Browsing by Subject "LIPIDS"

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  • Surakka, Ida; Isaacs, Aaron; Karssen, Lennart C.; Laurila, Pirkka-Pekka P.; Middelberg, Rita P. S.; Tikkanen, Emmi; Ried, Janina S.; Lamina, Claudia; Mangino, Massimo; Igl, Wilmar; Hottenga, Jouke-Jan; Lagou, Vasiliki; van der Harst, Pim; Leach, Irene Mateo; Esko, Tonu; Kutalik, Zoltan; Wainwright, Nicholas W.; Struchalin, Maksim V.; Sarin, Antti-Pekka; Kangas, Antti J.; Viikari, Jorma S.; Perola, Markus; Rantanen, Taina; Petersen, Ann-Kristin; Soininen, Pasi; Johansson, Asa; Soranzo, Nicole; Heath, Andrew C.; Papamarkou, Theodore; Prokopenko, Inga; Toenjes, Anke; Kronenberg, Florian; Doering, Angela; Rivadeneira, Fernando; Montgomery, Grant W.; Whitfield, John B.; Kahonen, Mika; Lehtimaki, Terho; Freimer, Nelson B.; Willemsen, Gonneke; de Geus, Eco J. C.; Palotie, Aarno; Sandhu, Manj S.; Waterworth, Dawn M.; Metspalu, Andres; Stumvoll, Michael; Uitterlinden, Andre G.; Jula, Antti; Navis, Gerjan; Wijmenga, Cisca; Wolffenbuttel, Bruce H. R.; Taskinen, Marja-Riitta; Ala-Korpela, Mika; Kaprio, Jaakko; Kyvik, Kirsten O.; Boomsma, Dorret I.; Pedersen, Nancy L.; Gyllensten, Ulf; Wilson, James F.; Rudan, Igor; Campbell, Harry; Pramstaller, Peter P.; Spector, Tim D.; Witteman, Jacqueline C. M.; Eriksson, Johan G.; Salomaa, Veikko; Oostra, Ben A.; Raitakari, Olli T.; Wichmann, H. -Erich; Gieger, Christian; Jaervelin, Marjo-Riitta; Martin, Nicholas G.; Hofman, Albert; McCarthy, Mark I.; Palotie, Leena; van Duijn, Cornelia M.; Aulchenko, Yurii S.; Ripatti, Samuli (2011)
  • Tverin, Malin; Granroth, Janne; Abrahamsson, Alexander; Tang, Patrik Anthony; Pihlström, Henry; Lundström, Karl; Käkelä, Reijo (2021)
    Increased numbers of great cormorants (Phalacrocorax carbo) in the Baltic Sea may have local impacts on fisheries and salmonid hatcheries. We studied spatial and temporal variability in cormorant diet, and potential consumption of hatchery salmonids, by analysing knee subcutaneous adipose tissue fatty acids (FA) of specimens (N = 77) collected along Swedish and Finnish coasts in different seasons during 2013–2017. The FA profiles of the subspecies sinensis and carbo were similar, with large individual variation. The proportion of C18 polyunsaturated FAs (PUFAs) was the largest in the north, whereas the proportion of C20–22 monounsaturated FAs (MUFAs) increased towards the south, reflecting diminishing freshwater and increasing marine food web characteristics towards the south. As an exception, the C20–22 MUFA percentage was high in sinensis collected in June 2017 from the northern Baltic Sea. The source of C20–22 MUFAs was probably hatchery salmonids, raised on ocean fish hatchery feed and released 10 days before, near the cormorant capture site. The FA profiles of northern and southern cormorants differed from each other both in early and late summer samples, suggesting spatially different diets. The largest individual variation was found in 22:1n-11, characteristic of ocean zooplanktivorous fish, and likely originating from Atlantic wild or Baltic Sea hatchery-reared fish. This study shows that adipose tissue FA profiles can be used as proxies for seabird diet monitoring and indicators of predation on hatchery-reared fish. Obtaining quantitative estimates on the proportions of dietary fish species requires future feeding experiments, allowing calibration between the FA compositions and diet.
  • Helkkula, Pyry; Kiiskinen, Tuomo; Havulinna, Aki S.; Karjalainen, Juha; Koskinen, Seppo; Salomaa, Veikko; Daly, Mark; Palotie, Aarno; Surakka, Ida; Ripatti, Samuli (2021)
    Protein-truncating variants (PTVs) affecting dyslipidemia risk may point to therapeutic targets for cardiometabolic disease. Our objective was to identify PTVs that were associated with both lipid levels and the risk of coronary artery disease (CAD) or type 2 diabetes (T2D) and assess their possible associations with risks of other diseases. To achieve this aim, we leveraged the enrichment of PTVs in the Finnish population and tested the association of low-frequency PTVs in 1,209 genes with serum lipid levels in the Finrisk Study (n = 23,435). We then tested which of the lipid-associated PTVs were also associated with the risks of T2D or CAD, as well as 2,683 disease endpoints curated in the FinnGen Study (n = 218,792). Two PTVs were associated with both lipid levels and the risk of CAD or T2D: triglyceride-lowering variants in ANGPTL8 (-24.0[-30.4 to -16.9] mg/dL per rs760351239-T allele, P = 3.4 x 10(-9)) and ANGPTL4 (-14.4[-18.6 to -9.8] mg/dL per rs746226153-G allele, P = 4.3 x 10(-9)). The risk of T2D was lower in carriers of the ANGPTL4 PTV (OR = 0.70[0.60-0.81], P = 2.2 x 10(-6)) than noncarriers. The odds of CAD were 47% lower in carriers of a PTV in ANGPTL8 (OR = 0.53[0.37-0.76], P = 4.5 x 10(-4)) than noncarriers. Finally, the phenome-wide scan of the ANGPTL8 PTV showed that the ANGPTL8 PTV carriers were less likely to use statin therapy (68,782 cases, OR = 0.52[0.40-0.68], P = 1.7 x 10(-6)) compared to noncarriers. Our findings provide genetic evidence of potential long-term efficacy and safety of therapeutic targeting of dyslipidemias. Author summary Studying the health impacts of protein-truncating variants (PTVs) enables detecting the health impact of drugs that inhibit these same genes. Our study aimed to expand our knowledge of genes associated with cardiometabolic disease, along with the side effects of these genes. To detect PTVs associated with cardiometabolic disease, we first performed a genome-wide scan of PTVs associated with serum lipid levels in Finns. We found PTVs in two genes highly enriched in Finns, which were associated with both serum lipid levels and a lower risk of type 2 diabetes or coronary artery disease: ANGPTL4 and ANGPTL8. To evaluate the other health effects of these PTVs, we performed an association scan between the PTVs and 2,683 disease endpoints curated in the FinnGen Study (n = 218,792). We demonstrate that using human populations with PTV-enrichment, such as Finns, offers considerable boosts in statistical power to detect potential long-term efficacy and safety of pharmacologically targeting genes.
  • Malkamäki, Aapo Erkki Matias; Sharma, Vivek (2019)
    Mitochondrial cytochrome c oxidase couples the reduction of oxygen to proton pumping. Despite an overall good understanding of its molecular mechanism, the role of cardiolipin in protein function is not understood. Here, we have studied the cardiolipin-protein interactions in a dynamic context by means of atomistic molecular dynamics simulations performed on the entire structure of monomeric and dimeric forms of the enzyme. Several microseconds of simulation data reveal that the crystallographic cardiolipin molecules that glue two monomers together bind weakly in hybrid and single-component lipid bilayers and dissociate rapidly. Atomistic simulations performed in the absence of tightly bound cardiolipin molecules strongly perturb the structural integrity of subunits III and Vila, thereby highlighting an indispensable nature of lipid-protein interactions in enzyme function such as proton uptake and oxygen channeling. Our results demonstrate the strength of molecular simulations in providing direct atomic description of lipid-protein processes that are difficult to achieve experimentally.
  • Miettinen, Helena E.; Rono, Kristiina; Koivusalo, Saila B.; Eriksson, Johan G.; Gylling, Helena (2018)
    Background and aims: Impaired glucose metabolism during pregnancy may associate with changes in fetal cholesterol metabolism. We investigated if gestational diabetes mellitus (GDM) affects newborn cholesterol metabolism as determined by cord blood squalene and non-cholesterol sterols. Furthermore, we examined potential correlations between cord blood and maternal serum non-cholesterol sterols. Methods: Pregnant women at risk for GDM (BMI>30 kg/m(2)) were enrolled from maternity clinics in Finland. GDM was determined from the results of an oral glucose tolerance test. Serum samples were taken in the third trimester of pregnancy, and cord blood samples collected from their newborns at birth. Squalene and non-cholesterol sterols were analyzed from serum and cord blood by gas liquid chromatography. All women with GDM were in good glycaemic control. Results: The ratios of squalene and non-cholesterol sterols to cholesterol (100 x mu mol/mmol of cholesterol) in cord blood did not differ between the infants born to mothers with GDM (n = 15) or mothers with normal glucose tolerance (n = 13). The ratios of sitosterol and campesterol to cholesterol in the cord blood correlated with the corresponding maternal serum ratios (r = 0.70, p <0.0001) in both groups. Conclusions: In obese women under good glycaemic control, GDM did not affect newborn cholesterol metabolism. Cord blood sitosterol and campesterol ratios to cholesterol correlated with the corresponding maternal serum ratios thus potentially reflecting maternal-fetal cholesterol transport. (C) 2018 Elsevier B.V. All rights reserved.
  • Verkasalo, Erkki; Roitto, Marja; Möttönen, Veikko; Ilvesniemi, Hannu (2022)
    The aim of the study was to quantify total extractive contents and lipophilic compounds, stilbenes, and lignans in Scots pine stem wood, stem bark, branch biomass, and sawmill residues in four climatic regions of Finland to evaluate the most optimal sources of extractives for bio-based chemical biorefining and bioenergy products. Data were derived from 78 chip samples from the before-mentioned raw materials, the samples being pooled by tree height position from the sample trees of 42 experimental forest stands, and sawdust lots from 10 log stands. Accelerated solvent extraction (ASE) was employed to determine total extractive contents, followed by gas chromatography with flame ionization detection (GC-FID) to quantify extractive groups and gas chromatography-mass spectrometry (GC-MS) to analyse individual extractive compounds. Resin acids and triglycerides followed by fatty acids were the dominant extractive groups. Resin acids were most abundant in stem wood from final fellings and in sawdust, fatty acids in bark and branch biomass, and triglycerides also in stem wood from thinnings and the top parts of trees. Of the minor extractive groups, stilbenes were the most abundant in stem wood from final fellings and in sawdust, and steryl esters, sterols, and lignans in bark and branch biomass, the two last groups almost missing from other biomass components. Regional differences in the contents of extractive groups were generally small, 1.0-1.5 percentage points at the maximum, but factor analysis distinguished northern and southern regions into their own groups. Bark was the most potential source of fatty acids and sterols in southern Finland, and triglycerides and steryl esters in northern Finland. In stem wood, steryl esters, triglycerides, and lignans decreased and stilbenes increased from north to south. Certain fatty acids and resin acids were more frequent in the north. The results highlighted the importance of focused procurement and efficient sorting of raw materials, purity, unique properties, and feasible isolation techniques for competitive ability as well as large raw material volumes or well-defined value-added products.
  • Keinanen, Marja; Kakela, Reijo; Ritvanen, Tiina; Myllyla, Timo; Ponni, Jukka; Vuorinen, Pekka J. (2017)
    Sprat (Sprattus sprattus) and small herring (Clupea harengus) are the dominant prey fish of Atlantic salmon (Salmo salar) in the Baltic Sea. If the fatty acid (FA) proportions of sprat and herring differ, the dietary history of ascending salmon could be determined from their FA profiles. Therefore, we investigated the FA composition of several age groups of whole sprat and small herring, caught from the three main feeding areas of salmon in autumn and spring. Oleic acid (18: 1n-9) was the most prevalent FA in sprat and characteristic of this species. In herring, palmitic acid (16: 0) was the most common FA, but herring lipid was characterized by n-6 polyunsaturated FAs, and moreover, by palmitoleic acid (16: 1n-7) and vaccenic acid (18: 1n-7). Due to the higher lipid content of sprat, the concentrations of all other FAs, excluding these, were higher in sprat than in herring. The concentration of docosahexaenoic acid (DHA, 22: 6n-3) increased with an increase in the lipid content and was consequently highest in the youngest specimens, being in young sprat almost double that of young herring, and 2.6 times higher in the sprat biomass than in that of herring. As a result of a decrease in the DHA concentration with age, the ratio thiamine/DHA increased with respect to age in both species, and was lower in sprat than in herring. It is concluded that an abundance of DHA in the diet of salmon most likely increases oxidative stress because of the susceptibility of DHA to peroxidation, and thus decreases thiamine resources of fasting, prespawning salmon. Because the FA composition of sprat and herring differs, and the relative abundancies of prey fish differ between the feeding areas of salmon, the feeding area of ascending salmon can most probably be derived by comparing their FA profiles.
  • Lempiäinen, Juha; Ijäs, Petra; Niiranen, Teemu J.; Kaste, Markku; Karhunen, Pekka J.; Lindsberg, Perttu J.; Erkinjuntti, Timo; Melkas, Susanna (2020)
    Haptoglobin (Hp) is a plasma protein that binds free hemoglobin and protects tissues from oxidative damage. An Hp2 allele has been associated with an increased risk of cardiovascular complications. On the other hand, recent studies have suggested that Hp1 allele increases risk to develop severe cerebral small vessel disease. We aimed to replicate this finding in a first-ever stroke patient cohort. Hp was genotyped by PCR and gel electrophoresis in the Helsinki Stroke Aging Memory Study in patients with DNA and magnetic resonance imaging (MRI) available (SAM; n = 316). Lacunar infarcts and white matter lesions (WML) classified by Fazekas grading from brain MRI were associated with Hp genotypes. As population controls, we used participants of Cardiovascular diseases-a sub study of Health 2000 Survey (n = 1417). In the SAM cohort, 63.0% of Hp1-1 carriers (n = 46), 52.5% of Hp1-2 carriers (n = 141) and 51.2% of Hp2-2 carriers (n = 129) had severe WML (p = 0.372). There was no difference in severe WMLs between Hp1-1 vs. Hp1-2 and Hp2-2 carriers (p = 0.201). In addition, 68.9% of Hp1-1 carriers (n = 45), 58.5% of Hp1-2 carriers (n = 135), and 61.8% of Hp2-2 carriers (n = 126) had one or more lacunar lesions (p = 0.472). There was no difference in the number of patients with at least one lacunar infarct between Hp1-1 vs. Hp1-2 and Hp2-2 groups (p = 0.322). Neither was there any difference when diabetic patients (type I and II) were examined separately. Hp1 allele is not associated with an increased risk for cerebral small vessel disease in a well-characterized Finnish stroke patient cohort.
  • Rosa-Sibakov, Natalia; Mäkelä, Noora; Aura, Anna-Marja; Sontag-Strohm, Tuula; Nordlund, Emilia (2020)
    The objective of this work was to evaluate the role of beta-glucan molecular weight (M-w) and the presence of other carbohydrates on the physiological functionality of oat branviaanin vitrodigestion study. A complete approach using three differentin vitrodigestion models (viscosity of the small intestine digest, reduction of bile acids and on-line measurement of gas evolution) was used to predict the physiological functionality of enzymatically modified oat bran concentrate (OBC). OBC was enzymatically treated with two beta-glucanase preparations at three different levels in order to specifically decrease beta-glucanM(w)(Pure: purified beta-glucanase) or beta-glucan and other cell wall polysaccharides (Mix: commercial food-grade cell wall degrading enzyme preparation). TheM(w)of beta-glucan in OBC was tailored to high (1000 kDa), medium (200-500 kDa) and low (
  • Zini, Jacopo; Saari, Heikki; Ciana, Paolo; Viitala, Tapani; Lohmus, Andres; Saarinen, Jukka; Yliperttula, Marjo (2022)
    Extracellular vesicles (EVs) are a complex and heterogeneous population of nanoparticles involved in cell-to-cell communication. Recently, numerous studies have indicated the potential of EVs as therapeutic agents, drug carriers and diagnostic tools. However, the results of these studies are often difficult to evaluate, since different characterization methods are used to assess the purity, physical and biochemical characteristics of the EV samples. In this study, we compared four methods for the EV sample characterization and purity assessment: i) the particle-to-protein ratio based on particle analyses with nanoparticle tracking and protein concentration by bicinchoninic acid assay, ii) Western Blot analysis for specific EV biomarkers, iii) two spectroscopic lipid-to protein ratios by either the attenuated total reflection Fourier transform infrared (ATR-FTIR) or Raman spectroscopy. The results confirm the value of Raman and ATR-FTIR spectroscopy as robust, fast and operator independent tools that require only a few microliters of EV sample. We propose that the spectroscopic lipid-to protein (Li/Pr) ratios are reliable parameters for the purity assessment of EV preparations. Moreover, apart from determining protein concentrations, we show that ATR-FTIR spectroscopy can also be used for indirect measurements of EV concentrations. Nevertheless, the Li/Pr ratios do not represent full characterization of the EV preparations. For a complete characterization of selected EV preparations, we recommend also additional use of particle size distribution and EV biomarker analysis.
  • Setala, Niko L.; Holopainen, Juha M.; Metso, Jari; Yohannes, Gebrenegus; Hiidenhovi, Jaakko; Andersson, Leif C.; Eriksson, Ove; Robciuc, Alexandra; Jauhiainen, Matti (2010)
  • Herrala, Maria; Turunen, Soile; Hanhineva, Kati; Lehtonen, Marko; Mikkonen, Jopi J. W.; Seitsalo, Hubertus; Lappalainen, Reijo; Tjäderhane, Leo; Niemelä, Raija K.; Salo, Tuula; Myllymaa, Sami; Kullaa, Arja M.; Kärkkäinen, Olli (2021)
    Saliva is a complex oral fluid, and plays a major role in oral health. Primary Sjogren's syndrome (pSS), as an autoimmune disease that typically causes hyposalivation. In the present study, salivary metabolites were studied from stimulated saliva samples (n = 15) of female patients with pSS in a group treated with low-dose doxycycline (LDD), saliva samples (n = 10) of non-treated female patients with pSS, and saliva samples (n = 14) of healthy age-matched females as controls. Saliva samples were analyzed with liquid chromatography mass spectrometry (LC-MS) based on the non-targeted metabolomics method. The saliva metabolite profile differed between pSS patients and the healthy control (HC). In the pSS patients, the LDD treatment normalized saliva levels of several metabolites, including tyrosine glutamine dipeptide, phenylalanine isoleucine dipeptide, valine leucine dipeptide, phenylalanine, pantothenic acid (vitamin B5), urocanic acid, and salivary lipid cholesteryl palmitic acid (CE 16:0), to levels seen in the saliva samples of the HC. In conclusion, the data showed that pSS is associated with an altered saliva metabolite profile compared to the HC and that the LLD treatment normalized levels of several metabolites associated with dysbiosis of oral microbiota in pSS patients. The role of the saliva metabolome in pSS pathology needs to be further studied to clarify if saliva metabolite levels can be used to predict or monitor the progress and treatment of pSS.
  • Palviainen, Mari; Saari, Heikki; Kärkkäinen, Olli; Pekkinen, Jenna; Auriola, Seppo; Yliperttula, Marjo; Puhka, Maija; Hanhineva, Kati; Siljander, Pia R-M (2019)
    One of the greatest bottlenecks in extracellular vesicle (EV) research is the production of sufficient material in a consistent and effective way using in vitro cell models. Although the production of EVs in bioreactors maximizes EV yield in comparison to conventional cell cultures, the impact of their cell growth conditions on EVs has not yet been established. In this study, we grew two prostate cancer cell lines, PC-3 and VCaP, in conventional cell culture dishes and in two-chamber bioreactors to elucidate how the growth environment affects the EV characteristics. Specifically, we wanted to investigate the growth condition-dependent differences by non-targeted metabolite profiling using liquid chromatography-mass spectrometry (LC-MS) analysis. EVs were also characterized by their morphology, size distribution, and EV protein marker expression, and the EV yields were quantified by NTA. The use of bioreactor increased the EV yield >100 times compared to the conventional cell culture system. Regarding morphology, size distribution and surface markers, only minor differences were observed between the bioreactor-derived EVs (BR-EVs) and the EVs obtained from cells grown in conventional cell cultures (C-EVs). In contrast, metabolomic analysis revealed statistically significant differences in both polar and non-polar metabolites when the BR-EVs were compared to the C-EVs. The results show that the growth conditions markedly affected the EV metabolite profiles and that metabolomics was a sensitive tool to study molecular differences of EVs. We conclude that the cell culture conditions of EV production should be standardized and carefully detailed in publications and care should be taken when EVs from different production platforms are compared with each other for systemic effects.
  • Tikkanen, Emmi; Minicocci, Ilenia; Hällfors, Jenni; Di Costanzo, Alessia; D'Erasmo, Laura; Poggiogalle, Eleonora; Donini, Lorenzo Maria; Wurtz, Peter; Jauhiainen, Matti; Olkkonen, Vesa M.; Arca, Marcello (2019)
    Objective- Loss-of-function (LOF) variants in the ANGPTL3 (angiopoietin-like protein 3) have been associated with low levels of plasma lipoproteins and decreased coronary artery disease risk. We aimed to determine detailed metabolic effects of genetically induced ANGPTL3 deficiency in fasting and postprandial state. Approach and Results- We studied individuals carrying S17X LOF mutation in ANGPTL3 (6 homozygous and 32 heterozygous carriers) and 38 noncarriers. Nuclear magnetic resonance metabolomics was used to quantify 225 circulating metabolic measures. We compared metabolic differences between LOF carriers and noncarriers in fasting state and after a high-fat meal. In fasting, ANGPTL3 deficiency was characterized by similar extent of reductions in LDL (low-density lipoprotein) cholesterol (0.74 SD units lower concentration per LOF allele [95% CI, 0.42-1.06]) as observed for many TRL (triglyceride-rich lipoprotein) measures, including VLDL (very-low-density lipoprotein) cholesterol (0.75 [95% CI, 0.45-1.05]). Within most lipoprotein subclasses, absolute levels of cholesterol were decreased more than triglycerides, resulting in the relative proportion of cholesterol being reduced within TRLs and their remnants. Further, beta-hydroxybutyrate was elevated (0.55 [95% CI, 0.21-0.89]). Homozygous ANGPTL3 LOF carriers showed essentially no postprandial increase in TRLs and fatty acids, without evidence for adverse compensatory metabolic effects. Conclusions- In addition to overall triglyceride- and LDL cholesterol-lowering effects, ANGPTL3 deficiency results in reduction of cholesterol proportion within TRLs and their remnants. Further, ANGPTL3 LOF carriers had elevated ketone body production, suggesting enhanced hepatic fatty acid beta-oxidation. The detailed metabolic profile in human knockouts of ANGPTL3 reinforces inactivation of ANGPTL3 as a promising therapeutic target for decreasing cardiovascular risk.
  • Hallamaa, Raija; Batchu, Krishna (2016)
    Background: Lipids have become an important target for searching new biomarkers typical of different autoimmune and allergic diseases. The most common allergic dermatitis of the horse is related to stings of insects and is known as insect bite hypersensitivity (IBH) or summer eczema, referring to its recurrence during the summer months. This intense pruritus has certain similarities with atopic dermatitis of humans. The treatment of IBH is difficult and therefore new strategies for therapy are needed. Autoserum therapy based on the use of serum phospholipids has recently been introduced for horses. So far, serum lipids relating to these allergic disorders have been poorly determined. The main aim of this study was to analyse phospholipid profiles in the sera of horses with allergic dermatitis and in their healthy controls and to further assess whether these lipid profiles change according to the clinical status after therapy. Methods: Sera were collected from 10 horses with allergic dermatitis and from 10 matched healthy controls both before and 4 weeks after the therapy of the affected horses. Eczema horses were treated with an autogenous preparation made from a horse's own serum and used for oral medication. Samples were analysed for their phospholipid content by liquid chromatography coupled to a triple-quadrupole mass spectrometer (LC-MS). Data of phospholipid concentrations between the groups and over the time were analysed by using the Friedman test. Correlations between the change of concentrations and the clinical status were assessed by Spearman's rank correlation test. Results: The major phospholipid classes detected were phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylinositol (PI) and phosphatidylethanolamine (PE). Eczema horses had significantly lower total concentrations of PC (p <0.0001) and SM (p = 0.0115) than their healthy controls. After a 4-week therapy, no significant differences were found between the groups. Changes in SM concentrations correlated significantly with alterations in clinical signs (p = 0.0047). Conclusions: Horses with allergic dermatitis have an altered phospholipid profile in their sera as compared with healthy horses and these profiles seem to change according to their clinical status. Sphingomyelin seems to have an active role in the course of equine insect bite hypersensitivity.
  • Mir, Sartaj Ahmad; Chen, Li; Burugupalli, Satvika; Burla, Bo; Ji, Shanshan; Smith, Adam Alexander T.; Narasimhan, Kothandaraman; Ramasamy, Adaikalavan; Tan, Karen Mei Ling; Huynh, Kevin; Giles, Corey; Mei, Ding; Wong, Gerard; Yap, Fabian; Tan, Kok Hian; Collier, Fiona; Saffery, Richard; Vuillermin, Peter; Bendt, Anne K.; Burgner, David; Ponsonby, Anne Louise; Lee, Yung Seng; Chong, Yap Seng; Gluckman, Peter D.; Eriksson, Johan G.; Meikle, Peter J.; Wenk, Markus R.; Karnani, Neerja (2022)
    Background: Lipids play a vital role in health and disease, but changes to their circulating levels and the link with obesity remain poorly characterized in expecting mothers and their offspring in early childhood. Methods: LC-MS/MS-based quantitation of 480 lipid species was performed on 2491 plasma samples collected at 4 time points in the mother-offspring Asian cohort GUSTO (Growing Up in Singapore Towards healthy Outcomes). These 4 time points constituted samples collected from mothers at 26–28 weeks of gestation (n=752) and 4–5 years postpartum (n=650), and their offspring at birth (n=751) and 6 years of age (n=338). Linear regression models were used to identify the pregnancy and developmental age-specific variations in the plasma lipidomic profiles, and their association with obesity risk. An independent birth cohort (n=1935), the Barwon Infant Study (BIS), comprising mother-offspring dyads of Caucasian origin was used for validation. Results: Levels of 36% of the profiled lipids were significantly higher (absolute fold change > 1.5 and Padj < 0.05) in antenatal maternal circulation as compared to the postnatal phase, with phosphatidylethanolamine levels changing the most. Compared to antenatal maternal lipids, cord blood showed lower concentrations of most lipid species (79%) except lysophospholipids and acylcarnitines. Changes in lipid concentrations from birth to 6 years of age were much higher in magnitude (log2FC=−2.10 to 6.25) than the changes observed between a 6-year-old child and an adult (postnatal mother) (log2FC=−0.68 to 1.18). Associations of cord blood lipidomic profiles with birth weight displayed distinct trends compared to the lipidomic profiles associated with child BMI at 6 years. Comparison of the results between the child and adult BMI identified similarities in association with consistent trends (R2=0.75). However, large number of lipids were associated with BMI in adults (67%) compared to the children (29%). Pre-pregnancy BMI was specifically associated with decrease in the levels of phospholipids, sphingomyelin, and several triacylglycerol species in pregnancy. Conclusions: In summary, our study provides a detailed landscape of the in utero lipid environment provided by the gestating mother to the growing fetus, and the magnitude of changes in plasma lipidomic profiles from birth to early childhood. We identified the effects of adiposity on the circulating lipid levels in pregnant and non-pregnant women as well as offspring at birth and at 6 years of age. Additionally, the pediatric vs maternal overlap of the circulating lipid phenotype of obesity risk provides intergenerational insights and early opportunities to track and intervene the onset of metabolic adversities. Clinical trial registration: This birth cohort is a prospective observational study, which was registered on 1 July 2010 under the identifier NCT01174875.
  • Taddei, Cristina; Zhou, Bin; Bixby, Honor; Carrillo-Larco, Rodrigo M.; Danaei, Goodarz; Jackson, Rod T.; Farzadfar, Farshad; Sophiea, Marisa K.; Di Cesare, Mariachiara; Iurilli, Maria Laura Caminia; Martinez, Andrea Rodriguez; Asghari, Golaleh; Dhana, Klodian; Gulayin, Pablo; Kakarmath, Sujay; Santero, Marilina; Voortman, Trudy; Riley, Leanne M.; Cowan, Melanie J.; Savin, Stefan; Bennett, James E.; Stevens, Gretchen A.; Paciorek, Christopher J.; Aekplakorn, Wichai; Cifkova, Renata; Giampaoli, Simona; Kengne, Andre Pascal; Khang, Young-Ho; Kuulasmaa, Kari; Laxmaiah, Avula; Margozzini, Paula; Mathur, Prashant; Nordestgaard, Borge G.; Zhao, Dong; Aadahl, Mette; Abarca-Gomez, Leandra; Rahim, Hanan Abdul; Abu-Rmeileh, Niveen M.; Acosta-Cazares, Benjamin; Adams, Robert J.; Agdeppa, Imelda A.; Aghazadeh-Attari, Javad; Aguilar-Salinas, Carlos A.; Agyemang, Charles; Ahluwalia, Tarunveer S.; Ahmad, Noor Ani; Ahmadi, Ali; Ahmadi, Naser; Ahmed, Soheir H.; Ahrens, Wolfgang; Ajlouni, Kamel; Alarouj, Monira; AlBuhairan, Fadia; AlDhukair, Shahla; Ali, Mohamed M.; Alkandari, Abdullah; Alkerwi, Ala'a; Aly, Eman; Amarapurkar, Deepak N.; Amouyel, Philippe; Andersen, Lars Bo; Anderssen, Sigmund A.; Anjana, Ranjit Mohan; Ansari-Moghaddam, Alireza; Aounallah-Skhiri, Hajer; Araujo, Joana; Ariansen, Inger; Aris, Tahir; Arku, Raphael E.; Arlappa, Nimmathota; Aryal, Krishna K.; Aspelund, Thor; Assuncao, Maria Cecilia F.; Auvinen, Juha; Avdicova, Maria; Azevedo, Ana; Azizi, Fereidoun; Azmin, Mehrdad; Balakrishna, Nagalla; Bamoshmoosh, Mohamed; Banach, Maciej; Bandosz, Piotr; Banegas, Jose R.; Barbagallo, Carlo M.; Barcelo, Alberto; Barkat, Amina; Bata, Iqbal; Batieha, Anwar M.; Batyrbek, Assembekov; Baur, Louise A.; Beaglehole, Robert; Belavendra, Antonisamy; Ben Romdhane, Habiba; Benet, Mikhail; Benn, Marianne; Berkinbayev, Salim; Bernabe-Ortiz, Antonio; Bernotiene, Gailute; Bettiol, Heloisa; Bhargava, Santosh K.; Bi, Yufang; Bienek, Asako; Bikbov, Mukharram; Bista, Bihungum; Bjerregaard, Peter; Bjertness, Espen; Bjertness, Marius B.; Bjorkelund, Cecilia; Bloch, Katia; Blokstra, Anneke; Bo, Simona; Boehm, Bernhard O.; Boggia, Jose G.; Boissonnet, Carlos P.; Bonaccio, Marialaura; Bongard, Vanina; Borchini, Rossana; Borghs, Herman; Bovet, Pascal; Brajkovich, Imperia; Breckenkamp, Juergen; Brenner, Hermann; Brewster, Lizzy M.; Bruno, Graziella; Bugge, Anna; Busch, Markus A.; de Leon, Antonio Cabrera; Cacciottolo, Joseph; Can, Gunay; Candido, Ana Paula C.; Capanzana, Mario; Capuano, Eduardo; Capuano, Vincenzo; Cardoso, Viviane C.; Carvalho, Joana; Casanueva, Felipe F.; Censi, Laura; Chadjigeorgiou, Charalambos A.; Chamukuttan, Snehalatha; Chaturvedi, Nish; Chen, Chien-Jen; Chen, Fangfang; Chen, Shuohua; Cheng, Ching-Yu; Cheraghian, Bahman; Chetrit, Angela; Chiou, Shu-Ti; Chirlaque, Maria-Dolores; Cho, Belong; Cho, Yumi; Chudek, Jerzy; Claessens, Frank; Clarke, Janine; Clays, Els; Concin, Hans; Confortin, Susana C.; Cooper, Cyrus; Costanzo, Simona; Cottel, Dominique; Cowell, Chris; Crujeiras, Ana B.; Csilla, Semanova; Cui, Liufu; Cureau, Felipe; D'Arrigo, Graziella; d'Orsi, Eleonora; Dallongeville, Jean; Damasceno, Albertino; Dankner, Rachel; Dantoft, Thomas M.; Dauchet, Luc; Davletov, Kairat; De Backer, Guy; De Bacquer, Dirk; de Gaetano, Giovanni; De Henauw, Stefaan; de Oliveira, Paula Duarte; De Ridder, David; De Smedt, Delphine; Deepa, Mohan; Deev, Alexander D.; Dehghan, Abbas; Delisle, Helene; Dennison, Elaine; Deschamps, Valerie; Dhimal, Meghnath; Di Castelnuovo, Augusto F.; Dika, Zivka; Djalalinia, Shirin; Dobson, Annette J.; Donfrancesco, Chiara; Donoso, Silvana P.; Doring, Angela; Dorobantu, Maria; Dragano, Nico; Drygas, Wojciech; Du, Yong; Duante, Charmaine A.; Duda, Rosemary B.; Dzerve, Vilnis; Dziankowska-Zaborszczyk, Elzbieta; Eddie, Ricky; Eftekhar, Ebrahim; Eggertsen, Robert; Eghtesad, Sareh; Eiben, Gabriele; Ekelund, Ulf; El Ati, Jalila; Eldemire-Shearer, Denise; Eliasen, Marie; Elosua, Roberto; Erasmus, Rajiv T.; Erbel, Raimund; Erem, Cihangir; Eriksen, Louise; Eriksson, Johan G.; Escobedo-de la Pena, Jorge; Eslami, Saeid; Esmaeili, Ali; Evans, Alun; Faeh, David; Fall, Caroline H.; Faramarzi, Elnaz; Farjam, Mojtaba; Fattahi, Mohammad Reza; Felix-Redondo, Francisco J.; Ferguson, Trevor S.; Fernandez-Berges, Daniel; Ferrante, Daniel; Ferrari, Marika; Ferreccio, Catterina; Ferrieres, Jean; Foger, Bernhard; Foo, Leng Huat; Forslund, Ann-Sofie; Forsner, Maria; Fouad, Heba M.; Francis, Damian K.; Franco, Maria do Carmo; Franco, Oscar H.; Frontera, Guillermo; Fujita, Yuki; Fumihiko, Matsuda; Furusawa, Takuro; Gaciong, Zbigniew; Galvano, Fabio; Gao, Jingli; Garcia-de-la-Hera, Manoli; Garnett, Sarah P.; Gaspoz, Jean-Michel; Gasull, Magda; Gazzinelli, Andrea; Geleijnse, Johanna M.; Ghanbari, Ali; Ghasemi, Erfan; Gheorghe-Fronea, Oana-Florentina; Ghimire, Anup; Gianfagna, Francesco; Gill, Tiffany K.; Giovannelli, Jonathan; Gironella, Glen; Giwercman, Aleksander; Goltzman, David; Goncalves, Helen; Gonzalez-Chica, David A.; Gonzalez-Gross, Marcela; Gonzalez-Rivas, Juan P.; Gonzalez-Villalpando, Clicerio; Gonzalez-Villalpando, Maria-Elena; Gonzalez, Angel R.; Gottrand, Frederic; Graff-Iversen, Sidsel; Gregor, Ronald D.; Grodzicki, Tomasz; Grontved, Anders; Grosso, Giuseppe; Gruden, Gabriella; Gu, Dongfeng; Guallar-Castillon, Pilar; Guan, Ong Peng; Gudmundsson, Elias F.; Gudnason, Vilmundur; Guerrero, Ramiro; Guessous, Idris; Gunnlaugsdottir, Johanna; Gupta, Rajeev; Gutierrez, Laura; Gutzwiller, Felix; Ha, Seongjun; Hadaegh, Farzad; Haghshenas, Rosa; Hakimi, Hamid; Hambleton, Ian R.; Hamzeh, Behrooz; Hantunen, Sari; Kumar, Rachakulla Hari; Hashemi-Shahri, Seyed Mohammad; Hata, Jun; Haugsgjerd, Teresa; Hayes, Alison J.; He, Jiang; He, Yuna; Hendriks, Marleen Elisabeth; Henriques, Ana; Herrala, Sauli; Heshmat, Ramin; Hill, Allan G.; Ho, Sai Yin; Ho, Suzanne C.; Hobbs, Michael; Hofman, Albert; Homayounfar, Reza; Hopman, Wilma M.; Horimoto, Andrea R. V. R.; Hormiga, Claudia M.; Horta, Bernardo L.; Houti, Leila; Howitt, Christina; Htay, Thein Thein; Htet, Aung Soe; Htike, Maung Maung Than; Huerta, Jose Maria; Huhtaniemi, Ilpo Tapani; Huisman, Martijn; Hunsberger, Monica L.; Husseini, Abdullatif S.; Huybrechts, Inge; Hwalla, Nahla; Iacoviello, Licia; Iannone, Anna G.; Ibrahim, Mohsen M.; Wong, Norazizah Ibrahim; Iglesia, Iris; Ikeda, Nayu; Ikram, M. Arfan; Iotova, Violeta; Irazola, Vilma E.; Ishida, Takafumi; Islam, Muhammad; Ismail, Aziz Al-Safi; Iwasaki, Masanori; Jacobs, Jeremy M.; Jaddou, Hashem Y.; Jafar, Tazeen; James, Kenneth; Jamrozik, Konrad; Janszky, Imre; Janus, Edward; Jarvelin, Marjo-Riitta; Jasienska, Grazyna; Jelakovic, Ana; Jelakovic, Bojan; Jennings, Garry; Jensen, Gorm B.; Jeong, Seung-lyeal; Jha, Anjani Kumar; Jiang, Chao Qiang; Jimenez, Ramon O.; Jockel, Karl-Heinz; Joffres, Michel; Jokelainen, Jari J.; Jonas, Jost B.; Jorgensen, Torben; Joshi, Pradeep; Joukar, Farahnaz; Jozwiak, Jacek; Juolevi, Anne; Kafatos, Anthony; Kajantie, Eero O.; Kalter-Leibovici, Ofra; Kamaruddin, Nor Azmi; Kamstrup, Pia R.; Karki, Khem B.; Katz, Joanne; Kauhanen, Jussi; Kaur, Prabhdeep; Kavousi, Maryam; Kazakbaeva, Gyulli; Keil, Ulrich; Keinanen-Kiukaanniemi, Sirkka; Kelishadi, Roya; Keramati, Maryam; Kerimkulova, Alina; Kersting, Mathilde; Khader, Yousef Saleh; Khalili, Davood; Khateeb, Mohammad; Kheradmand, Motahareh; Khosravi, Alireza; Kiechl-Kohlendorfer, Ursula; Kiechl, Stefan; Killewo, Japhet; Kim, Hyeon Chang; Kim, Jeongseon; Kim, Yeon-Yong; Klumbiene, Jurate; Knoflach, Michael; Ko, Stephanie; Kohler, Hans-Peter; Kohler, Iliana; Kolle, Elin; Kolsteren, Patrick; Konig, Jurgen; Korpelainen, Raija; PaulKorrovits; Kos, Jelena; Koskinen, Seppo; Kouda, Katsuyasu; Kowlessur, Sudhir; Kratzer, Wolfgang; Kriemler, Susi; Kristensen, Peter Lund; Krokstad, Steiner; Kromhout, Daan; Kujala, Urho M.; Kurjata, Pawel; Kyobutungi, Catherine; Laamiri, Fatima Zahra; Laatikainen, Tiina; Lachat, Carl; Laid, Youcef; Lam, Tai Hing; Lambrinou, Christina-Paulina; Lanska, Vera; Lappas, Georg; Larijani, Bagher; Latt, Tint Swe; Laugsand, Lars E.; Lazo-Porras, Maria; Lee, Jeannette; Lee, Jeonghee; Lehmann, Nils; Lehtimaki, Terho; Levitt, Naomi S.; Li, Yanping; Lilly, Christa L.; Lim, Wei-Yen; Lima-Costa, M. Fernanda; Lin, Hsien-Ho; Lin, Xu; Lin, Yi-Ting; Lind, Lars; Linneberg, Allan; Lissner, Lauren; Liu, Jing; Loit, Helle-Mai; Lopez-Garcia, Esther; Lopez, Tania; Lotufo, Paulo A.; Lozano, Jose Eugenio; Luksiene, Dalia; Lundqvist, Annamari; Lundqvist, Robert; Lunet, Nuno; Ma, Guansheng; Machado-Coelho, George L. L.; Machado-Rodrigues, Aristides M.; Machi, Suka; Madar, Ahmed A.; Maggi, Stefania; Magliano, Dianna J.; Magriplis, Emmanuella; Mahasampath, Gowri; Maire, Bernard; Makdisse, Marcia; Malekzadeh, Fatemeh; Reza Malekzadeh; Rao, Kodavanti Mallikharjuna; Manios, Yannis; Mann, Jim; Mansour-Ghanaei, Fariborz; Manzato, Enzo; Marques-Vidal, Pedro; Martorell, Reynaldo; Mascarenhas, Luis P.; Mathiesen, Ellisiv B.; Matsha, Tandi E.; Mavrogianni, Christina; McFarlane, Shelly R.; McGarvey, Stephen T.; McLachlan, Stela; McLean, Rachael M.; McLean, Scott B.; McNulty, Breige A.; Mediene-Benchekor, Sounnia; Mehdipour, Parinaz; Mehlig, Kirsten; Mehrparvar, AmirHoushang; Meirhaeghe, Aline; Meisinger, Christa; Menezes, Ana Maria B.; Menon, Geetha R.; Merat, Shahin; Mereke, Alibek; Meshram, Indrapal I.; Metcalf, Patricia; Meyer, Haakon E.; Mi, Jie; Michels, Nathalie; Miller, Jody C.; Minderico, Claudia S.; Mini, G. K.; Miquel, Juan Francisco; Miranda, J. Jaime; Mirjalili, Mohammad Reza; Mirrakhimov, Erkin; Modesti, Pietro A.; Moghaddam, Sahar Saeedi; Mohajer, Bahram; Mohamed, MostafaK; Mohammad, Kazem; Mohammadi, Zahra; Mohammadifard, Noushin; Mohammadpourhodki, Reza; Mohan, Viswanathan; Mohanna, Salim; MohdYusoff, Muhammad Fadhli; Mohebbi, Iraj; Mohebi, Farnam; Moitry, Marie; Mollehave, Line T.; Mller, Niels C.; Molnar, Denes; Momenan, Amirabbas; Mondo, Charles K.; Monterrubio-Flores, Eric; Moosazadeh, Mahmood; Morejon, Alain; Moreno, Luis A.; Morgan, Karen; Morin, Suzanne N.; Moschonis, George; Mossakowska, Malgorzata; Mostafa, Aya; Mota, Jorge; Motlagh, Mohammad Esmaeel; Motta, Jorge; Msyamboza, Kelias P.; Muiesan, Maria L.; Muller-Nurasyid, Martina; Mursu, Jaakko; Mustafa, Norlaila; Nabipour, Iraj; Naderimagham, Shohreh; Nagel, Gabriele; Naidu, Balkish M.; Najafi, Farid; Nakamura, Harunobu; Nang, Ei Ei K.; Nangia, Vinay B.; Nauck, Matthias; Neal, William A.; Nejatizadeh, Azim; Nenko, Ilona; Nervi, Flavio; Nguyen, Nguyen D.; Quang Ngoc Nguyen; Nieto-Martinez, Ramfis E.; Nihal, Thomas; Niiranen, Teemu J.; Ning, Guang; Ninomiya, Toshiharu; Noale, Marianna; Noboa, Oscar A.; Noto, Davide; Al Nsour, Mohannad; Nuhoglu, Irfan; O'Neill, Terence W.; O'Reilly, Dermot; Ochoa-Aviles, Angelica M.; Oh, Kyungwon; Ohtsuka, Ryutaro; Olafsson, Orn; Olie, Valerie; Oliveira, Isabel O.; Omar, Mohd Azahadi; Onat, Altan; Ong, SokKing; Ordunez, Pedro; Ornelas, Rui; Ortiz, Pedro J.; Osmond, Clive; Ostojic, Sergej M.; Ostovar, Afshin; Otero, Johanna A.; Owusu-Dabo, Ellis; Paccaud, Fred Michel; Pahomova, Elena; Pajak, Andrzej; Palmieri, Luigi; Pan, Wen-Harn; Panda-Jonas, Songhomitra; Panza, Francesco; Parnell, Winsome R.; Patel, Nikhil D.; Peer, Nasheeta; Peixoto, Sergio Viana; Peltonen, Markku; Pereira, Alexandre C.; Peters, Annette; Petersmann, Astrid; Petkeviciene, Janina; Peykari, Niloofar; Son Thai Pham; Pichardo, Rafael N.; Pigeot, Iris; Pilav, Aida; Pilotto, Lorenza; Piwonska, Aleksandra; Pizarro, Andreia N.; Plans-Rubio, Pedro; Plata, Silvia; Pohlabeln, Hermann; Porta, Miquel; Portegies, Marileen L. P.; Poudyal, Anil; Pourfarzi, Farhad; Poustchi, Hossein; Pradeepa, Rajendra; Price, Jacqueline F.; Providencia, Rui; Puder, Jardena J.; Puhakka, Soile E.; Punab, Margus; Qorbani, Mostafa; Tran Quoc Bao; Radisauskas, Ricardas; Rahimikazerooni, Salar; Raitakari, Olli; Rao, Sudha Ramachandra; Ramachandran, Ambady; Ramos, Elisabete; Ramos, Rafel; Rampal, Lekhraj; Rampal, Sanjay; Redon, Josep; Reganit, Paul Ferdinand M.; Revilla, Luis; Rezaianzadeh, Abbas; Ribeiro, Robespierre; Richter, Adrian; Rigo, Fernando; de Wit, Tobias F. Rinke; Rodriguez-Artalejo, Fernando; Rodriguez-Perez, Maria del Cristo; Rodriguez-Villamizar, Laura A.; Roggenbuck, Ulla; Rojas-Martinez, Rosalba; Romaguera, Dora; Romeo, Elisabetta L.; Rosengren, Annika; Roy, Joel G. R.; Rubinstein, Adolfo; Ruidavets, Jean-Bernard; Ruiz-Betancourt, Blanca Sandra; Russo, Paola; Rust, Petra; Rutkowski, Marcin; Sabanayagam, Charumathi; Sachdev, Harshpal S.; Sadjadi, Alireza; Safarpour, Ali Reza; Safiri, Saeid; Saidi, Olfa; Saki, Nader; Salanave, Benoit; Salmeron, Diego; Salomaa, Veikko; Salonen, Jukka T.; Salvetti, Massimo; Sanchez-Abanto, Jose; Sans, Susana; Santaliestra-Pasias, Alba M.; Santos, Diana A.; Santos, MariaPaula; Santos, Rute; Saramies, Jouko L.; Sardinha, Luis B.; Sarrafzadegan, Nizal; Saum, Kai-Uwe; Savva, Savvas C.; Sawada, Norie; Sbaraini, Mariana; Scazufca, Marcia; Schaan, Beatriz D.; Schargrodsky, Herman; Scheidt-Nave, Christa; Schienkiewitz, Anja; Schipf, Sabine; Schmidt, Carsten O.; Schottker, Ben; Schramm, Sara; Sebert, Sylvain; Sein, Aye Aye; Sen, Abhijit; Sepanlou, Sadaf G.; Servais, Jennifer; Shakeri, Ramin; Shalnova, Svetlana A.; Shamah-Levy, Teresa; Sharafkhah, Maryam; Sharma, Sanjib K.; Shaw, Jonathan E.; Shayanrad, Amaneh; Shi, Zumin; Shibuya, Kenji; Shimizu-Furusawa, Hana; Shin, Dong Wook; Shin, Youchan; Shirani, Majid; Shiri, Rahman; Shrestha, Namuna; Si-Ramlee, Khairil; Siani, Alfonso; Siantar, Rosalynn; Sibai, Abla M.; Santos Silva, Diego Augusto; Simon, Mary; Simons, Judith; Simons, Leon A.; Sjostrom, Michael; Skaaby, Tea; Slowikowska-Hilczer, Jolanta; Slusarczyk, Przemyslaw; Smeeth, Liam; Snijder, Marieke B.; Soderberg, Stefan; Soemantri, Agustinus; Sofat, Reecha; Solfrizzi, Vincenzo; Somi, Mohammad Hossein; Sonestedt, Emily; Sorensen, Thorkild I. A.; Jerome, Charles Sossa; Soumare, Aicha; Sozmen, Kaan; Sparrenberger, Karen; Staessen, Jan A.; Stathopoulou, Maria G.; Stavreski, Bill; Steene-Johannessen, Jostein; Stehle, Peter; Stein, Aryeh D.; Stessman, Jochanan; Stevanovic, Ranko; Stieber, Jutta; Stockl, Doris; Stokwiszewski, Jakub; Stronks, Karien; Strufaldi, Maria Wany; Suarez-Medina, Ramon; Sun, Chien-An; Sundstrom, Johan; Suriyawongpaisal, Paibul; Sy, Rody G.; Sylva, Rene Charles; Szklo, Moyses; Tai, E. Shyong; Tamosiunas, Abdonas; Tan, EngJoo; Tarawneh, Mohammed Rasoul; Tarqui-Mamani, Carolina B.; Taylor, Anne; Taylor, Julie; Tell, Grethe S.; Tello, Tania; Thankappan, K. R.; Thijs, Lutgarde; Thuesen, Betina H.; Toft, Ulla; Tolonen, Hanna K.; Tolstrup, Janne S.; Topbas, Murat; Topor-Madry, Roman; Tormo, Maria Jose; Tornaritis, Michael J.; Torrent, Maties; Torres-Collado, Laura; Traissac, Pierre; Trinh, Oanh T. H.; Truthmann, Julia; Tsugane, Shoichiro; Tulloch-Reid, Marshall K.; Tuomainen, Tomi-Pekka; Tuomilehto, Jaakko; Tybjaerg-Hansen, Anne; Tzourio, Christophe; Ueda, Peter; Ugel, Eunice; Ulmer, Hanno; Unal, Belgin; Uusitalo, Hannu M. T.; Valdivia, Gonzalo; Valvi, Damaskini; van Dam, RobM; van der Schouw, Yvonne T.; Van Herck, Koen; Hoang Van Minh; Rossem, Lenievan; Van Schoor, Natasja M.; van Valkengoed, Irene G. M.; Vanderschueren, Dirk; Vanuzzo, Diego; Varbo, Anette; Varona-Perez, Patricia; Vasan, Senthil K.; Vatten, Lars; Vega, Tomas; Veidebaum, Toomas; Velasquez-Melendez, Gustavo; Venero-Fernandez, Silvia J.; Veronesi, Giovanni; MoniqueVerschuren, W. M.; Victora, Cesar G.; Vidiawati, Dhanasari; Viet, Lucie; Villalpando, Salvador; Vioque, Jesus; Virtanen, Jyrki K.; Visvikis-Siest, Sophie; Viswanathan, Bharathi; Vlasoff, Tiina; Vollenweider, Peter; Voutilainen, Ari; Wade, Alisha N.; Wagner, Aline; Walton, Janette; Bebakar, Wan Mohamad Wan; WanMohamud, Wan Nazaimoon; Wang, Ming-Dong; Wang, Ningli; Wang, Qian; Wang, Ya Xing; Wang, Ying-Wei; Wannamethee, S. Goya; Wedderkopp, Niels; Wei, Wenbin; Whincup, Peter H.; Widhalm, Kurt; Widyahening, Indah S.; Wiecek, Andrzej; Wijga, Alet H.; Wilks, Rainford J.; Willeit, Johann; Willeit, Peter; Wilsgaard, Tom; Wojtyniak, Bogdan; Wong-McClure, Roy A.; Wong, Andrew; Wong, Tien Yin; Woo, Jean; Woodward, Mark; Wu, Frederick C.; Wu, Shouling; Xu, Haiquan; Xu, Liang; Yan, Weili; Yang, Xiaoguang; Yasuharu, Tabara; Ye, Xingwang; Yeow, Toh Peng; Yiallouros, Panayiotis K.; Yoosefi, Moein; Yoshihara, Akihiro; You, San-Lin; Younger-Coleman, Novie O.; Yusoff, Ahmad Faudzi; Zainuddin, Ahmad A.; Zakavi, Seyed Rasoul; Zali, Mohammad Reza; Zamani, Farhad; Zambon, Sabina; Zampelas, Antonis; KoZaw, Ko; Zdrojewski, Tomasz; Vrkic, Tajana Zeljkovic; Zhang, Zhen-Yu; Zhao, Wenhua; Zhen, Shiqi; Zheng, Yingfeng; Zholdin, Bekbolat; Zhussupov, Baurzhan; Zoghlami, Nada; Cisneros, Julio Zuniga; Gregg, Edward W.; Ezzati, Majid (2020)
    High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
  • Mäkelä, Noora; Rosa-Sibakov, Natalia; Wang, Yu-Jie; Mattila, Outi; Nordlund, Emilia; Sontag-Strohm, Tuula (2021)
    There is controversy about the role of viscosity and co-migrating molecules on the bile acid binding of betaglucan. Thus, this study aimed to investigate the impact of 8-glucan molecular weight and the content of both 8-glucan and phytate on the mobility of bile acids by modelling intestinal conditions in vitro. Two approaches were used to evaluate factors underlying this binding effect. The first studied bile acid binding capacity of soluble 8-glucan using purified compounds. Viscosity of the 8-glucan solution governed mainly the mobility of bile acid since both a decrease in 8-glucan concentration and degradation of 8-glucan by enzyme hydrolysis resulted in decreased binding. The second approach investigated the trapping of bile acids in the oat bran matrix. Results suggested trapping of bile acids by the 8-glucan gel network. Additionally, hydrolysis of phytate was shown to increase bile acid binding, probably due to better extractability of 8-glucan in this sample.
  • Walker, Hannah K.; Ottka, Claudia; Lohi, Hannes; Handel, Ian; Clements, Dylan N.; Gow, Adam G.; Mellanby, Richard J. (2022)
    Background Metabolic profiling identifies seasonal variance of serum metabolites in humans. Despite the presence of seasonal disease patterns, no studies have assessed whether serum metabolites vary seasonally in dogs. Hypothesis There is seasonal variation in the serum metabolite profiles of healthy dogs. Animals Eighteen healthy, client-owned dogs. Methods A prospective cohort study. Serum metabolomic profiles were assessed monthly in 18 healthy dogs over a 12-month period. Metabolic profiling was conducted using a canine-specific proton nuclear magnetic resonance spectroscopy platform, and the effects of seasonality were studied for 98 metabolites using a cosinor model. Seasonal component was calculated, which describes the seasonal variation of each metabolite. Results We found no evidence of seasonal variation in 93 of 98 metabolites. Six metabolites had statistically significant seasonal variance, including cholesterol (mean 249 mg/dL [6.47 mmol/L] with a seasonal component amplitude of 9 mg/dL [0.23 mmol/L]; 95% confidence interval [CI] 6-13 mg/dL [0.14-0.33 mmol/L], P < .008), with a peak concentration of 264 mg/dL (6.83 mmol/L) in June and trough concentration of 236 mg/dL (6.12 mmol/L) in December. In contrast, there was a significantly lower concentration of lactate (mean 20 mg/dL [2.27 mmol/L] with a seasonal component amplitude of 4 mg/dL [0.42 mmol/L]; 95% CI 2-6 mg/dL [0.22-0.62 mmol/L], P < .001) during the summer months compared to the winter months, with a peak concentration of 26 mg/dL (2.9 mmol/L) in February and trough concentration of 14 mg/dL (1.57 mmol/L) in July. Conclusions and Clinical Importance We found no clear evidence that seasonal reference ranges need to be established for serum metabolites of dogs.
  • Tajik, Behnam; Tuomainen, Tomi-Pekka; Isanejad, Masoud; Salonen, Jukka T.; Virtanen, Jyrki K. (2022)
    Purpose N-6 polyunsaturated fatty acids (PUFA), particularly linoleic acid (LA), have been associated with lower risk of coronary heart disease (CHD), but little is known about their antiarrhythmic properties. We investigated the association of the serum n-6 PUFAs with the risk of atrial fibrillation (AF), the most common type of cardiac arrhythmia. Methods The study included 2450 men from the Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years at baseline. The total n-6 PUFA includes linoleic acid (LA), arachidonic acid (AA), gamma-linolenic acid (GLA) and dihomo-gamma-linolenic acid (DGLA). Cox proportional hazards regression was used to estimate hazard ratio (HR) of incident events. Results During the mean follow-up of 22.4 years, 486 AF cases occurred. The multivariable-adjusted HR in the highest versus the lowest quartile of total serum n-6 PUFA concentration was 0.79 (95% CI 0.58-1.08, P trend = 0.04). When evaluated individually, only serum LA concentration was inversely associated with AF risk (multivariable-adjusted extreme-quartile HR 0.69, 95% CI 0.51-0.94, P trend = 0.02). These associations were stronger among the men without history of CHD or congestive heart failure at baseline, compared to men with such disease history (P for interaction = 0.05 for total n-6 PUFA and LA). Similar associations were observed with dietary LA and AA intakes. No significant associations were observed with serum AA, GLA or DGLA concentrations. Conclusions Higher circulating concentration and dietary intake of n-6 PUFA, mainly LA, are associated with lower risk of AF, especially among men without history of CHD or congestive heart failure.