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Biomedical subjects

J B German

Publications and source records attributed to J B German.

At least 19 recordsLinked to original sources

Unique phospholipid metabolism in mouse heart in response to dietary docosahexaenoic or alpha-linolenic acids.

Diet and fatty acid metabolism interact in yet unknown ways to modulate membrane fatty acid composition and certain cellular functions. For example, dietary precursors or metabolic products of n-3 fatty acid metabolism differ in their ability to modify specific membrane components. In the present study, the effect of dietary 22:6n-3 or its metabolic precursor, 18:3n-3, on the selective accumulation of 22:6n-3 by heart was investigated. The mass and fatty acid compositions of individual phospholipids (PL) in heart and liver were quantified in mice fed either 22:6n-3 (from crocodile oil) or 18:3n-3 (from soybean oil) for 13 wk. This study was conducted to determine if the selective accumulation of 22:6n-3 in heart was due to the incorporation of 22:6n-3 into cardiolipin (CL), a PL most prevalent in heart and known to accumulate 22:6n-3. Although heart was significantly enriched with 22:6n-3 relative to liver, the accumulation of 22:6n-3 by CL in heart could not quantitatively account for this difference. CL from heart did accumulate 22:6n-3, but only in mice fed preformed 22:6n-3. Diets rich in non-22:6n-3 fatty acids result in a fatty acid composition of phosphatidylcholine (PC) in heart that is unusually enriched with 22:6n-3. In this study, the mass of PC in heart was positively correlated with the enrichment of 22:6n-3 into PC. The increased mass of PC was coincident with a decrease in the mass of phosphatidylethanolamine, suggesting that 22:6n-3 induced PC synthesis by increasing phosphatidylethanolamine-N-methyltransferase activity in the heart.

Alligators and Crocodiles↗

Genomics: food and nutrition.

Nutrition is traditionally a multidisciplinary field applying principles of molecular biochemistry and statistical epidemiology to integrative metabolism and population health. Genomics, with its global perspective, is now reinventing the future of human metabolic health. Creative experimental designs are addressing metabolic questions in nutrition ranging from energy regulation to aging, and from mechanisms of absorption to the interspecies molecular crosstalk of bacteria and human cells within the intestine.

Animals↗

Interaction of estrogen and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with hepatic fatty acid synthesis and metabolism of male chickens (Gallus domesticus).

This study tested the hypothesis that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) antagonizes estrogen-induced hepatic lipid synthesis and metabolism in birds. Twenty immature male chickens (Gallus domesticus) were divided evenly into four groups: (1) vehicle control; (2) estrogen alone (1.0 mg/kg estradiol cypionate injected on three consecutive days); (3) TCDD alone (50 microg/kg injected on the fourth day); and (4) a combination of the estrogen and TCDD treatments. On day 14, liver samples were collected for quantitative fatty acid analysis by capillary gas chromatography. Birds treated with estrogen alone had increased total triacylglyceride concentrations with specific increases in the Delta9 desaturase products 16:1n7, 18:1n7, 18:1n9, and 20:1n9. In addition, estrogen treatment specifically increased 22:6n3 concentrations in both triacylglycerides and phospholipids. However, these increases in Delta9 desaturase products or 22:6n3 did not occur for birds treated with estrogen in combination with TCDD. TCDD and estrogen plus TCDD treatments increased phospholipid concentrations of the diet-derived polyunsaturated fatty acids 18:2n6, 18:3n6, 20:3n6, 18:3n3, and 20:5n3, although only the estrogen plus TCDD group had significantly increased total phospholipids. In cholesterol esters, all three treatments decreased concentrations of total fatty acids, saturated fatty acids, and Delta9 desaturase products compared to the control group.

Animals↗

Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells.

BACKGROUND: Polyphenolic phytochemicals inhibit vascular and inflammatory processes that contribute to disease. These effects are hypothesized to result from polyphenol-mediated alterations in cellular eicosanoid synthesis. OBJECTIVE: The objective was to determine and compare the ability of cocoa procyanidins to alter eicosanoid synthesis in human subjects and cultured human aortic endothelial cells. DESIGN: After an overnight fast, 10 healthy subjects (4 men and 6 women) consumed 37 g low-procyanidin (0.09 mg/g) and high-procyanidin (4.0 mg/g) chocolate; the treatments were separated by 1 wk. The investigation had a randomized, blinded, crossover design. Plasma samples were collected before treatment and 2 and 6 h after treatment. Eicosanoids were quantitated by enzyme immunoassay. Endothelial cells were treated in vitro with procyanidins to determine whether the effects of procyanidin in vivo were associated with procyanidin-induced alterations in endothelial cell eicosanoid synthesis. RESULTS: Relative to the effects of the low-procyanidin chocolate, high-procyanidin chocolate induced increases in plasma prostacyclin (32%; P<0.05) and decreases in plasma leukotrienes (29%; P<0.04). After the in vitro procyanidin treatments, aortic endothelial cells synthesized twice as much 6-keto-prostaglandin F(1alpha) (P<0.01) and 16% less leukotriene (P<0.05) as did control cells. The in vitro and in vivo effects of procyanidins on plasma leukotriene-prostacyclin ratios in culture medium were also comparable: decreases of 58% and 52%, respectively. CONCLUSION: Data from this short-term investigation support the concept that certain food-derived flavonoids can favorably alter eicosanoid synthesis in humans, providing a plausible hypothesis for a mechanism by which they can decrease platelet activation in humans.

Adult↗

Individual metabolism should guide agriculture toward foods for improved health and nutrition.

Genomics and bioinformatics have the vast potential to identify genes that cause disease by investigating whole-genome databases. Comparison of an individual's geno-type with a genomic database will allow the prescription of drugs to be tailored to an individual's genotype. This same bioinformatic approach, applied to the study of human metabolites, has the potential to identify and validate targets to improve personalized nutritional health and thus serve to define the added value for the next generation of foods and crops. Advances in high-throughput analytic chemistry and computing technologies make the creation of a vast database of metabolites possible for several subsets of metabolites, including lipids and organic acids. In creating integrative databases of metabolites for bioinformatic investigation, the current concept of measuring single biomarkers must be expanded to 3 dimensions to 1) include a highly comprehensive set of metabolite measurements (a profile) by multiparallel analyses, 2) measure the metabolic profile of individuals over time rather than simply in the fasted state, and 3) integrate these metabolic profiles with genomic, expression, and proteomic databases. Application of the knowledge of individual metabolism will revolutionize the ability of nutrition to deliver health benefits through food in the same way that knowledge of genomics will revolutionize individual treatment of dis-ease with pharmaceuticals.

Biomarkers↗

Fatty acid and triglyceride composition of milk fat from lactating Holstein cows in response to supplemental canola oil.

The objective was to determine the influence of dietary lipid on total and sn-2 fatty acid composition and triglyceride structure of milk fat in lactating Holstein cows. Five primiparous Holstein cows surgically fitted with ruminal and duodenal cannulas were used in a 4 x 5 incomplete Latin square. All cows received a basal diet. Treatments consisted of a basal diet with no supplemental canola oil (control), basal diet with canola oil added to the concentrate portion of the diet to provide 1.6% fat, basal diet with 330 g of canola oil infused directly into the rumen, and basal diet with 330 g of canola oil infused directly into the abomasum. Canola oil treatments decreased palmitic acid and increased oleic acid content of milk fat compared with the control. Stearate was higher when canola oil was rumen available compared with control and abomasal infusion. Abomasal infusion increased linoleic and linoleic acids in milk fat compared with the other treatments. The sn-2 fatty acid composition reflected total fatty acid composition. All canola oil treatments reduced palmitic acid and increased oleic acid content at the sn-2 position. Changes in sn-2 composition reflect specificity of the acyl transferases and substrate concentration. Triglyceride composition reported as carbon number was altered by canola oil. Triglycerides in carbon number C50, C52, and C54 were increased while C32, C34, and C36 were decreased.

Abomasum↗

Lactoferrin in infant formulas: effect on oxidation.

Lactoferrin is an iron transport protein present in human milk at an average concentration of 1.4 mg/mL. Commercially modified infant formulas based on cow's milk contain much lower amounts of lactoferrin (0.1 mg/mL lactoferrin) and soy based formulas have none. In addition to its role in iron transport, lactoferrin has bacteriostatic and bactericidal activities. Infant formulas are supplemented with relatively large amounts of iron (up to 12 mg/L). The effect of various concentrations of added lactoferrin and supplemental iron on lipid oxidation was tested in two different infant formulas. The extent of oxidation in the formulas as a function of time was determined by formation of hydroperoxides, production of hexanal, and fluorescence. On the basis of all three of these determinations, lactoferrin acted as an antioxidant in the absence and presence of different concentrations of supplemented iron. Lactoferrin inhibited oxidation in a concentration-dependent manner even at concentrations beyond its capacity to bind iron at its two high affinity binding sites. Lactoferrin can be used, therefore, as a dual purpose additive in infant formulas and similar food products for its antioxidant and its antimicrobial properties.

Humans↗

Activities of antioxidants are affected by colloidal properties of oil-in-water and water-in-oil emulsions and bulk oils.

The activity of alpha-tocopherol, Trolox, propyl gallate, gallic acid, methyl carnosoate, and carnosic acid was studied in two oil-in-water (o/w) emulsions, in two water-in-oil (w/o) emulsions, and in bulk oil with and without added emulsifiers. All antioxidants had either moderate or higher activity in bulk oil than in the emulsions. In most emulsions, the most polar antioxidants, propyl gallate and gallic acid, exhibited either prooxidant activity or no antioxidant activity. Methyl carnosoate was the most active antioxidant in w/o emulsions but was less active than Trolox in o/w emulsions. alpha-Tocopherol was less active in bulk oil than in emulsions, but its activity in bulk oil was markedly enhanced by the addition of o/w emulsifiers. Partitioning of antioxidants, hydrogen bonding, interphase transport, surface accessibility, and interaction of emulsifier with antioxidants are considered to be important parameters that determine antioxidant activity in lipid-containing systems.

Antioxidants↗

(+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine.

BACKGROUND: Red wine consumption may decrease the risk of coronary heart disease through the actions of its constituent flavonoids. (+)-Catechin is an abundant flavonoid in red wine. OBJECTIVE: The objective was to determine changes in plasma (+)-catechin concentrations after ingestion of a single, moderate serving of dealcoholized red wine reconstituted with either water (DRW) or water and alcohol (ARW). DESIGN: Nine subjects (5 men, 4 women) ingested, in random order, 120 mL DRW on one day and 120 mL ARW on another day. Both the DRW and ARW contained 35 mg (121 micromol) free (+)-catechin. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, and 8 h. Plasma was analyzed by gas chromatography-mass spectrometry for (+)-catechin after enzymatic release of sulfate and glucuronide conjugates. RESULTS: Calcium ions were needed to effectively hydrolyze (+)-catechin conjugates in plasma containing EDTA. Neither the ARW or DRW nor sex affected the area under the curve at 8 h, the maximum concentration (c(max)), or the time it took for plasma total (+)-catechin to reach maximum concentration (t(max)). Pooled mean (+/-SEM) values for the ARW and DRW were as follows: area under the curve, 306.1 +/- 29.5 nmol*h/L; c(max), 76.7 +/- 7.5 nmol/L; and t(max), 1.44 +/- 0.13 h. The half-life of (+)-catechin in plasma was significantly less (P = 0.038) after ingestion of the ARW (3.17 h) than after ingestion of the DRW (4.08 h). CONCLUSIONS: Increases in plasma total (+)-catechin concentrations were not significantly different after single moderate servings of either the ARW or DRW. Alcohol in the ARW hastened the elimination of (+)-catechin from the plasma compartment. (+)-Catechin elimination may represent excretion or conversion to methylated derivatives.

Adult↗

Chronic marginal iron intakes during early development in mice result in persistent changes in dopamine metabolism and myelin composition.

Marginal iron (Fe) deficiency is prevalent in children worldwide, yet the behavioral and biochemical effects of chronic marginal Fe intakes during early development are not well characterized. Using a murine model, previous work in our laboratory demonstrated persistent behavioral disturbances as a consequence of marginal Fe intakes during early development. In the present study, Swiss-Webster mice fed a control Fe diet (75 microgram Fe/g diet, n = 13 litters) or marginal Fe diet (14 microgram Fe/g diet, n = 16 litters) during gestation and through postnatal day (PND) 75 were killed on PND 75 for assessment of tissue mineral concentrations, dopamine metabolism, myelin fatty acid composition, and c- and m-aconitase activities. In addition, these outcomes were assessed in a group of offspring (n = 13 litters) fed a marginal Fe diet during gestation and lactation and then fed a control diet from PND 21-75. Marginal Fe mice demonstrated significant differences in brain iron concentrations, dopamine metabolism and myelin fatty acid composition relative to control mice; however, no difference in c- or m-aconitase activity was demonstrated in the brain. The postnatal consumption of Fe-adequate diets among marginal Fe offspring did not fully reverse all of the observed biochemical disturbances. This study demonstrates that chronic marginal Fe intakes during early development can result in significant changes in brain biochemistry. The persistence of some of these biochemical changes after postnatal Fe supplementation suggests that they are an irreversible consequence of developmental Fe restriction.

Aconitate Hydratase↗

The health benefits of wine.

Epidemiologic studies from numerous disparate populations reveal that individuals with the habit of daily moderate wine consumption enjoy significant reductions in all-cause and particularly cardiovascular mortality when compared with individuals who abstain or who drink alcohol to excess. Researchers are working to explain this observation in molecular and nutritional terms. Moderate ethanol intake from any type of beverage improves lipoprotein metabolism and lowers cardiovascular mortality risk. The question now is whether wine, particularly red wine with its abundant content of phenolic acids and polyphenols, confers additional health benefits. Discovering the nutritional properties of wine is a challenging task, which requires that the biological actions and bioavailability of the >200 individual phenolic compounds be documented and interpreted within the societal factors that stratify wine consumption and the myriad effects of alcohol alone. Further challenge arises because the health benefits of wine address the prevention of slowly developing diseases for which validated biomarkers are rare. Thus, although the benefits of the polyphenols from fruits and vegetables are increasingly accepted, consensus on wine is developing more slowly. Scientific research has demonstrated that the molecules present in grapes and in wine alter cellular metabolism and signaling, which is consistent mechanistically with reducing arterial disease. Future research must address specific mechanisms both of alcohol and of polyphenolic action and develop biomarkers of their role in disease prevention in individuals.

Alcohol Drinking↗

Food processing and lipid oxidation.

Food lipids are principally triacylglycerides, phospholipids and sterols found naturally in most biological materials consumed as food and added as functional ingredients in many processed foods. As nutrients, lipids, especially triglycerides, are a concentrated caloric source, provide essential fatty acids and are a solvent and absorption vehicle for fat-soluble vitamins and other nutrients. The presence of fat significantly enhances the organoleptic perception of foods, which partly explains the strong preference and market advantage of fat-rich foods. As a class, lipids contribute many desirable qualities to foods, including attributes of texture, structure, mouthfeel, flavor and color. However, lipids are also one of the most chemically unstable food components and will readily undergo free-radical chain reactions that not only deteriorate the lipids but also: (a) produce oxidative fragments, some of which are volatile and are perceived as the off-flavors of rancidity, (b) degrade proteins, vitamins and pigments and (c) cross-link lipids and other macromolecules into non-nutritive polymers. Free-radical chain reactions are thermodynamically favorable, and as a result, evolutionary selection has strongly influenced the chemistry, metabolism and structure of biological cells to prevent these reactions kinetically. However, the loss of native structure and the death of cells can dramatically accelerate the deteriorative reactions of lipid oxidation. The effects of all processing steps, including raw product selection, harvesting, storage, refining, manufacturing and distribution, on the quality of lipids in the final commodity are considerable. Certain key variables now known to influence oxidative processes can be targeted to increase food lipid stability during and after processing. Retention of or addition of exogenous antioxidants is a well-known consideration, but the presence and activity of catalysts, the integrity of tissues and cells, the quantity of polyunsaturated lipids and the structural properties of the final food product, including total surface area of lipids, and the nature of surfactant materials all play important roles in final product stability.

Antioxidants↗

Apple juice inhibits human low density lipoprotein oxidation.

Dietary phenolic compounds, ubiquitous in vegetables and fruits and their juices possess antioxidant activity that may have beneficial effects on human health. The phenolic composition of six commercial apple juices, and of the peel (RP), flesh (RF) and whole fresh Red Delicious apples (RW), was determined by high performance liquid chromatography (HPLC), and total phenols were determined by the Folin-Ciocalteau method. HPLC analysis identified and quantified several classes of phenolic compounds: cinnamates, anthocyanins, flavan-3-ols and flavonols. Phloridzin and hydroxy methyl furfural were also identified. The profile of phenolic compounds varied among the juices. The range of concentrations as a percentage of total phenolic concentration was: hydroxy methyl furfural, 4-30%; phloridzin, 22-36%; cinnamates, 25-36%; anthocyanins, n.d.; flavan-3-ols, 8-27%; flavonols, 2-10%. The phenolic profile of the Red Delicious apple extracts differed from those of the juices. The range of concentrations of phenolic classes in fresh apple extracts was: hydroxy methyl furfural, n.d.; phloridzin, 11-17%; cinnamates, 3-27%; anthocyanins, n.d.-42%; flavan-3-ols, 31-54%; flavonols, 1-10%. The ability of compounds in apple juices and extracts from fresh apple to protect LDL was assessed using an in vitro copper catalyzed human LDL oxidation system. The extent of LDL oxidation was determined as hexanal production using static headspace gas chromatography. The apple juices and extracts, tested at 5 microM gallic acid equivalents (GAE), all inhibited LDL oxidation. The inhibition by the juices ranged from 9 to 34%, and inhibition by RF, RW and RP was 21, 34 and 38%, respectively. Regression analyses revealed no significant correlation between antioxidant activity and either total phenolic concentration or any specific class of phenolics. Although the specific components in the apple juices and extracts that contributed to antioxidant activity have yet to be identified, this study found that both fresh apple and commercial apple juices inhibited copper-catalyzed LDL oxidation. The in vitro antioxidant activity of apples support the inclusion of this fruit and its juice in a healthy human diet.

Antioxidants↗

Butyric acid and tributyrin induce apoptosis in human hepatic tumour cells.

The anti-colon cancer effect of dietary fibre results in part from its fermentation into the short-chain fatty acid butyric acid (BA) by intestinal microflora. BA has potent anti-colon cancer properties owing to its ability to induce apoptosis in colon cancer cells. The colon is not the only location where BA may reach high concentrations, because dietary BA is rapidly absorbed and transported to the liver. We have investigated whether BA could induce apoptosis in transformed human liver (Hep G2) cells. Hep G2 cells treated with BA displayed acetylated histones, increased DNA fragmentation and morphological features consistent with apoptosis. These biochemical features of BA-treated liver cells are identical to those of BA-treated colon cells. In addition, we investigated whether BA present in tributyrin, a triacylglycerol more compatible for inclusion into colloidal lipid structures than BA, could also induce apoptosis in Hep G2 cells. Tributyrin induced DNA fragmentation and morphological features characteristic of apoptotic cells in Hep G2 cells. These results are a significant advance towards delivering BA via colloidal lipid particles to cancerous sites in vivo. This study showed that BA and tributyrin are potent apoptotic agents, and we suggest that sources of dietary BA, such as milk fat, may provide anti-liver cancer properties.

Acetylation↗

Effect of lactoferrin on oxidative stability of corn oil emulsions and liposomes.

Interest in using lactoferrin in foods for its antimicrobial activity inspired the present study of its antioxidant activity. Natural bovine lactoferrin inhibited oxidation in buffered corn oil emulsions and lecithin liposome systems at pH 6.6 and 50 degrees C. The antioxidant activity increased with lactoferrin concentration in both phosphate- and Tris-buffered emulsions, but not in both buffered liposome systems. A mixture of 1 microM lactoferrin and 0.5 microM ferrous ions was a significantly better antioxidant than 1 microM lactoferrin alone in Tris-buffered emulsions and in phosphate-buffered liposomes. Lactoferrin was a prooxidant at 1 microM in phosphate-buffered liposomes and at 15 and 20 microM in Tris-buffered liposomes. Copper was a stronger prooxidant than iron in both buffered emulsions. Lactoferrin decreased the prooxidant effect of iron, but not of copper, in emulsions. The antioxidant or prooxidant activities of lactoferrin depended on the lipid system, buffer, its concentration, the presence of metal ions, and oxidation time.

Animals↗

Comparison of natural polyphenol antioxidants from extra virgin olive oil with synthetic antioxidants in tuna lipids during thermal oxidation.

Polyphenols extracted from extra virgin olive oil (EVOO) were tested for their ability to inhibit lipid oxidation of canned tuna. Hydroperoxide formation during oxidation was monitored by measurement of peroxide value and decomposition of hydroperoxides by static headspace gas chromatographic analysis of volatiles. In tuna oxidized at 40 and 100 degrees C, 400 ppm of the EVOO polyphenols was an effective antioxidant as compared with 100 ppm of a 1:1 mixture of the synthetic antioxidants butylated hydroxytoluene and butylated hydroxyanisole. However, at concentrations <100 ppm, the EVOO phenolic compounds promoted hydroperoxide formation and decomposition. The EVOO polyphenols were effective antioxidants when added to heated tuna muscle in the presence of either brine or refined olive oil. The oxidation rate in tuna muscle packed in brine was higher than that of tuna packed in refined olive oil. The EVOO polyphenols had higher antioxidant activity in the brine samples than in the refined olive oil. The higher antioxidant activity of EVOO polyphenols in tuna packed in brine may be explained by their greater affinity toward the more polar interface between water and the fish oil system.

Animals↗

Catechin is present as metabolites in human plasma after consumption of red wine.

Flavonoids are components of fruits, vegetables and wines. An abundance of flavonoids in the diet is correlated with reduced heart disease mortality, suggesting that they act as protective nutrients. However, little is known about the absorption and metabolism of flavonoids after normal foods are consumed. This study measured the levels of one abundant flavonoid, (+)-catechin, and its metabolites in plasma after five male and four female volunteers consumed 120 mL of red wine (RW) one day and de-alcoholized red wine (DRW) on a separate day. Each wine sample contained 35 +/- 1 mg catechin (mean +/- SEM). Plasma levels of catechin and its metabolite 3'-O-methylcatechin (3'MC) were determined by gas chromatography-mass spectrometry (GC-MS) of the trimethylsilylated (TMS) derivatives. Glucuronide and sulfate conjugates were determined after enzymatic hydrolysis. Before RW or DRW consumption, plasma levels of catechin, 3'MC and all conjugates were <2 nmol/L. After 1 h, average levels of catechin, 3'MC and all conjugates increased to 91 +/- 14 nmol/L (RW) and 81 +/- 11 nmol/L (DRW). At 1 h, 21 +/- 1% of the metabolites were methylated and <2% of catechin and 3'MC were unconjugated. Catechin was present as both a sulfate conjugate and a conjugate containing both glucuronide and sulfate residues. 3'MC was present primarily as a glucuronide conjugate. At every time point, catechin was present almost exclusively as metabolites, and these levels were independent of ethanol. Therefore, if flavonoids are protective nutrients, the active forms are likely to be metabolites, which are far more abundant in plasma than the forms that exist in foods.

Adult↗