Consumption of Non-Nutritive Sweetener, Acesulfame Potassium Exacerbates Atherosclerosis through Dysregulation of Lipid Metabolism in ApoE-/- Mice.

Obesity is associated with the risk of cardiovascular disease, and non-nutritive sweetener, such as acesulfame potassium (AceK) has been used to combat obesity. However, the effects of AceK on cardiovascular disease are still unclear. In this study, high cholesterol diet (HCD)-fed ApoE-/- mice had dysregulated plasma lipid profile, and developed atherosclerosis, determined by atherosclerotic plaque in the aorta. Supplement of AceK in HCD worsened the dyslipidemia and increased atherosclerotic plaque, as compared with HCD-fed ApoE-/- mice. Since treatment of AceK in RAW264.7 macrophages showed no significant effects on inflammatory cytokine expressions, we then investigated the impacts of AceK on lipid metabolism. We found that AceK consumption enhanced hepatic lipogenesis and decreased ß-oxidation in ApoE-/- mice. In addition, AceK directly increased lipogenesis and decreased ß-oxidation in HepG2 cells. Taken together, a concurrent consumption of AceK exacerbated HCD-induced dyslipidemia and atherosclerotic lesion in ApoE-/- mice, and AceK might increase the risk of atherosclerosis under HCD.

Suppression of Lipid Accumulation by Indole-3-Carbinol Is Associated with Increased Expression of the Aryl Hydrocarbon Receptor and CYP1B1 Proteins in Adipocytes and with Decreased Adipocyte-Stimulated Endothelial Tube Formation.

This study investigated the effects of indole-3-carbinol (I3C) on adipogenesis- and angiogenesis-associated factors in mature adipocytes. The cross-talk between mature adipocytes and endothelial cells (ECs) was also explored by cultivating ECs in a conditioned medium (CM) by using I3C-treated adipocytes. The results revealed that I3C significantly inhibited triglyceride accumulation in mature adipocytes in association with significantly increased expression of AhR and CYP1B1 proteins as well as slightly decreased nuclear factor erythroid-derived factor 2-related factor 2, hormone-sensitive lipase, and glycerol-3-phosphate dehydrogenase expression by mature adipocytes. Furthermore, I3C inhibited CM-stimulated endothelial tube formation, which was accompanied by the modulated secretion of angiogenic factors in adipocytes, including vascular endothelial growth factor, interleukin-6, matrix metalloproteinases, and nitric oxide. In conclusion, I3C reduced lipid droplet accumulation in adipocytes and suppressed adipocyte-stimulated angiogenesis in ECs, suggesting that I3C is a potential therapeutic agent for treating obesity and obesity-associated disorders.

A diet containing grape powder ameliorates the cognitive decline in aged rats with a long-term high-fructose-high-fat dietary pattern.

Research has suggested that the consumption of foods rich in polyphenols is beneficial to the cognitive functions of the elderly. We investigated the effects of grape consumption on spatial learning, memory performance and neurodegeneration-related protein expression in aged rats fed a high-fructose-high-fat (HFHF) diet. Six-week-old Wistar rats were fed an HFHF diet to 66 weeks of age to establish a model of an HFHF dietary pattern, before receiving intervention diets containing different amounts of grape powder for another 12 weeks in the second part of the experiment. Spatial learning, memory performance and cortical and hippocampal protein expression levels were assessed. After consuming the HFHF diet for a year, results showed that the rats fed a high grape powder-containing diet had significantly better spatial learning and memory performance, lower expression of ß-amyloid and ß-secretase and higher expression of α-secretase than the rats fed a low grape powder-containing diet. Therefore, long-term consumption of an HFHF diet caused a decline in cognitive functions and increased the risk factors for neurodegeneration, which could subsequently be ameliorated by the consumption of a polyphenol-rich diet.

A high-cholesterol diet enriched with polyphenols from Oriental plums (Prunus salicina) improves cognitive function and lowers brain cholesterol levels and neurodegenerative-related protein expression in mice.

Ageing accompanied by a decline in cognitive performance may be a result of the long-term effects of oxidative stress on neurologic processes. It has been shown that high-cholesterol contents in the blood and brain may lead to the deposition of the ß-amyloid (Aß) protein in the brain, which damages brain cells. The present study was designed to observe the effect of polyphenol-rich Oriental plums on cognitive function and cerebral neurodegeneration-related protein expression in mice that were fed a high-cholesterol diet for 5 months. The study consisted of four groups: the control (Ctrl) group, which was fed the American Institute of Nutrition (AIN)-93M diet; the high cholesterol (HC) group, which was fed the AIN-93M diet with 5% cholesterol; the high cholesterol + low Oriental plum (LOP) group, which was fed the AIN-93M diet with 5% cholesterol and 2% Oriental plum powder; and the high cholesterol + high Oriental plum (HOP) group, which was fed the AIN-93M diet with 5% cholesterol and 5% Oriental plum powder. Measurements of cognitive function were assessed using the Morris water maze, and the mRNA expression of cholesterol hydroxylase (Cyp46), Aß and ß-secretase 1 (BACE1) were analysed. The results showed that cholesterol concentrations in both the blood and the brain were significantly higher in the HC group than in the Ctrl and HOP groups at the end of the trial. The high-cholesterol diet per se produced significant cognitive deficits, which were accompanied by a significantly increased mRNA expression of Cyp46, BACE1, Aß and 24-hydroxycholesterol in the brain cortex and hippocampus. However, all of these variables were non-significantly increased in the HOP group as compared to the Ctrl group. In conclusion, incorporating polyphenol-enriched Oriental plum into a high-cholesterol diet can ameliorate some of the symptoms of neurodegenerative conditions.

Soy Saponins Meditate the Progression of Colon Cancer in Rats by Inhibiting the Activity of ß -Glucuronidase and the Number of Aberrant Crypt Foci but Not Cyclooxygenase-2 Activity.

Objective. The effect of extracted crude soybean saponins on preneoplastic lesions, aberrant crypt foci (ACF), and the related mechanism were investigated. Research Methods and Procedures. Rats were assigned into five groups according to different doses of extracted crude soybean saponins and received 1,2-dimethylhydrazine (DMH) injection in week 5. In week 15, all rats were sacrificed. The number of ACFs, the cyclooxygenase-2 (COX-2) protein expression, the level of prostaglandins E2 (PGE2), and the activity of ß -glucuronidase were examined. Results. Results revealed that the consumption of extracted crude soybean saponins decreased the number of ACFs and the activity of ß -glucuronidase in rats, while the expression of COX-2 protein and PGE2 level were not affected. Conclusions. Soybean saponins were effective in inhibiting colon cancer by downregulating the activity of ß -glucuronidase in colonic mucosa but not the COX-2 protein expression and PGE2 level.

Antiobesity activities of indole-3-carbinol in high-fat-diet-induced obese mice.

OBJECTIVE: This study investigated the effects of indole-3-carbinol (I3C), a cruciferous vegetable derivative, on obesity and its associated factors in high-fat-diet-induced obese (DIO) mice. METHODS: Eighteen male C57BL/6 mice were randomly assigned to one of three groups: basal, high fat (HF), and HF + 5 mg/kg of I3C intraperitoneally (HFI). After 12 wk of treatment, obesity-associated factors, including body weight, organ weight, serum concentrations of glucose, triacylglycerol, insulin, and adipokines, and macrophage accumulation and lipid metabolism-associated factors in epididymal adipose tissue were measured. RESULTS: Body weight and epididymal adipose tissue weight were greater (P < 0.01), and adipocytes were larger in the HF group than in the basal and HFI groups. Compared with the HF group, the HFI group had improved glucose tolerance, a higher serum adiponectin concentration, lower serum glucose, triacylglycerol, insulin, and leptin concentrations, and less F4/80 expression in epididymal adipose tissue (P < 0.001). Furthermore, I3C treatment decreased acetyl coenzyme A carboxylase mRNA expression (P < 0.05) and increased peroxisome proliferator-activated receptor-γ protein expression (P < 0.05) in epididymal adipose tissue of DIO mice. CONCLUSION: The I3C treatment decreased body weight and fat accumulation and infiltrated macrophages in epididymal adipose tissue of DIO mice, and these reductions were associated with improved glucose tolerance and with modulated expression of adipokines and lipogenic-associated gene products, including acetyl coenzyme A carboxylase and peroxisome proliferator-activated receptor-γ.

Effects of consecutive high-dose alcohol administration on the utilization of sulfur-containing amino acids by rats.

In this study, we attempted to evaluate changes in sulfur-containing amino acid (SCAA) metabolism after short-term high-dose alcohol ingestion. At the beginning of the study, six animals were sacrificed as the baseline group and then other animals in the experiment were consecutively gavaged with alcohol (30%, 3 g/kg) for 7 days. Animals (n=6 each) were subsequently sacrificed at the time points of Days 1 (Group E1), 3 (Group E3) and 7 (Group E7). Blood samples and selected tissues were collected at each time interval. SCAA, pyridoxal phosphate (PLP) and glutathione (GSH) levels were analyzed. Results showed that taurine levels of tissues (brain, liver, heart and kidneys) all declined after the ethanol intervention and continued to decrease in selected tissues except the brain during the experiment. Furthermore, the trends of plasma taurine and PLP contents were highly correlated (r=.98, P=.045). A similar utilization pattern of plasma taurine and PLP indicated that transsulfuration preferred taurine production to GSH synthesis. The trend of plasma taurine levels being positively correlated with PLP levels reveals that dramatic transsulfuration occurred to meet the urgent demand for taurine by brain cells. In conclusion, we reported that continual alcohol ingestion alters SCAA utilization, especially by depletion of taurine and hypotaurine and by elevation of S-adenosyl homocysteine in the selected organs.

Suppression of inducible nitric oxide production by indole and isothiocyanate derivatives from Brassica plants in stimulated macrophages.

In this study, the effects of bioactive compounds derived from vegetables of the Brassica genus (Brassicaceae) including 2-phenylethyl isothiocyanate (PEITC), indole-3-carbinol (I3C), and indolo[3,2- b]carbazole (ICZ), on the inhibition of NO production in RAW 264.7 cells were explored. The results indicated that PEITC and I3C inhibited lipopolysaccharide (LPS)- and interferon-gamma (IFN-gamma)-induced NO production in RAW 264.7 cells, and this inhibition was in accordance with lowering the expression of iNOS protein and mRNA. On the contrary, ICZ, a derivative of I3C, had no significant effect on the stimulated NO production. In conclusion, the Brassica plants derivatives, PEITC and, to a lesser extent, I3C inhibit the LPS/IFN-gamma-induced NO production by lowering iNOS protein and mRNA expression in RAW 264.7 cells, in which the PEITC had a more potent inhibitory effect. Nevertheless, ICZ exhibits no inhibitory effect on the activated NO production (Indole-3-carbinol = indole-3-methanol).