Gaby Andersen

Quantitation of alpha-linolenic acid elongation to eicosapentaenoic and docosahexaenoic acid as affected by the ratio of n6/n3 fatty acids

BackgroundConversion of linoleic acid (LA) and alpha-linolenic acid (ALA) to their higher chain homologues in humans depends on the ratio of ingested n6 and n3 fatty acids.Design and methodsIn order to determine the most effective ratio with regard to the conversion of ALA to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), human hepatoma cells were incubated with varying ratios of [13C] labeled linoleic acid ([13C]LA)- and alpha-linolenic acid ([13C]ALA)-methylesters. Regulative cellular signal transduction pathways involved were studied by determinations of transcript levels of the genes encoding delta-5 desaturase (D5D) and delta-6 desaturase (D6D), peroxisome proliferator-activated receptor alpha (PPARα) and sterol regulatory element binding protein 1c (SREBP-1c). Mitogen-activated protein kinase kinase 1 (MEK1) and mitogen-activated protein kinase kinase kinase 1 (MEKK1) were also examined.ResultsMaximum conversion was observed in cells incubated with the mixture of [13C]LA/[13C]ALA at a ratio of 1:1, where 0.7% and 17% of the recovered [13C]ALA was converted to DHA and EPA, respectively. Furthermore, differential regulation of enzymes involved in the conversion at the transcript level, dependent on the ratio of administered n6 to n3 fatty acids in human hepatocytes was demonstrated.ConclusionFormation of EPA and DHA was highest at an administered LA/ALA ratio of 1:1, although gene expression of PPARα, SREBP-1c and D5D involved in ALA elongation were higher in the presence of ALA solely. Also, our findings suggest that a diet-induced enhancement of the cell membrane content of highly unsaturated fatty acids is only possible up to a certain level.

Interactions of the advanced glycation end product inhibitor pyridoxamine and the antioxidant α-lipoic acid on insulin resistance in the obese Zucker rat

Oxidative stress and protein glycation can contribute to the development of insulin resistance and complications associated with type 2 diabetes mellitus. The antioxidant alpha-lipoic acid (ALA) reduces oxidative stress and the formation of advanced glycation end products (AGEs) and improves insulin sensitivity in skeletal muscle and liver. The AGE inhibitor pyridoxamine (PM) prevents irreversible protein glycation, thereby reducing various diabetic complications. The potential interactive effects of ALA and PM in the treatment of whole-body and skeletal muscle insulin resistance have not been investigated. Therefore, this study was designed to determine the effects of combined ALA and PM treatments on reducing muscle oxidative stress and ameliorating insulin resistance in prediabetic obese Zucker rats. Obese Zucker rats were assigned to either a control group or to a treatment group receiving daily injections of the R-(+)-enantiomer of ALA (R-ALA, 92 mg/kg) or PM (60 mg/kg), individually or in combination, for 6 weeks. The individual and combined treatments with R-ALA and PM were effective in significantly (P < .05) reducing plantaris muscle protein carbonyls (33%-40%) and urine-conjugated dienes (22%-38%), markers of oxidative stress. The R-ALA and PM in combination resulted in the largest reductions of fasting plasma glucose (23%), insulin (16%), and free fatty acids (24%) and of muscle triglycerides (45%) compared with alterations elicited by individual treatment with R-ALA or PM. Moreover, the combination of R-ALA and PM elicited the greatest enhancement of whole-body insulin sensitivity both in the fasted state and during an oral glucose tolerance test. Finally, combined R-ALA/PM treatments maintained the 44% enhancement of in vitro insulin-mediated glucose transport activity in soleus muscle of obese Zucker rats treated with R-ALA alone. Collectively, these results document a beneficial interaction of the antioxidant R-ALA and the AGE inhibitor PM in the treatment of whole-body and skeletal muscle insulin resistance in obese Zucker rats.

Dietary Eicosapentaenoic Acid and Docosahexaenoic Acid Are More Effective than Alpha-Linolenic Acid in Improving Insulin Sensitivity in Rats

In the present study, we investigated whether long-term administration of high dose of α-linolenic acid (ALA) is able to mimic the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or a mixture of both with respect to insulin sensitivity in male Wistar rats. Furthermore, we intended to test whether these n–3 polyunsaturated fatty acids reveal differential effects on glucose and insulin levels. As a result, plasma glucose and insulin levels were lowered by 35 and 38%, respectively, in the EPA and DHA group compared to the ALA group. Insulin sensitivity was substantially improved, as indicated by a 60% decreased HOMA index after an 8-week EPA and DHA administration, as compared to the effect observed for feeding ALA. However, insulin sensitivity did not differ between animals of the EPA and the DHA group. These results demonstrate that ALA intake at the expense of EPA and DHA in a diet high in n–3 fatty acids does not represent an alternative to raising oily fish consumption with regard to insulin sensitivity. Furthermore, a differential effect of the members of the n–3 family was shown for ALA compared to EPA and DHA, but EPA and DHA revealed comparable effects on insulin sensitivity.

Effects of Dietary α-Linolenic Acid, Eicosapentaenoic Acid or Docosahexaenoic Acid on Parameters of Glucose Metabolism in Healthy Volunteers

Aim: To investigate the effects of α-linolenic acid (ALA) and purified eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on fasting concentrations of glucose, insulin, fructosamine, on glycosylated haemoglobin (HbA1c) and on insulin sensitivity. Methods: A randomized strictly controlled dietary study in 48 healthy volunteers (13 males, 35 females) of normal body weight (mean age 25.9 years) with three dietary groups (ALA, EPA and DHA) and a parallel design, consisting of two consecutive periods. Subjects received a 2-week wash-in diet rich in monounsaturated fatty acids followed by experimental diets enriched with equal amounts of ALA, EPA, or DHA for 3 weeks. Mean dietary intake of ALA in the ALA group was 6.0 g/day (2.5% of energy intake), mean intake of EPA in the EPA group was 2.8 g/day (1.1% of energy intake) and mean intake of DHA in the DHA group was 2.9 g/day (1.1% of energy intake). Results: Fasting serum concentrations of insulin and fructosamine and of HbA1c did not change significantly after consuming the ALA, EPA or DHA diet. Fasting serum glucose levels did not change significantly following either the ALA or DHA diet. During the EPA diet, fasting glucose concentration slightly increased by 0.15 mmol/l (p < 0.05). All measured values of all subjects were in the reference ranges for healthy adults. No effects on insulin sensitivity indicated by the HOMA insulin resistance index could be observed. Conclusions: Except for the minor effect of EPA on fasting glucose levels, the moderate amounts of dietary ALA, EPA or DHA administered in this study did not significantly affect blood concentrations of glucose, insulin, fructosamine and HbA1c in healthy normal-weight men and women over a time course of 3 weeks.

High dose of dietary resveratrol enhances insulin sensitivity in healthy rats but does not lead to metabolite concentrations effective for SIRT1 expression

SCOPE trans-Resveratrol has been shown to improve insulin sensitivity and to enhance cellular glucose uptake. Evidence from recent studies indicates that these effects depend on SIRT1-pathways. METHODS AND RESULTS Since ingestion of resveratrol leads to the presence of resveratrol and resveratrol metabolites in the body, we aimed at investigating (i) whether a daily dose of 300 mg resveratrol/kg body weight in healthy male Wistar rats for a period of 8 wk affects the selected parameters of glucose and lipid metabolism and (ii) whether the resulting plasma concentrations of resveratrol metabolites were effective in modulating SIRT1 expression. The dietary dose was based on the results from preceding toxicity studies. The results from the feeding experiment revealed plasma concentrations of resveratrol and its metabolites below 1 μmol/L and showed that fasting glucose and insulin levels were decreased by 35 and 41%, respectively, in the resveratrol group compared with controls. Insulin sensitivity was enhanced by 70%, whereas liver SIRT1 protein expression was not affected. Treatment of HepG2 cells with 10 μM resveratrol (1.49-fold) or its diglucuronides (1.21-fold) increased SIRT1 expression. CONCLUSION These results suggest that the improved insulin sensitivity after dietary administration of 300 mg resveratrol/kg body weight does not involve increased protein expression of SIRT1.

Heat Treatment of Brussels Sprouts Retains Their Ability to Induce Detoxification Enzyme Expression In Vitro and In Vivo

UNLABELLED The bioactive metabolites of glucosinolates, such as isothiocyanates, contained in cruciferous vegetables have been shown to reduce the risk of cancers through the induction of detoxification enzymes. However, cruciferous vegetables are commonly processed before consumption, significantly altering the phytochemical composition of these vegetables. Compared to freeze-dried Brussels sprouts, oven-dried Brussels sprouts contain low concentrations of glucosinolates (22.14 and 0.85 μmol/g, respectively) and isothiocyanates (3.68 and 0.15 μmol/g, respectively). The effect of oven-dried Brussels sprouts on the expression of detoxification enzymes was evaluated in vitro and in vivo. Treatment of immortalized human hepatoma cells with the aqueous extract from oven-dried Brussels sprouts significantly increased quinone activity (0.5 and 1.5 mg/mL) and the activity of the antioxidant response element (EC50=2.39 mg/mL) and xenobiotic response element (EC50 2.92 mg/mL). C3H/HeJ mice fed a diet containing 20% oven-dried Brussels sprout diets for 2 wk demonstrated significantly higher expression than animals fed a nutrient-matched control diet of CYP1A1, CYP1A2, and epoxide hydrolase in the liver and CYP1A1, CYP1A2, CYP1B1, epoxide hydrolase, UGT1A1, thioredoxin reductase, and heme oxygenase in the lungs. The low concentrations of glucosinolates and isothiocyanates in oven-dried Brussels sprouts suggest that other compounds, such as the Maillard reaction products that are produced during heating, are responsible for the induction of detoxification enzymes in vitro and in vivo. PRACTICAL APPLICATION   The manner in which cruciferous vegetables are processed prior to consumption has significant effects on what compounds people are exposed to. The presence of glucosinolates or isothiocyanates can be a good indicator of the ability of cruciferous vegetables to induce detoxification enzymes. However, the data presented here demonstrate that while heat processing of Brussels sprouts greatly reduced the concentrations of glucosinolates and isothiocyanates, their ability to induce detoxification enzymes in vitro and in vivo was retained.

Metabolic Effects of Bread Fortified with Wheat Sprouts and Bioavailability of Ferulic Acid from Wheat Bran

Publisher Summary Wheat is the principal cereal used in the preparation of a variety of bakery products. Utilization of germinated wheat in bakery products can involve both field-sprouted and intentionally or artificially germinated wheat. More than 15% of wheat produced suffers from field sprouting. The flours obtained from grains sprouted in the field have been shown to have detrimental effects on dough and bread properties and on pasta products. By using wheat sprouts that had been germinated for only 4.25 days (102 h), an edible product with good baking and sensory qualities is obtained. The beneficial health effects of wheat sprouts may be due to not only the fiber content but also the high amount of phenolic compounds. The health-promoting effects range from antioxidant functions to glucose-lowering effects. However, because the bioavailability of phenolic compounds from grains is very low, strategies have to be developed to enhance their natural bioavailability.

Effect of 1- and 2-Month High-Dose Alpha-Linolenic Acid Treatment on 13C-Labeled Alpha-Linolenic Acid Incorporation and Conversion in Healthy Subjects

Scope The study aims at identifying 1) the most sensitive compartment among plasma phospholipids, erythrocytes, and LDL for studying alpha‐linolenic acid (ALA) conversion, and 2) whether ALA incorporation and conversion is saturable after administration of 13C‐labeled ALA‐rich linseed oil (LO). The effect of a daily intake of 7 g nonlabeled LO (>43% w/w ALA) for 1 month after bolus administration of 7 g 13C‐labeled LO on day 1, and for 2 months after bolus administration of 7 g 13C‐labeled LO on day 1 and day 29 on 13C‐ALA incorporation and conversion into its higher homologs is investigated in healthy volunteers. Methods and results Incorporation and conversion of LO‐derived 13C‐labeled ALA is quantified by applying compartmental modeling. After bolus administration, a fractional conversion of approximately 30% from 13C‐ALA to 13C‐DHA is calculated as reflected by the LDL compartment. Treatment with LO for 8 weeks induces a mean reduction of 13C‐ALA conversion to 13C‐DHA by 48% as reflected by the LDL compartment, and a mean reduction of the 13C‐ALA incorporation into LDL by 46%. Conclusion A 2‐month dietary intake of a high dose of LO is sufficient to reach saturation of ALA incorporation into LDL particles, which are responsible for ALA distribution in the body.