Journal of Nutrition Nutrition and Disease

Increased Tissue Arachidonic Acid and Reduced Linoleic Acid in a Mouse Model of Cystic Fibrosis Are Reversed by Supplemental Glycerophospholipids Enriched in Docosahexaenoic Acid [Nutrition and Disease]

Fri, 20 Nov 2009 10:01:59 PST

An imbalance in (n-6)/(n-3) PUFA has been reported in cystic fibrosis (CF) patients. Glycerophospholipids enriched in docosahexaenoic acid (GPL-DHA) have been shown to regulate the (n-6)/(n-3) fatty acid ratio in the elderly. Here, we tested the effect of GPL-DHA supplementation on PUFA status in F508del homozygous CF mice. GPL-DHA liposomes were administrated by gavage (60 mg DHA/kg daily, i.e. at maximum 1.4 mg DHA/d) to 1.5-mo-old CF mice (CF+DHA) and their corresponding wild-type (WT) homozygous littermates (WT+DHA) for 6 wk. The PUFA status of different tissues was determined by GC and compared with control groups (CF and WT). There was an alteration in the (n-6) PUFA pathway in several CF-target organs in CF compared with WT mice, as evidenced by a higher level of arachidonic acid (AA) in membrane phospholipids or whole tissue (21 and 39% in duodenum-jejunum, 32 and 38% in ileum, and 19 and 43% in pancreas). Elevated AA levels were associated with lower linoleic acid (LA) and higher dihomo--linolenic acid levels. No DHA deficiency was observed. GPL-DHA treatment resulted in different PUFA composition changes depending on the tissue (increase in LA, decrease in elevated AA, DHA increase, increase in (n-6)/(n-3) fatty acid ratio). However, the DHA/AA ratio consistently increased in all tissues in CF+DHA and WT+DHA mice. Our study demonstrates the effectiveness of an original oral DHA formulation in counter-balancing the abnormal (n-6) fatty acid metabolism in organs of CF mice when administrated at a low dose and highlights the potential of the use of GPL-DHA as nutritherapy for CF patients.

A New Dietary Inflammatory Index Predicts Interval Changes in Serum High-Sensitivity C-Reactive Protein [Nutrition and Disease]

Fri, 20 Nov 2009 10:02:00 PST

Inflammation is associated with a number of chronic conditions, such as cancer and cardiovascular disease. Reducing inflammation may help prevent or treat these conditions. Diet has consistently been shown to modulate inflammation. To facilitate research into the inflammatory effect of diet on health in humans, we sought to develop and validate an Inflammatory Index designed to assess the inflammatory potential of individuals' diets. An Inflammatory Index was developed based on the results of an extensive literature search. Using data from a longitudinal observational study that carefully measured diet and the inflammatory marker, serum high-sensitivity (hs) C-reactive protein (CRP), in ~600 adults for 1 y, we conducted analyses to test the effect of Inflammatory Index score on hs-CRP as a continuous and dichotomous (≤3 mg/L, >3 mg/L) indicator of inflammatory response, while controlling for important potential confounders. Results based on continuous measures of hs-CRP suggested that an increasing Inflammatory Index score (representing movement toward an antiinflammatory diet) was associated with a decrease in hs-CRP. Analyses using hs-CRP as a dichotomous variable showed that an antiinflammatory diet was associated with a decrease in the odds of an elevated hs-CRP (P = 0.049). The results are consistent with the ability of the Inflammatory Index to predict hs-CRP and provide additional evidence that diet plays a role in the regulation of inflammation, even after careful control of a wide variety of potential confounders.

Oral Administration of 3,3'-Diindolylmethane Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells in BALB/c Mice [Nutrition and Disease]

Fri, 20 Nov 2009 10:02:00 PST

3,3'-diindolylmethane (DIM) is the major in vivo product of the acid-catalyzed oligomerization of indole-3-carbinol present in cruciferous vegetables, and it has been shown to exhibit anticancer properties. In this study, we assessed the effects of DIM on the metastasis of 4T1 mouse mammary carcinoma cells. In vitro culture studies showed that DIM dose-dependently inhibited the migration, invasion, and adhesion of 4T1 cells at concentrations of 0–10 µmol/L without attendant changes in cell viability. In an in vivo lung metastasis model, 4T1 cells (2 x 10⁵ cells/mouse) were injected into the tail veins of syngeneic female BALB/c mice. Beginning on the second day, the mice were subjected to gavage with 0–10 mg DIM/(kg body weight · d) for 13 d. Oral DIM administration resulted in a marked reduction in the number of pulmonary tumor nodules. DIM treatment significantly reduced the levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and vascular cell adhesion molecule (VCAM)-1 and increased TIMP-2 levels in the sera and lungs of mice injected with 4T1 cells. Additionally, DIM treatment reduced the serum concentrations of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF). We have demonstrated that DIM profoundly inhibits the lung metastasis of 4T1 cells, which was accompanied by reduced levels of MMP, adhesion molecules, and proinflammatory cytokines. These results indicate that DIM has potential as an antimetastatic agent for the treatment of breast cancer.

Dietary Fish Oil Exerts Hypolipidemic Effects in Lean and Insulin Sensitizing Effects in Obese LDLR-/- Mice [Nutrition and Disease]

Saraswathi, V., Morrow, J. D., Hasty, A. H. — Fri, 20 Nov 2009 10:02:00 PST

Obesity is often associated with dyslipidemia, insulin resistance, and hypertension. Together, these metabolic perturbations greatly increase the risk of developing cardiovascular disease and diabetes. Although fish oil is a well-established hypolipidemic agent, the mechanisms by which it mediates its lipid-lowering effects are not clear. In addition, it has not been established whether dietary fish oil has different effects in lean and obese mice. LDL receptor deficient (LDLR–/–) and leptin deficient mice on a LDLR–/– background (ob/ob;LDLR–/–) were fed a high fat diet (39% total fat) supplemented with 6% olive oil or fish oil for 6 wk. Fish oil supplementation resulted in lower concentrations of plasma total cholesterol (P < 0.01), triglycerides (P < 0.01), and free fatty acids (P < 0.001) in lean LDLR–/– mice, but not in ob/ob;LDLR–/– mice. In contrast, a fish oil diet did not modulate insulin sensitivity in lean LDLR–/– mice, but it improved insulin sensitivity in ob/ob;LDLR–/– mice (P < 0.05) compared with olive oil fed ob/ob;LDLR–/– mice. Interestingly, plasma adiponectin concentrations were significantly higher and hepatic steatosis was reduced in both mouse models upon fish oil feeding. Finally, fish oil fed LDLR–/– mice exhibited higher hepatic AMP activated protein kinase (AMPK) phosphorylation (P < 0.05), whereas AMPK phosphorylation was not elevated by fish oil feeding in ob/ob;LDLR–/– mice. Taken together, our data suggest that fish oil reduces hepatic steatosis in both lean and obese mice, has potent plasma lipid lowering effects in lean mice, and exerts insulin sensitizing effects in obese mice.

Products of the Colonic Microbiota Mediate the Effects of Diet on Colon Cancer Risk [Nutrition and Disease]

Tue, 20 Oct 2009 10:01:50 PDT

It is estimated that most colon cancers can be attributed to dietary causes. We have hypothesized that diet influences the health of the colonic mucosa through interaction with the microbiota and that it is the milieu interior that regulates mucosal proliferation and therefore cancer risk. To validate this further, we compared colonic contents from healthy 50- to 65-y-old people from populations with high and low risk, specifically low risk Native Africans (cancer incidence <1:100,000; n = 17), high risk African Americans (risk 65:100,000; n = 17), and Caucasian Americans (risk 50:100,000; n = 18). Americans typically consume a high-animal protein and -fat diet, whereas Africans consume a staple diet of maize meal, rich in resistant starch and low in animal products. Following overnight fasting, rapid colonic evacuation was performed with 2 L polyethylene glycol. Total colonic evacuants were analyzed for SCFA, vitamins, nitrogen, and minerals. Total SCFA and butyrate were significantly higher in Native Africans than in both American groups. Colonic folate and biotin content, measured by Lactobacillus rhamnoses and Lactobacillus plantarum ATCC 8014 bioassay, respectively, exceeded normal daily dietary intakes. Compared with Africans, calcium and iron contents were significantly higher in Caucasian Americans and zinc content was significantly higher in African Americans, but nitrogen content did not differ among the 3 groups. In conclusion, the results support our hypothesis that the microbiota mediates the effect diet has on colon cancer risk by their generation of butyrate, folate, and biotin, molecules known to play a key role in the regulation of epithelial proliferation.

Trans-11 Vaccenic Acid Reduces Hepatic Lipogenesis and Chylomicron Secretion in JCR:LA-cp Rats [Nutrition and Disease]

Tue, 20 Oct 2009 10:01:51 PDT

Trans-11 vaccenic acid (VA) is the predominant trans isomer in ruminant fat and a major precursor to the endogenous synthesis of cis9,trans11-conjugated linoleic acid in humans and animals. We have previously shown that 3-wk VA supplementation has a triglyceride (TG)-lowering effect in a rat model of dyslipidemia, obesity, and metabolic syndrome (JCR:LA-cp rats). The objective of this study was to assess the chronic effect (16 wk) of VA on lipid homeostasis in both the liver and intestine in obese JCR:LA-cp rats. Plasma TG (P < 0.001), total cholesterol (P < 0.001), LDL cholesterol (P < 0.01), and nonesterified fatty acid concentrations, as well as the serum haptoglobin concentration, were all lower in obese rats fed the VA diet compared with obese controls (P < 0.05). In addition, there was a decrease in the postprandial plasma apolipoprotein (apo)B48 area under the curve (P < 0.05) for VA-treated obese rats compared with obese controls. The hepatic TG concentration and the relative abundance of fatty acid synthase and acetyl-CoA carboxylase proteins were all lower (P < 0.05) in the VA-treated group compared with obese controls. Following acute gastrointestinal infusion of a VA-triolein emulsion in obese rats that had been fed the control diet for 3 wk, the TG concentration was reduced by 40% (P < 0.05) and the number of chylomicron (CM) particles (apoB48) in nascent mesenteric lymph was reduced by 30% (P < 0.01) relative to rats infused with a triolein emulsion alone. In conclusion, chronic VA supplementation significantly improved dyslipidemia in both the food-deprived and postprandial state in JCR:LA-cp rats. The appreciable hypolipidemic benefits of VA may be attributed to a reduction in both intestinal CM and hepatic de novo lipogenesis pathways.

1,2-Vinyldithiin from Garlic Inhibits Differentiation and Inflammation of Human Preadipocytes [Nutrition and Disease]

Keophiphath, M., Priem, F., Jacquemond-Collet, I., Clement, K., Lacasa, D. — Tue, 20 Oct 2009 10:01:51 PDT

Obesity is a state of chronic low-grade inflammation. Limiting white adipose tissue (WAT) expansion and therefore reducing inflammation could be effective in preventing the progression of obesity and the development of associated complications. We investigated the effects of 1,2-vinyldithiin (1,2-DT), a garlic-derived organosulfur, on the differentiation and inflammatory state of human preadipocytes. Preadipocytes were prepared from subcutaneous adipose tissue of nonobese young women and differentiated in the presence of 1,2-DT. Inflammatory preadipocytes were obtained following treatment with human macrophage-secreted factors. 1,2-DT (100 µmol/L) significantly reduced gene expression of PPAR2 (–40%), CCAAT/enhancer binding protein- (–25%), lipoprotein lipase (–22%), leptin (–30%), and adiponectin (–15%). Lipid accumulation was also significantly diminished in preadipocytes differentiated in the presence of 100 µmol/L 1,2-DT (–37%) compared with controls. Furthermore, 100 µmol/L 1,2-DT treatment for 10 d significantly reduced PPAR activity (–27%). The protein expression of perilipin and the secretion levels for 2 adipokines, leptin and adiponectin, were significantly diminished in 1,2-DT-cultured preadipocytes (–37, –51, and –43%, respectively). Moreover, the secretion of inflammatory molecules (interleukin-6 and monocyte chemoattractant protein-1) induced by macrophage-secreted factors was partially abolished in 100 µmol/L 1,2-DT–treated preadipocytes (–28 and –25%, respectively). In conclusion, we demonstrated that 1,2-DT, a garlic-derived organosulfur, has antiadipogenic and antiinflammatory actions on human preadipocytes and may be a novel, antiobesity nutraceutical.

Flaxseed and Pure Secoisolariciresinol Diglucoside, but Not Flaxseed Hull, Reduce Human Breast Tumor Growth (MCF-7) in Athymic Mice [Nutrition and Disease]

Chen, J., Saggar, J. K., Corey, P., Thompson, L. U. — Tue, 20 Oct 2009 10:01:51 PDT

Previous studies have shown that dietary flaxseed (FS) can reduce the growth of established human breast tumors in athymic mice with low circulating estrogen concentrations. In this study, we determined the effect of FS compared with pure lignan at the level it is present in FS [secoisolariciresinol diglucoside (SDG)] and to the lignan-rich fraction [FS hull (FH)] on human breast tumor growth and their potential mechanisms of action. Ovariectomized, athymic mice, each with an implanted 17 β-estradiol (E2) pellet (0.36 mg), were injected with human estrogen receptor (ER) positive breast cancer cells (MCF-7). When tumors were established, the E2 pellet was removed. Mice were fed either the control basal diet (BD), FS (100 g/kg diet), SDG (1 g/kg diet), or FH (18 g/kg diet) for 8 wk. Compared with the BD, FS and SDG significantly decreased the palpable tumor size, but effects of FS, SDG, and FH did not differ from one another. All treatments significantly inhibited cell proliferation, but only FS and SDG induced significantly higher apoptosis. Both FS and SDG significantly decreased mRNA expressions of Bcl2, cyclin D1, pS2, ER, and ERβ, epidermal growth factor receptor, and insulin-like growth factor receptor. FS also reduced human epidermal growth factor receptor 2 mRNA and SDG decreased phospho-specific mitogen-activated protein kinase expression. FH did not significantly reduce these biomarkers. In conclusion, pure SDG has a similar effect as FS in reducing tumor growth and in mechanisms of action, including downregulating ER- and growth factor-mediated cell signaling. The lesser effects of FH indicate a need for a higher dose to be more effective.

Rats Fed Fructose-Enriched Diets Have Characteristics of Nonalcoholic Hepatic Steatosis [Nutrition and Disease]

Tue, 20 Oct 2009 10:01:51 PDT

Nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease are increasing in adults and are likely to be increasing in children. Both conditions are hepatic manifestations of metabolic syndrome. Experimental animals fed fructose-enriched diets are widely recognized as good models for metabolic syndrome. However, few reports have described the hepatic pathology of these experimental animals. In this study, 5-wk-old Wistar specific pathogen-free rats, which are a normal strain, were fed experimental diets for 5 wk. We then evaluated the degree of steatohepatitis. The 5 diet groups were as follows: cornstarch (70% wt:wt) [control (C)], high-fructose (70%) (HFr), high-sucrose (70%) (HS), high-fat (15%) (HF), and high-fat (15%) high-fructose (50%) (HFHFr) diets. The macrovesicular steatosis grade, liver:body weight ratio, and hepatic triglyceride concentration were significantly higher in the HFr group than in the other 4 groups. However, the HFr group had a significantly lower ratio of epididymal white fat:body weight than the other 4 groups and had a lower final body weight than the HF and HFHFr groups. The HF group had a greater final body weight than the C, HFr, and HS groups, but no macrovesicular steatosis was observed. The HFr group had a significantly higher grade of lobular inflammation than the other 4 groups. The distribution of lobular inflammation was predominant over portal inflammation, which is consistent with human NASH. In conclusion, rats fed fructose-enriched diets are a better model for NASH than rats fed fat-enriched diets.

Western-Style Diets Induce Oxidative Stress and Dysregulate Immune Responses in the Colon in a Mouse Model of Sporadic Colon Cancer [Nutrition and Disease]

Tue, 20 Oct 2009 10:01:51 PDT

A Western-style diet (WD), defined by high-fat, low-calcium, and vitamin D content, is associated with increased risk of human colorectal cancer. Understanding molecular mechanisms altered by the WD is crucial to develop preventive and therapeutic strategies. Effects of a WD on the colonic transcriptome of C57Bl/6J mice, a model for sporadic colon cancer, were studied at endpoints before tumors occur. To assess whether a WD induces inflammatory changes, expression profiles of a broad spectrum of inflammatory proteins were performed and numbers of lamina propria macrophages were determined with semiquantitative morphometry. Transcriptome changes were translated into molecular interaction network maps and pathways. Pathways related to oxidative stress response; lipid, glutathione, and xenobiotic metabolism; and the immune response were perturbed by the WD. Several nuclear factor-erythroid 2-related factor 2- and aryl hydrocarbon receptor-dependent genes, including those coding for enzymes involved in phase 1 and 2 drug metabolism and oxidative stress responses, were induced. Oxidative stress was demonstrated by measurements of endogenous colonic redox-sensitive compound concentrations. Perturbations in immune response-related pathways, expression of inflammatory proteins, and increased numbers of lamina propria macrophages showed that the WD significantly alters the local colonic immune response. Collectively, these data suggest that consumption of a WD interferes with networks of related biological response pathways involving colonic lipid metabolism, oxidative stress, and the immune response. These new findings impact our understanding of links between consumption of WD and colon carcinogenesis, providing additional information for developing preventive means for decreasing colorectal cancer risk.

Olive Leaf Extract and Its Main Component Oleuropein Prevent Chronic Ultraviolet B Radiation-Induced Skin Damage and Carcinogenesis in Hairless Mice [Nutrition and Disease]

Kimura, Y., Sumiyoshi, M. — Tue, 20 Oct 2009 10:01:51 PDT

Chronic exposure to solar UV radiation damages skin, increasing its thickness and reducing its elasticity, and causes skin cancer. Our aim in this study was to examine the effects of an olive leaf extract and its component oleuropein on skin damage and the incidence of skin tumors caused by long-term UVB irradiation in hairless mice. Male hairless mice (5 wk old) were divided into 6 groups, including a non-UVB group, a vehicle-treated UVB group (control), 2 olive leaf extract-treated UVB groups, and 2 oleuropein-treated UVB groups. Five groups were UVB irradiated (36–180 mJ/cm²) 3 times each week for 30 wk and skin thickness and elasticity after UVB irradiation were measured every week. Olive leaf extract (300 and 1000 mg/kg) and oleuropein (10 and 25 mg/kg) were administered orally twice daily every day for 30 wk. The extract and oleuropein significantly inhibited increases in skin thickness and reductions in skin elasticity, and skin carcinogenesis and tumor growth. Furthermore, they prevented increases in the expression of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13 as well as in levels of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in the skin. Based on histological evaluation, they prevented increases in the expression of Ki-67 and CD31-positive cells induced by the irradiation. These results suggest that the preventative effects of the olive leaf extract and oleuropein on chronic UVB-induced skin damage and carcinogenesis and tumor growth may be due to inhibition of the expression of VEGF, MMP-2, MMP-9, and MMP-13 through a reduction in COX-2 levels.

Flaxseed Oil Supplementation Increases Plasma F1-Phytoprostanes in Healthy Men [Nutrition and Disease]

Barden, A. E., Croft, K. D., Durand, T., Guy, A., Mueller, M. J., Mori, T. A. — Fri, 18 Sep 2009 10:01:30 PDT

Supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been reported to reduce lipid peroxidation products formed from arachidonic acid (F₂-isoprostanes) in healthy humans, as well as in those under oxidative stress. -Linolenic acid (ALA) is a precursor to EPA and DHA; however, its conversion in humans is thought to be inefficient. ALA can also undergo free radical oxidation, forming compounds known as F₁-phytoprostanes, which are found in all plants and are in high concentrations in plant pollens. In this study, we examined the effect of ALA supplementation on plasma and urine F₁-phytoprostane and F₂-isoprostane concentrations in men. Thirty-six nonsmoking men, aged 20–65 y, were recruited from the general population and randomly allocated to consume 9 g/d of either flaxseed oil (62% ALA, 5.4 g/d) or olive oil (placebo) for 4 wk in a parallel design. At baseline and after 4 wk of supplementation, blood samples and a 24-h urine sample were collected for measurement of plasma and urinary F₁-phytoprostanes and F₂-isoprostanes and plasma fatty acids. Compared with the olive oil group, plasma phospholipid ALA was greater (P < 0.0001), as were F₁-phytoprostanes in plasma (P = 0.049) and urine (P = 0.06) in the flaxseed oil group after 4 wk supplementation. Flaxseed oil did not affect plasma or urinary F₂-isoprostanes. The greater plasma F₁-phytoprostane concentration in the flaxseed oil group most likely resulted from the increased plasma concentration of the ALA substrate and/or the F₁-phytoprostane content of the flaxseed oil. Future studies are needed to determine the physiological importance of increased plasma and urine F₁-phytoprostanes and their relevance to heart disease prevention.

Tart Cherry Juice Decreases Oxidative Stress in Healthy Older Men and Women [Nutrition and Disease]

Fri, 18 Sep 2009 10:01:30 PDT

Compared with young adults, older adults have significantly impaired capacities to resist oxidative damage when faced with acute stress such as ischemia/reperfusion. This impairment likely contributes to increased morbidity and mortality in older adults in response to acute trauma, infections, and the susceptibility to diseases such as atherosclerosis, cancer, diabetes, and Alzheimer's disease. Consumption of foods high in polyphenols, particularly anthocyanins, have been associated with improved health, but the mechanisms contributing to these salutary effects remain to be fully established. This study tested the hypothesis that consumption of tart cherry juice containing high levels of anthocyanins improves the capacity of older adults to resist oxidative damage during acute oxidative stress. In a double-blind, placebo-controlled, crossover design, 12 volunteers [6 men and 6 women; age 69 ± 4 y (61–75 y)] consumed in random order either tart cherry juice or placebo (240 mL twice daily for 14 d) separated by a 4-wk washout period. The capacity to resist oxidative damage was measured as the changes in plasma F₂-isoprostane levels in response to forearm ischemia-reperfusion (I/R) before and after each treatment. The tart cherry juice intervention reduced the I/R-induced F₂-isoprostane response (P < 0.05), whereas placebo had no significant effect. The tart cherry juice intervention also reduced basal urinary excretion of oxidized nucleic acids (8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine) (P < 0.05) but not urinary excretion of isoprostanes. These data suggest that consumption of tart cherry juice improves antioxidant defenses in vivo in older adults as shown by an increased capacity to constrain an oxidative challenge and reduced oxidative damage to nucleic acids.

Liver Carbohydrate and Lipid Metabolism of Insulin-Deficient Mice Is Altered by trans-10, cis-12 Conjugated Linoleic Acid [Nutrition and Disease]

Jourdan, T., Djaouti, L., Demizieux, L., Gresti, J., Verges, B., Degrace, P. — Fri, 18 Sep 2009 10:01:30 PDT

Feeding mice the trans-10, cis-12 (t10c12) conjugated linoleic acid (CLA) isomer is associated with lipodystrophy, insulin resistance, hyperinsulinemia, and liver steatosis. It has been hypothesized that CLA-induced liver steatosis is the result of increased hepatic lipogenesis stimulated by high insulin levels. We studied the effects of a 12-d t10c12CLA treatment (1 g/100 g diet) on liver carbohydrate and lipid metabolism in control and streptozotocin (STZ)-injected mice. STZ mice were characterized by insulin deficiency, hypertriglyceridemia, and depletion of liver triglyceride and glycogen. Remarkably, feeding t10c12CLA to diabetic mice (STZ-CLA) normalized these variables. Reconstitution of fat stores in the livers of STZ-CLA mice was associated with lower fatty acid (FA) oxidation rates and greater malonyl-CoA concentration than in STZ mice. FA translocase and VLDL receptor mRNA levels were greater in STZ-CLA than in STZ mice, suggesting that t10c12CLA increased liver lipid uptake. Phosphoenolpyruvate carboxykinase mRNA levels and AMP kinase phosphorylation were lower in STZ-CLA than in STZ mice, indicating that t10c12CLA may reduce glucogenic activity and promote glycogenesis in diabetic mice. Because glycemia and glucokinase expression were not modified by t10c12CLA treatment, we postulated that glycogen accumulation is likely not the result of an effect of t10c12CLA on plasma glucose utilization, but rather is due to the contribution of lactate, the concentration of which was higher in muscle of STZ-CLA mice. The results demonstrate that t10c12CLA stimulates liver lipid accumulation in the absence of insulin and, thus, suggest that t10c12CLA can improve liver carbohydrate and lipid metabolism in type I diabetic mice.

Supplemental Dietary Racemic Equol Has Modest Benefits to Bone but Has Mild Uterotropic Activity in Ovariectomized Rats [Nutrition and Disease]

Fri, 18 Sep 2009 10:01:30 PDT

Soy isoflavones and their metabolites, with estrogenic activity, have been considered candidates for reducing postmenopausal bone loss. In this study, we examined the effect of dietary equol, a bioactive metabolite of the soy isoflavone daidzein, on equol tissue distribution, bone parameters, and reproductive tissue activity using an adult ovariectomized (OVX) rat model. An 8-wk feeding study was conducted to compare 4 dietary treatments of equol (0, 50, 100, 200 mg/kg diet) in 6-mo-old OVX female Sprague-Dawley rats. A dose response increase in tissue equol concentrations was observed for serum, liver, kidney, and heart, and a plateau occurred at 100 mg equol/kg diet for intestine. In OVX rats receiving 200 mg equol/kg diet, femoral calcium concentration was greater than those receiving lower doses but was still less than SHAM (P < 0.05), and other bone measures were not improved. Tibia calcium concentrations were lower in OVX rats receiving 100 and 200 mg equol/kg diet compared with the OVX control rats. Trabecular bone mineral density of tibia was also lower in equol-fed OVX rats. At this dietary equol intake, uterine weight was higher (P < 0.05) than in other OVX groups but lower than the SHAM-operated intact rats. The 200 mg/kg diet dose of dietary equol significantly increased proliferative index in the uterine epithelium. Dietary equol had no stimulatory effect on mammary gland epithelium. We conclude that in OVX rats, a dietary equol dose that had modest effect on bone also exerts mild uterotropic effects.

Consumption of Green Tea Extract Results in Osteopenia in Growing Male Mice [Nutrition and Disease]

Fri, 18 Sep 2009 10:01:30 PDT

Consumption of green tea may reduce body weight gain. Although many disorders are related to obesity, bone mass is positively correlated with body mass. Therefore, our purpose in this study was to determine the effects of green tea extract (GTE) on bone mass and architecture in rapidly growing lean [C57BL/6 wild type (WT)] and genetically obese, leptin-deficient (ob/ob) male mice. Five-week-old lean and ob/ob mice were assigned to diets containing GTE at 0, 1, or 2% for 6 wk. Femoral and lumbar vertebral bone volume and architecture were evaluated by micro-computed tomography (µCT). Following µCT analysis, femora were ashed to determine bone mineral content and density. Compared with WT mice, ob/ob mice had shorter femora (P < 0.001), lower femoral bone volume (P < 0.001), and lower femoral bone mineral content (P < 0.001), but higher cancellous bone volume in lumbar vertebrae (P < 001). Neither genotype nor treatment affected femoral bone mineral density, indicating normal mineralization. GTE consumption resulted in lower femur length, volume, mineral content, cortical volume, and cortical thickness (P < 0.001), as well as lower cancellous bone volume/tissue volume (P < 0.008) and trabecular thickness (P < 0.004) in lumbar vertebrae. The results indicate that leptin is not essential for the reduced gains in body weight and bone mass due to GTE in growing mice and suggest that consumption of large quantities of green tea may reduce the rate of bone accumulation during growth.

Women's Health Initiative Diet Intervention Did Not Increase Macular Pigment Optical Density in an Ancillary Study of a Subsample of the Women's Health Initiative [Nutrition and Disease]

Thu, 20 Aug 2009 10:02:30 PDT

In this study, we examined the impact of long-term (>8 y), low-fat, high-fruit and -vegetable diets on levels of lutein and zeaxanthin in the macula of the retina, as indicated by the OD of macular pigment. Macular pigment OD, measured by heterochromatic flicker photometry, was compared in women aged 60–87 y, who, 7–18 mo earlier (median 12 mo), had been in the dietary modification intervention (n = 158) or comparison (n = 236) groups of the Women's Health Initiative (WHI) at the Madison, WI site for a mean of 8.5 y. Women in the intervention group ate more fruits and vegetables (mean ± SEM) (6.1 ± 0.2 vs. 4.6 ± 0.2 servings/d; P < 0.0001) and had higher intakes of lutein and zeaxanthin from foods and supplements (2.7 ± 0.2 vs. 2.1 ± 0.1 mg/d; P = 0.0003) than the comparison group. However, macular pigment density did not differ between the intervention (0.36 ± 0.02 OD units) and comparison (0.35 ± 0.01 OD units) groups. It tended to be higher (11%; P = 0.11) in women consuming lutein and zeaxanthin in the highest compared with the lowest quintile (median 6.4 vs. 1.1 mg/d). The increase in fruit and vegetable intake among dietary modification participants of this WHI subsample was not of sufficient magnitude to alter the mean density of retinal carotenoids, given other existing dietary conditions in this sample.

Soy Protein Reduces Serum LDL Cholesterol and the LDL Cholesterol:HDL Cholesterol and Apolipoprotein B:Apolipoprotein A-I Ratios in Adults with Type 2 Diabetes [Nutrition and Disease]

Thu, 20 Aug 2009 10:02:30 PDT

Type 2 diabetes is highly prevalent in North America and is associated with increased risk of cardiovascular disease (CVD). Evidence supports a role for soy protein in the reduction of serum lipids related to CVD risk; however, few studies have focused on adults with type 2 diabetes who are not on lipid-lowering medications and/or do not have diabetic complications. The purpose of this study was to determine the effect of soy protein isolate (SPI) consumption on serum lipids in adults with diet-controlled type 2 diabetes. Using a double-blind, randomized, crossover, placebo-controlled intervention study design, adults with diet-controlled type 2 diabetes (n = 29) consumed SPI (80 mg/d aglycone isoflavones) or milk protein isolate (MPI) for 57 d each separated by a 28-d washout period. Twenty-four–hour urine samples were collected on d 54–56 of each treatment for analysis of isoflavones and blood was collected on d 1 and 57 of each treatment and analyzed for serum lipids and apolipoproteins. SPI consumption increased urinary isoflavones compared with MPI. SPI consumption reduced serum LDL cholesterol (P = 0.04), LDL cholesterol:HDL cholesterol (P = 0.02), and apolipoprotein B:apolipoprotein A-I (P = 0.05) compared with MPI. SPI did not affect serum total cholesterol, HDL cholesterol, triacylglycerol, apolipoprotein B, or apolipoprotein A-I. These data demonstrate that consumption of soy protein can modulate some serum lipids in a direction beneficial for CVD risk in adults with type 2 diabetes.

Dietary Protein Digestion and Absorption Rates and the Subsequent Postprandial Muscle Protein Synthetic Response Do Not Differ between Young and Elderly Men [Nutrition and Disease]

Thu, 20 Aug 2009 10:02:30 PDT

Impaired digestion and/or absorption of dietary protein lowers postprandial plasma amino acid availability and, as such, could reduce the postprandial muscle protein synthetic response in the elderly. We aimed to compare in vivo dietary protein digestion and absorption and the subsequent postprandial muscle protein synthetic response between young and elderly men. Ten elderly (64 ± 1 y) and 10 young (23 ± 1 y) healthy males consumed a single bolus of 35 g specifically produced, intrinsically l-[1-¹³C]phenylalanine-labeled micellar casein (CAS) protein. Furthermore, primed continuous infusions with l-[ring-²H₅]phenylalanine, l-[1-¹³C]leucine, and l-[ring-²H₂]tyrosine were applied and blood and muscle tissue samples were collected to assess the appearance rate of dietary protein-derived phenylalanine in the circulation and the subsequent muscle protein fractional synthetic rate over a 6-h postprandial period. Protein ingestion resulted in a rapid increase in exogenous phenylalanine appearance in both the young and elderly men. Total exogenous phenylalanine appearance rates (expressed as area under the curve) were 39 ± 3 µmol·6 h·kg^–1 in the young men and 38 ± 2 µmol·6 h·kg^–1 in the elderly men (P = 0.73). In accordance, splanchnic amino acid extraction did not differ between young (72 ± 2%) and elderly (73 ± 1%) volunteers (P = 0.74). Muscle protein synthesis rates, calculated from the oral tracer, were 0.063 ± 0.006 and 0.054 ± 0.004%/h in the young and elderly men, respectively, and did not differ between groups (P = 0.27). We conclude that protein digestion and absorption kinetics and the subsequent muscle protein synthetic response following the ingestion of a large bolus of intact CAS are not substantially impaired in healthy, elderly men.

Epithelial Capacity for Apical Uptake of Short Chain Fatty Acids Is a Key Determinant for Intraruminal pH and the Susceptibility to Subacute Ruminal Acidosis in Sheep [Nutrition and Disease]

Penner, G. B., Aschenbach, J. R., Gabel, G., Rackwitz, R., Oba, M. — Thu, 20 Aug 2009 10:02:30 PDT

Subacute ruminal acidosis (SARA) is a common digestive disorder occurring in ruminants, with considerable variation in the severity of SARA observed among animals fed the same diet. Our aim in this study was to determine whether differences in the capacity of the ruminal epithelium for the apical uptake of acetate and butyrate (determined in Ussing chambers after slaughter) explains differences observed for the severity of a preceding episode of SARA in vivo. Adult sheep with an indwelling small ruminant ruminal pH measurement system (SRS) were randomly assigned to either a SARA induction treatment (oral drench containing 5 g glucose/kg body weight; n = 17) or a sham treatment (SHAM; n = 7; 12 mL water/kg body weight). Sheep receiving the glucose drench were further classified as nonresponders (NR; n = 7) or responders (RES; n = 7) according to their ruminal pH profile for the 3 h following the oral drench. Mean ruminal pH for the 3 h following the drench differed among groups (P < 0.001), with it being highest for SHAM (6.67 ± 0.08), intermediate for NR (5.97 ± 0.05), and lowest for RES (5.57 ± 0.08) sheep. The apical uptake of acetate and butyrate did not differ between SHAM and RES sheep. However, NR sheep had greater in vitro apical uptake of acetate and butyrate and a higher plasma β-hydroxybutyrate concentration than RES sheep, suggesting greater absorptive capacity for NR. Differences between NR and RES were attributed to greater bicarbonate-independent, nitrate-sensitive uptake of acetate (P = 0.007), a tendency for greater bicarbonate-dependent uptake of acetate (P = 0.071), and greater bicarbonate-independent uptake of butyrate (P = 0.022). These data indicate that differences in the rates and pathways for the uptake of acetate and butyrate explain a large proportion of the individual variation observed for the severity of SARA.