglyceride levels fell, being lowest in rats fed 100% PO. Serum total and HDL cholesterol levels in rats fed CO plus cholesterol-cholic acid were the same as those seen in rats on the cholesterol-free diet. Introduction of the lowest level of PO raised serum cholesterol levels significantly and they continued to rise as more palm oil (palmitic acid) was introduced into the diet. Serum triglyceride levels were similar in all groups, but liver triglycerides fell with increasing dietary PO.The data support the assertion of Hayes and Khosla that palmitic acid becomes hypercholesterolemic only in cholesterol-containing diets. The observed effects of palmitic acid on serum and liver triglyceride levels, especially the latter, merit further study.     

Combined effect of sesamin and α-lipoic acid on hepatic fatty acid metabolism in rats

Purpose

Dietary sesamin (1:1 mixture of sesamin and episesamin) decreases fatty acid synthesis but increases fatty acid oxidation in rat liver. Dietary α-lipoic acid lowers hepatic fatty acid synthesis. These changes can account for the serum lipid-lowering effect of sesamin and α-lipoic acid. It is expected that the combination of these compounds in the diet potentially ameliorates lipid metabolism more than the individual compounds. We therefore studied the combined effect of sesamin and α-lipoic acid on lipid metabolism in rats.

Methods

Male Sprague–Dawley rats were fed diets supplemented with 0 or 2 g/kg sesamin and containing 0 or 2.5 g/kg α-lipoic acid for 22 days.

Results and conclusions

Sesamin and α-lipoic acid decreased serum lipid concentrations and the combination of these compounds further decreased the parameters in an additive fashion. These compounds reduced the hepatic concentration of triacylglycerol, the lignan being less effective in decreasing this value. The combination failed to cause a stronger decrease in hepatic triacylglycerol concentration. The combination of sesamin and α-lipoic acid decreased the activity and mRNA levels of hepatic lipogenic enzymes in an additive fashion. Sesamin strongly increased the parameters of hepatic fatty acid oxidation enzymes. α-Lipoic acid antagonized the stimulating effect of sesamin of fatty acid oxidation through reductions in the activity of some fatty acid oxidation enzymes and carnitine concentration in the liver. This may account for the failure to observe strong reductions in hepatic triacylglycerol concentration in rats given a diet containing both sesamin and α-lipoic acid.     

Hepatic lipid metabolism response to dietary fatty acids is differently modulated by PPARα in male and female mice

Background  

In human beings, women are at lower risk of cardiovascular diseases, and respond differently from men to dietary fatty acids.     

Dietary supplementation of GrandFusion® mitigates cerebral ischemia-induced neuronal damage and attenuates inflammation

Objectives: Dietary supplementation of fruits and vegetables has been the main stay for nutritional benefit and overall well-being. GrandFusion^® is a nutritional supplement that contains the natural nutrients from whole fruits and vegetables that include complex nutrients and phytonutrients that contain anti-oxidant, anti-inflammatory, and neuroprotective properties.

Methods: In this study, C57BL/6 mice were fed a diet supplemented with GrandFusion^® for 2 months prior to 1 hour of ischemia induced by occlusion of the middle cerebral artery (MCAo) followed by various times of reperfusion. Mice were subjected to MCAo for 1 hour and then at various times following reperfusion, animals were assessed for behavioral outcomes (open field testing, rotarod, and adhesive test removal), and infarct volumes (cresyl violet and triphenyltetrazolium chloride). In addition, to determine the potential mechanisms associated with treatment, the brain tissue was examined for changes in oxidative stress and inflammatory markers.

Results: The GrandFusion^® diet was able to show a significant protection from infarct damage in the brain and an improvement in neurological outcomes. The diet did not alter heart rate, blood pressure, pO₂, pCO₂, or pH. In addition, the diet mitigated inflammation by reducing microglial and astrocytic activation following ischemia and reperfusion and limiting oxidative stress.

Discussion: The study demonstrates the neuroprotective effect of a diet rich in fruits and vegetables that contain anti-oxidant and anti-inflammatory against the impact of cerebral ischemia and reperfusion injury.     

Wheat aleurone fractions and plasma n−3 fatty acids in rats

Abstract

The main aim of this study was to compare the effects of two wheat aleurone (WA) fractions on circulating n?3 fatty acids in rats. We demonstrated that only the fraction able to induce the highest urinary excretion of polyphenol metabolites (>1µmol) resulted in a significant increase in plasma level of Eicosapentanoic acid (+22%, p?<?0.05). While other constituents of whole wheat can be involved in this response, our data suggest that cereals containing high levels of phenolic compounds can increase blood n?3 without affecting n?6 fatty acids. Further studies are required to confirm this hypothesis and explore the underlying biological mechanisms.     

Triiodothyronine stimulates VEGF expression and secretion via steroids and HIF-1α in murine Leydig cells

Leydig cells are the principal steroidogenic cells of the testis. Leydig cells also secrete a number of growth factors including vascular endothelial growth factor (VEGF) which has been shown to regulate both testicular steroidogenesis and spermatogenesis. The thyroid hormone, T_3, is known to stimulate steroidogenesis in Leydig cells. T₃ has also been shown to stimulate VEGF production in a variety of cell lines. However, studies regarding the effect of T₃ on VEGF synthesis and secretion by the Leydig cells were lacking. Therefore, we investigated the effect of T₃ on VEGF synthesis and secretion in a mouse Leydig tumour cell line, MLTC-1. The effect of T₃ was compared with that of LH/cAMP and hypoxia, two known stimulators of Leydig cell functions. The cells were treated with T₃, 8-Br-cAMP (a cAMP analogue), or CoCl₂ (a hypoxia mimetic) and VEGF secreted in the cell supernatant was measured using ELISA. The mRNA levels of VEGF were measured by quantitative RT-PCR. In the MLTC-1 cells, T₃, 8-Br-cAMP, and CoCl₂ stimulated VEGF mRNA levels and the protein secretion. T₃ also increased steroid secretion as well as HIF-1α protein levels, two well-established upstream regulators of VEGF. Inhibitors of steroidogenesis as well as HIF-1α resulted in inhibition of T₃-stimulated VEGF secretion by the MLTC-1 cells. This suggested a mediatory role of steroids and HIF-1α protein in T₃-stimulated VEGF secretion by MLTC-1 cells. The mediation by steroids and HIF-1α were independent of each other.

Abbreviations: 8-Br-cAMP: 8-bromo – 3?, 5? cyclic adenosine monophosphate; CoCl₂: cobalt chloride; HIF-1α: hypoxia inducible factor ?1α; LH: luteinizing hormone; T₃: 3, 5, 3?-L-triiodothyronine; VEGF: vascular endothelial growth factor     

Consumption of a high β-glucan barley flour improves glucose control and fatty liver and increases muscle acylcarnitines in the Zucker diabetic fatty rat

Purpose

The soluble fiber β-glucan, a natural component of barley, has been shown to lower the postprandial glucose response and is thought to improve insulin resistance.

Methods

This study examined the effect of chronic consumption of the high β-glucan barley flour on glucose control, liver lipids and markers of muscle fatty acid oxidation in the Zucker diabetic fatty (ZDF) rat. Two groups of ZDF rats were fed diets containing either 6 % β-glucan in the form of barley flour or cellulose as a control for 6 weeks. A group of Zucker lean rats served as a negative control.

Results

The barley flour group had an increased small intestinal contents viscosity compared to the obese control group. After 6 weeks, the barley flour group had reduced glycated hemoglobin, lower relative kidney weights and a reduced area under the curve during a glucose tolerance test, indicating improved glucose control. Fasting plasma adiponectin levels increased in the barley flour group and were not different than the lean control group. ZDF rats on the barley flour diet had lower relative epididymal fat pad weights than the obese control and a greater food efficiency ratio. The barley flour group also had reduced liver weights and a decreased concentration of liver lipids. The barley flour group had significantly higher concentrations of muscle acylcarnitines, a metabolite generated during fatty acid oxidation.

Conclusion

These results show that chronic consumption of β-glucans can improve glucose control and decrease fatty liver in a model of diabetes with obesity.     

Dietary eicosapentaenoic acid normalizes hippocampal omega-3 and 6 polyunsaturated fatty acid profile,attenuates glial activation and regulates BDNF function in a rodent model of neuroinflammation induced by central interleukin-1β administration

Purpose

Interleukin (IL)-1β can activate glial cells to trigger neuroinflammation and neurodegeneration. Lower omega (n)-3 polyunsaturated fatty acids (PUFAs) and lower n-3/n-6 PUFA ratios occur in the brain of patients with Alzheimer’s disease (AD). We have previously reported that an n-3 PUFA, eicosapentaenoic acid (EPA), can improve memory and attenuate neurodegeneration-like changes in animal models of AD. However, whether and how EPA modulates glial cell activity and functions remains unclear. The aim of this study was to test the hypothesis that EPA may attenuate neuroinflammation by inhibiting microglial activation and microglia-produced proinflammatory cytokines, and by enhancing the expression of astrocytes-produced neurotrophins and their receptors.

Methods

Male Long-Evans rats were fed either palm oil supplemented diet or EPA supplemented diet for 42 days. On day 36 of diet feeding, rats received an intracerebroventricular injection of IL-1β or saline for 7 days. The glial activation, the expression of amyloid precursor protein (APP), calcium-dependent phospholipase (cPL) A2, brain-derived neurotrophic factor (BDNF) and its receptor, and PUFA profile in the hippocampus were analyzed.

Results

IL-1β elevated biomarkers of microglial CD11b and astrocyte GFAP expression, increased the expression of APP, tumor-necrosis factor (TNF)-α, but reduced BDNF and its receptor (TrKB). IL-1β also lowered n-3 EPA and docosapentaenoic acid concentrations but increased n-6 PUFAs and cPLA2 activity in the hippocampus. EPA supplement normalized the n-3 and n-6 PUFA profiles and cPLA2 levels, inhibited glial activation, reduced APP and TNF-α expression, as well as up-regulated BDNF and TrKB.

Conclusion

Supplementation with EPA appear to have potential effects on improving glial over-activation, n3/n6 imbalance and BDNF down-regulation, which contribute to anti-inflammatory and may provide beneficial effects on inflammation-associated disease such as AD.

     

Dietary fatty acid intake and prostate cancer survival in Örebro County, Sweden

Although dietary fat has been associated with prostate cancer risk, the association between specific fatty acids and prostate cancer survival remains unclear. Dietary intake of 14 fatty acids was analyzed in a population-based cohort of 525 Swedish men with prostate cancer in ?rebro County (1989-1994). Multivariable hazard ratios and 95% confidence intervals for time to prostate cancer death by quartile and per standard deviation increase in intake were estimated by Cox proportional hazards regression. Additional models examined the association by stage at diagnosis (localized: T0-T2/M0; advanced: T0-T4/M1, T3-T4/M0). Among all men, those with the highest omega-3 docosahexaenoic acid and total marine fatty acid intakes were 40% less likely to die from prostate cancer (P(trend) = 0.05 and 0.04, respectively). Among men with localized prostate cancer, hazard ratios of 2.07 (95% confidence interval: 0.93, 4.59; P(trend) = 0.03) for elevated total fat, 2.39 (95% confidence interval: 1.06, 5.38) for saturated myristic acid, and 2.88 (95% confidence interval: 1.24, 6.67) for shorter chain (C4-C10) fatty acid intakes demonstrated increased risk for disease-specific mortality for the highest quartile compared with the lowest quartile. This study suggests that high intake of total fat and certain saturated fatty acids may worsen prostate cancer survival, particularly among men with localized disease. In contrast, high marine omega-3 fatty acid intake may improve disease-specific survival for all men.