| 1. |
|
|
| 2. |
- de Mello, Vanessa D., et al.
(författare)
-
Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study
- 2017
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of alpha-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.
|
|
| 3. |
- Elo, Mika, et al.
(författare)
-
Differential regulation of stress proteins by high hydrostatic pressure, heat shock, and unbalanced calcium homeostasis in chondrocytic cells.
- 2000
-
Ingår i: Journal of Cellular Biochemistry. - : John Wiley & Sons. - 0730-2312 .- 1097-4644. ; 79:4, s. 610-619
-
Tidskriftsartikel (refereegranskat)abstract
- High hydrostatic pressure (HP) has recently been shown to increase cellular heat shock protein 70 (Hsp70) level in a specific way that does not involve transcriptional activation of the gene, but rather the stabilisation of the mRNA for Hsp70. In this study, we investigated whether there are other observable changes caused by HP stress, and compared them with those induced by certain other forms of stressors. A chondrocytic cell line T/C28a4 was exposed to 30 MPa continuous HP, heat shock at 43 degrees C, and increased cytosolic calcium concentration by the addition of sarco-endoplasmic reticulum Ca(2+) ATPase inhibitor thapsigargin (25 nM) or calcium ionophore A23187 (1 microM) in the cultures. The protein synthesis was studied by in vitro metabolic labelling followed by one- and two-dimensional polyacrylamide gel electrophoresis, and mass spectrometry was utilized to confirm the identity of the protein spots on two-dimensional gels. Continuous 30 MPa HP increased remarkably the relative labelling of Hsp70. Labelling of Hsp90 was also increased by 15-20%, although no clear change was evident at the protein level in Western blots. Elevated intracellular Ca(2+) concentration induced by thapsigargin and calcium ionophore A23187 increased mainly the synthesis of glucose-regulated protein 78 (Grp78/BiP), whereas Hsp70 and Hsp90 were decreased by the treatment. Heat shock was the strongest inducer of Hsp70 and Hsp90. This study further confirmed the induction of Hsp70 in chondrocytic cells exposed to high HP, but it also showed that calcium-mediated responses are unlikely to cause the stress response observed in the hydrostatically pressurized cells.
|
|
| 4. |
- Hanhineva, Kati, et al.
(författare)
-
Discovery of urinary biomarkers of whole grain rye intake in free-living subjects using non-targeted LC-MS metabolite profiling
- 2015
-
Ingår i: Molecular Nutrition & Food Research. - : Wiley. - 1613-4125 .- 1613-4133. ; 59:11, s. 2315-2325
-
Tidskriftsartikel (refereegranskat)abstract
- SCOPE: Whole grain (WG) intake is associated with decreased risk of developing colorectal cancer, type 2 diabetes and cardiovascular disease and its comorbidities. However, the role of specific grains is unclear. Moreover, intake of specific WG is challenging to measure accurately with traditional dietary assessment methods. Our aim was to use non-targeted metabolite profiling to discover specific urinary biomarkers for WG rye to objectively reflect intake under free-living conditions.METHODS AND RESULTS: WG rye intake was estimated by weighed food records, and 24 h urine collections were analyzed by LC-MS. Multivariate modelling was undertaken by repeated double cross-validated partial least squares regression against reported WG rye intake, which correlated well with multivariate prediction estimates (r = 0.67-0.80, p<0.001), but not with intakes of WG wheat or oats. Hydroxyhydroxyphenyl acetamide (HHPA) sulfate, 3,5-dihydroxyphenylpropionic acid (DHPPA) sulfate, caffeic acid sulfate and hydroxyphenyl acetamide (HPAA) sulfate were among the 20 features which had the greatest potential as intake biomarkers of WG. In addition, three compounds exhibited MS/MS fragmentation of carnitine structures.CONCLUSION: With this non-targeted approach, we confirmed the specificity of alkylresorcinol metabolites as biomarkers for WG rye intake, but also discovered other compounds that should be evaluated as putative biomarkers in future studies.
|
|
| 5. |
|
|
| 6. |
- Häkkinen, Katja, et al.
(författare)
-
Functional characterization of six SLCO1B1 (OATP1B1) variants observed in Finnish individuals with a psychotic disorder
- 2023
-
Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 20:3, s. 1500-1508
-
Tidskriftsartikel (refereegranskat)abstract
- Variants in the SLCO1B1 (solute carrier organic anion transporter family member 1B1) gene encoding the OATP1B1 (organic anion transporting polypeptide 1B1) protein are associated with altered transporter function that can predispose patients to adverse drug effects with statin treatment. We explored the effect of six rare SLCO1B1 single nucleotide variants (SNVs) occurring in Finnish individuals with a psychotic disorder on expression and functionality of the OATP1B1 protein. The SUPER-Finland study has performed exome sequencing on 9381 individuals with at least one psychotic episode during their lifetime. SLCO1B1 SNVs were annotated with PHRED-scaled combined annotation-dependent (CADD) scores and the Ensembl variant effect predictor. In vitro functionality studies were conducted for the SNVs with a PHRED-scaled CADD score of >10 and predicted to be missense. To estimate possible changes in transport activity caused by the variants, transport of 2′,7′-dichlorofluorescein (DCF) in OATP1B1-expressing HEK293 cells was measured. According to the findings, additional tests with rosuvastatin and estrone sulfate were conducted. The amount of OATP1B1 in crude membrane fractions was quantified using a liquid chromatography tandem mass spectrometry-based quantitative targeted absolute proteomics analysis. Six rare missense variants of SLCO1B1 were identified in the study population, located in transmembrane helix 3: c.317T>C (p.106I>T), intracellular loop 2: c.629G>T (p.210G>V), c.633A>G (p.211I>M), c.639T>A (p.213N>L), transmembrane helix 6: 820A>G (p.274I>V), and the C-terminal end: 2005A>C (p.669N>H). Of these variants, SLCO1B1 c.629G>T (p.210G>V) resulted in the loss of in vitro function, abolishing the uptake of DCF, estrone sulfate, and rosuvastatin and reducing the membrane protein expression to 31% of reference OATP1B1. Of the six rare missense variants, SLCO1B1 c.629G>T (p.210G>V) causes a loss of function of OATP1B1 transport in vitro and severely decreases membrane protein abundance. Carriers of SLCO1B1 c.629G>T might be susceptible to altered pharmacokinetics of OATP1B1 substrate drugs and might have increased likelihood of adverse drug effects such as statin-associated musculoskeletal symptoms.
|
|
| 7. |
- Keski-Rahkonen, Pekka, et al.
(författare)
-
Fast and sensitive liquid chromatography-mass spectrometry assay for seven androgenic and progestagenic steroids in human serum.
- 2011
-
Ingår i: The Journal of steroid biochemistry and molecular biology. - : Elsevier BV. - 1879-1220 .- 0960-0760. ; 127:3-5, s. 396-404
-
Tidskriftsartikel (refereegranskat)abstract
- A fast and sensitive LC-MS/MS method for the quantitative analysis of seven steroid hormones in 150 μl of human serum was developed and validated. The following compounds were included: 17α-hydroxypregnenolone, 17α-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, testosterone, pregnenolone, and progesterone. Individual stable isotope-labeled analogues were used as internal standards. Sample preparation was performed by liquid-liquid extraction, followed by oxime derivatization to improve the ionization efficiency of the analytes. In contrast to the common derivatization-based methods, the reaction was incorporated into the sample preparation process and the only additional step due to the derivatization was a short heating of the autosampler vials before the sample injection. Chromatographic separation was achieved on a reversed-phase column using a methanol-water gradient. For the analyte detection, a triple quadrupole instrument with electrospray ionization was used. Total run time was 7.0 min and the lower limits of quantification were in the range of 0.03-0.34 nM (0.01-0.10 ng/ml), depending on the analyte. The method was validated using human serum samples from both sexes and applied for the serum steroid profiling of endometriosis patients.
|
|
| 8. |
- Knuuttila, Matias, et al.
(författare)
-
Antiandrogens Reduce Intratumoral Androgen Concentrations and Induce Androgen Receptor Expression in Castration-Resistant Prostate Cancer Xenografts.
- 2018
-
Ingår i: The American journal of pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 188:1, s. 216-228
-
Tidskriftsartikel (refereegranskat)abstract
- The development of castration-resistant prostate cancer (CRPC) is associated with the activation of intratumoral androgen biosynthesis and an increase in androgen receptor (AR) expression. We recently demonstrated that, similarly to the clinical CRPC, orthotopically grown castration-resistant VCaP (CR-VCaP) xenografts express high levels of AR and retain intratumoral androgen concentrations similar to tumors grown in intact mice. Herein, we show that antiandrogen treatment (enzalutamide or ARN-509) significantly reduced (10-fold, P<0.01) intratumoral testosterone and dihydrotestosterone concentrations in the CR-VCaP tumors, indicating that the reduction in intratumoral androgens is a novel mechanism by which antiandrogens mediate their effects in CRPC. Antiandrogen treatment also altered the expression of multiple enzymes potentially involved in steroid metabolism. Identical to clinical CRPC, the expression levels of the full-length AR (twofold, P<0.05) and the AR splice variants 1 (threefold, P<0.05) and 7 (threefold, P<0.01) were further increased in the antiandrogen-treated tumors. Nonsignificant effects were observed in the expression of certain classic androgen-regulated genes, such as TMPRSS2 and KLK3, despite the low levels of testosterone and dihydrotestosterone. However, other genes recently identified to be highly sensitive to androgen-regulated AR action, such as NOV and ST6GalNAc1, were markedly altered, which indicated reduced androgen action. Taken together, the data indicate that, besides blocking AR, antiandrogens modify androgen signaling in CR-VCaP xenografts at multiple levels.
|
|
| 9. |
- Koistinen, Ville Mikael, et al.
(författare)
-
Side-stream products of malting: a neglected source of phytochemicals
- 2020
-
Ingår i: npj Science of Food. - : Springer Science and Business Media LLC. - 2396-8370. ; 4:1
-
Tidskriftsartikel (refereegranskat)abstract
- Whole grain consumption reduces the risk of several chronic diseases. A major contributor to the effect is the synergistic and additive effect of phytochemicals. Malting is an important technological method to process whole grains; the main product, malted grain, is used mainly for brewing, but the process also yields high amounts of side-stream products, such as rootlet. In this study, we comprehensively determined the phytochemical profile of barley, oats, rye, and wheat in different stages of malting and the subsequent extraction phases to assess the potential of malted products and side-streams as a dietary source of bioactive compounds. Utilizing semi-quantitative LC–MS metabolomics, we annotated 285 phytochemicals from the samples, belonging to more than 13 chemical classes. Malting significantly altered the levels of the compounds, many of which were highly increased in the rootlet. Whole grain cereals and the malting products were found to be a diverse and rich source of phytochemicals, highlighting the value of these whole foods as a staple. The characterization of phytochemicals from the 24 different sample types revealed previously unknown existence of some of the compound classes in certain species. The rootlet deserves more attention in human nutrition, rather than its current use mainly as feed, to benefit from its high content of bioactive components.
|
|
| 10. |
- Puris, Elena, et al.
(författare)
-
Mechanistic Study on the Use of the L-Type Amino Acid Transporter 1 for Brain Intracellular Delivery of Ketoprofen via Prodrug : A Novel Approach Supporting the Development of Prodrugs for Intracellular Targets
- 2019
-
Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 16:7, s. 3261-3274
-
Tidskriftsartikel (refereegranskat)abstract
- L-Type amino acid transporter 1 (LAT1), selectively expressed at the blood-brain barrier (BBB) and brain parenchymal cells, mediates brain delivery of drugs and prodrugs such as L-dopa and gabapentin. Although knowledge about BBB transport of LAT1-utilizing prodrugs is available, there is a lack of quantitative information about brain intracellular delivery and influence of prodrugs on the transporter's physiological state. We studied the LAT1-mediated intrabrain distribution of a recently developed prodrug of the cyclooxygenase inhibitor ketoprofen as well as its impact on transporter protein expression and function (i.e., amino acid exchange) using brain slice method in mice and rats. The intrabrain distribution of the prodrug was 16 times higher than that of ketoprofen. LAT1 involvement in brain cellular barrier uptake of the prodrug was confirmed, reflected by a higher unbound brain intracellular compared to brain extracellular fluid concentration. The prodrug did not alter LAT1 protein expression and amino acid exchange. Integration of derived parameters with previously performed in vivo pharmacokinetic study using the Combinatory Mapping Approach allowed to estimate the brain extra- and intracellular levels of unbound ketoprofen, prodrug, and released parent drug. The overall efficiency of plasma to brain intracellular delivery of prodrug-released ketoprofen was 11 times higher than after ketoprofen dosing. In summary, this study provides quantitative information supporting the use of the LAT1-mediated prodrug approach for enhanced brain delivery of drugs with intracellular targets.
|
|
| 11. |
- Qu, Cheng-Juan, 1967-, et al.
(författare)
-
Effects of glucosamine sulfate on intracellular UDP-hexosamine and UDP-glucuronic acid levels in bovine primary chondrocytes.
- 2007
-
Ingår i: Osteoarthritis and Cartilage. - : Saunders Elsevier. - 1063-4584 .- 1522-9653. ; 15:7, s. 773-779
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the effects of exogenously added glucose (Glc), glucosamine (GlcN) and glucosamine sulfate (GS) on the intracellular UDP-hexoses (UDP-Hex), UDP-N-acetylhexosamines (UDP-HexN) and UDP-glucuronic acid (UDP-GlcA) levels in bovine primary chondrocytes.METHODS: Chondrocytes were incubated with different concentrations of Glc, GlcN and GS either in high- or low-glucose DMEM for up to 120min to analyze the intracellular levels of UDP-Hex, UDP-GlcA and UDP-HexN by a reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry analysis. Glycosaminoglycan (GAG) synthesis rate and aggrecan mRNA expression levels were quantified using (35)S-sulfate incorporation assay and quantitative real-time RT-PCR, respectively. The cells were cultivated for 2 days or 8 days before UDP-sugar analysis.RESULTS: Levels of UDP-HexN and UDP-GlcA were unchanged at 10microM concentration of GS in low-glucose DMEM, while addition of 1mM GlcN or GS in low-glucose DMEM for 10min increased UDP-HexN level. The highest intracellular level of UDP-HexN was reached at 30min after addition of 1mM GS to the cells. The intracellular contents of UDP-HexN and UDP-GlcA related to UDP-Hex were higher after prolonged cultivation of chondrocytes for 8 days compared with 2-day-old cultures. Aggrecan mRNA expression and GAG synthesis remained at control level after the cells were treated with 10, 100microM or 1mM of GS for 24h.CONCLUSION: Physiologically relevant level of GS could not increase the intracellular UDP-HexN and UDP-GlcA levels in bovine primary chondrocyte, while longer-time culture itself appeared to increase the intracellular UDP-HexN and UDP-GlcA levels.
|
|
| 12. |
- Qu, Cheng-Juan, 1967-, et al.
(författare)
-
Glucosamine sulphate does not increase extracellular matrix production at low oxygen tension.
- 2009
-
Ingår i: Cell and Tissue Research. - : Springer. - 0302-766X .- 1432-0878. ; 337:1, s. 103-111
-
Tidskriftsartikel (refereegranskat)abstract
- Low oxygen tension may change the dependence of chondrocytes on exogenous carbohydrate sources. In this study, we have investigated whether glucosamine sulphate (GS) stimulates proteoglycan synthesis, the mRNA expression of aggrecan and of type II collagen, and UDP-sugar levels in bovine primary chondrocytes under a low oxygen (O(2)) atmosphere. Chondrocytes from bovine femoral condyles were cultivated with or without GS or sulphate at various concentrations in low- (5.5 mM) or high-glucose (25 mM) DMEM under either a 5% or 20% O(2) atmosphere for 2 or 8 days after isolation. The mRNA expression of aggrecan and type II collagen and the synthesis of glycosaminoglycan (GAG) were determined by quantitative real-time reverse transcription with polymerase chain reaction and a [(35)S]-sulphate incorporation assay, respectively. Aggrecan promoter activity was analysed by a dual-luciferase reporter gene assay. Intracellular UDP-N-acetylhexosamines (UDP-HexN), UDP-glucuronic acid and UDP-hexoses were analysed by reversed-phase high-performance liquid chromatography electrospray ionization mass spectrometry. A low (5%) O(2) atmosphere significantly increased GAG synthesis, mRNA expression of aggrecan and of type II collagen and aggrecan promoter activity in bovine primary chondrocytes. A high (1 mM) concentration of GS was required to increase the level of UDP-HexN. However, GS did not increase GAG synthesis, aggrecan promoter activity or mRNA expression of aggrecan and of type II collagen. Interestingly, a 5% O(2) atmosphere increased the level of UDP-HexN in 8-day cultures without GS treatment. Thus, exogenous GS does not change chondrocyte metabolism, whereas a 5% O(2) atmosphere stimulates extracellular matrix production in bovine primary chondrocytes. The balance of UDP-sugars is changed under a 5% O(2) atmosphere for longer culture periods.
|
|
| 13. |
- Shi, Lin, 1988, et al.
(författare)
-
Plasma metabolites associated with type 2 diabetes in a Swedish population: a case-control study nested in a prospective cohort
- 2018
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 61:4, s. 849-861
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The aims of the present work were to identify plasma metabolites that predict future type 2 diabetes, to investigate the changes in identified metabolites among individuals who later did or did not develop type 2 diabetes over time, and to assess the extent to which inclusion of predictive metabolites could improve risk prediction. Methods We established a nested case-control study within the Swedish prospective population-based Vasterbotten Intervention Programme cohort. Using untargeted liquid chromatography-MS metabolomics, we analysed plasma samples from 503 case-control pairs at baseline (a median time of 7 years prior to diagnosis) and samples from a subset of 187 case-control pairs at 10 years of follow-up. Discriminative metabolites between cases and controls at baseline were optimally selected using a multivariate data analysis pipeline adapted for large-scale metabolomics. Conditional logistic regression was used to assess associations between discriminative metabolites and future type 2 diabetes, adjusting for several known risk factors. Reproducibility of identified metabolites was estimated by intra-class correlation over the 10 year period among the subset of healthy participants; their systematic changes over time in relation to diagnosis among those who developed type 2 diabetes were investigated using mixed models. Risk prediction performance of models made from different predictors was evaluated using area under the receiver operating characteristic curve, discrimination improvement index and net reclassification index. Results We identified 46 predictive plasma metabolites of type 2 diabetes. Among novel findings, phosphatidylcholines (PCs) containing odd-chain fatty acids (C19: 1 and C17:0) and 2-hydroxyethanesulfonate were associated with the likelihood of developing type 2 diabetes; we also confirmed previously identified predictive biomarkers. Identified metabolites strongly correlated with insulin resistance and/or beta cell dysfunction. Of 46 identified metabolites, 26 showed intermediate to high reproducibility among healthy individuals. Moreover, PCs with odd-chain fatty acids, branched-chain amino acids, 3-methyl-2-oxovaleric acid and glutamate changed over time along with disease progression among diabetes cases. Importantly, we found that a combination of five of the most robustly predictive metabolites significantly improved risk prediction if added to models with an a priori defined set of traditional risk factors, but only a marginal improvement was achieved when using models based on optimally selected traditional risk factors. Conclusions/interpretation Predictive metabolites may improve understanding of the pathophysiology of type 2 diabetes and reflect disease progression, but they provide limited incremental value in risk prediction beyond optimal use of traditional risk factors.
|
|
| 14. |
- Tuomainen, Marjo, et al.
(författare)
-
Quantitative assessment of betainized compounds and associations with dietary and metabolic biomarkers in the randomized study of the healthy Nordic diet (SYSDIET)
- 2019
-
Ingår i: American Journal of Clinical Nutrition. - : OXFORD UNIV PRESS. - 0002-9165 .- 1938-3207. ; 110:5, s. 1108-1118
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Recently, a group of betainized compounds have been suggested to play a role in health effects in relation to a whole-grain-rich diet.Objectives: The aims of this study were to develop a quantitative mass spectrometric method for selected betainized compounds in human plasma, and to investigate their association with nutrient intake and measures of metabolic health in participants of the SYSDIET study.Methods: The SYSDIET study was a controlled randomized intervention including individuals with metabolic syndrome, where the healthy Nordic diet (HND) group increased intakes of whole grains, canola oil, berries, and fish, whereas the control diet (CD) group consumed low-fiber cereal products, milk fat, and restricted amounts of fish and berries. A quantitative LC combined with triple quadrupole MS method for betainized compounds was developed and applied to fasting plasma samples from baseline (week 0) and the end of the intervention (week 18 or 24). Concentrations of betainized compounds were correlated with intakes of selected nutrients and fiber and measures of metabolic health.Results: Pipecolic acid betaine (PAB) concentrations were significantly higher in the HND group than in the CD group (P = 0.00032) at the end of the intervention and correlated directly (P < 0.0001) with intakes of dietary fiber (r = 0.376) and a biomarker related to whole-grain rye intake, namely the ratio of alkylresorcinol C17:0 to C21:0 (r = 0.442). PAB was associated inversely with fasting plasma insulin consistently at the beginning and at the end of the intervention (P < 0.001, r = -0.300; P < 0.01, r = -0.250, respectively), as well as IL-1 receptor antagonist (P < 0.01, r = -0.232 at the beginning; P < 0.01, r = -0.236 at the end) and serum LDL/HDL cholesterol (P < 0.01, r = -0.239 at the beginning; P < 0.01, r = -0.241 at the end).Conclusions: Among adults with the metabolic syndrome, PAB plasma concentrations were associated with fasting insulin, inflammation, and lipids and were significantly increased with adoption of the HND. Further studies are needed to clarify the biological functions of betainized compounds.
|
|
| 15. |
- Vitale, Marilena, et al.
(författare)
-
Putative metabolites involved in the beneficial effects of wholegrain cereal: Nontargeted metabolite profiling approach
- 2021
-
Ingår i: Nutrition, Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 31:4, s. 1156-1165
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Wholegrain cereals have been implicated in the reduction of lifestyle-related chronic diseases risk including cardiovascular diseases and type 2 diabetes. Molecular mechanisms responsible for the beneficial health effects are not entirely understood. The aims of this study were 1) to identify new potential plasma biomarker candidate metabolites of wholegrain cereal foods intake and 2) to examine whether some putative metabolites associated with wholegrain foods intake may play a role in the improvement of cardiometabolic risk factors. Methods and results: Analysis have been conducted in 54 individuals with metabolic syndrome of both genders, age 40–65 years, randomly assigned to 2 dietary interventions lasting 12-week: 1) wholegrain enriched diet (n = 28), and 2) refined-wheat cereals diet (control diet) (n = 26). Nontargeted metabolite profiling analysis was performed on fasting plasma samples collected at baseline and at the end of the experimental diets. Our data show that, at the end of the intervention, a higher intake of wholegrain (tertile 3) was significantly associated with a marked increase in several lipid compounds, as PC (20:4/16:1), LPC (20:4), LPC (22:6), LPC (18:3), LPC (22:5), and a phenolic compound (P < .05 for all). In the wholegrain group, higher concentrations of these metabolites (tertile 3 vs tertile 1 of each metabolite) were significantly associated with lower postprandial insulin and triglyceride responses (P < .05) by 29% and 37%, respectively. Conclusion: These observations suggest a possible role of lipid and polyphenol metabolites in the postprandial metabolic benefits of wholegrains in subjects at high risk of cardiovascular disease. In addition, they provide insight into the role of these metabolites as potential candidate biomarkers of wholegrain foods. The study was registered on ClinicalTrials.gov (identifier: NCT00945854).
|
|
