Tapani Suortti

Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes

The risk determinants of type 1 diabetes, initiators of autoimmune response, mechanisms regulating progress toward β cell failure, and factors determining time of presentation of clinical diabetes are poorly understood. We investigated changes in the serum metabolome prospectively in children who later progressed to type 1 diabetes. Serum metabolite profiles were compared between sample series drawn from 56 children who progressed to type 1 diabetes and 73 controls who remained nondiabetic and permanently autoantibody negative. Individuals who developed diabetes had reduced serum levels of succinic acid and phosphatidylcholine (PC) at birth, reduced levels of triglycerides and antioxidant ether phospholipids throughout the follow up, and increased levels of proinflammatory lysoPCs several months before seroconversion to autoantibody positivity. The lipid changes were not attributable to HLA-associated genetic risk. The appearance of insulin and glutamic acid decarboxylase autoantibodies was preceded by diminished ketoleucine and elevated glutamic acid. The metabolic profile was partially normalized after the seroconversion. Autoimmunity may thus be a relatively late response to the early metabolic disturbances. Recognition of these preautoimmune alterations may aid in studies of disease pathogenesis and may open a time window for novel type 1 diabetes prevention strategies.

Global Transcript Profiles of Fat in Monozygotic Twins Discordant for BMI: Pathways behind Acquired Obesity

Background The acquired component of complex traits is difficult to dissect in humans. Obesity represents such a trait, in which the metabolic and molecular consequences emerge from complex interactions of genes and environment. With the substantial morbidity associated with obesity, a deeper understanding of the concurrent metabolic changes is of considerable importance. The goal of this study was to investigate this important acquired component and expose obesity-induced changes in biological pathways in an identical genetic background. Methods and Findings We used a special study design of “clonal controls,” rare monozygotic twins discordant for obesity identified through a national registry of 2,453 young, healthy twin pairs. A total of 14 pairs were studied (eight male, six female; white), with a mean ± standard deviation (SD) age 25.8 ± 1.4 y and a body mass index (BMI) difference 5.2 ± 1.8 kg/m2. Sequence analyses of mitochondrial DNA (mtDNA) in subcutaneous fat and peripheral leukocytes revealed no aberrant heteroplasmy between the co-twins. However, mtDNA copy number was reduced by 47% in the obese co-twins fat. In addition, novel pathway analyses of the adipose tissue transcription profiles exposed significant down-regulation of mitochondrial branched-chain amino acid (BCAA) catabolism (p < 0.0001). In line with this finding, serum levels of insulin secretion-enhancing BCAAs were increased in obese male co-twins (9% increase, p = 0.025). Lending clinical relevance to the findings, in both sexes the observed aberrations in mitochondrial amino acid metabolism pathways in fat correlated closely with liver fat accumulation, insulin resistance, and hyperinsulinemia, early aberrations of acquired obesity in these healthy young adults. Conclusions Our findings emphasize a substantial role of mitochondrial energy- and amino acid metabolism in obesity and development of insulin resistance.

Effect of enzymatic interesterification on the melting point of tallow-rapeseed oil (LEAR) mixture

To reduce the melting point of a tallow-rapeseed oil mixture, the triglyceride composition of the mixture was altered by enzymatic interesterification in a solvent-free system. The interesterification and hydrolysis were followed by melting point profiles and by free fatty acid determinations. The degree of hydrolysis was linearly related to the initial water content of the reaction mixture. The rate of the interesterification reaction was influenced by the amount of enzyme but not much by temperature between 50 and 70°C. The melting point reduction achieved by interesterification depended on the mass fractions of the substrates: the lower the mass fraction of tallow, the larger the reduction of the melting point.

Dietary carbohydrate modification alters serum metabolic profiles in individuals with the metabolic syndrome.

BACKGROUND AND AIMS Whole-grain cereals and diets with a low glycemic index may protect against the development of type 2 diabetes and heart disease, but the mechanisms are poorly understood. We studied the effect of carbohydrate modification on serum metabolic profiles, including lipids and branched chain amino acids, and dependencies between these and specific gene expression pathways in adipose tissue. METHODS AND RESULTS Twenty subjects with metabolic syndrome were selected from the larger FUNGENUT study population, randomized either to a diet high in oat and wheat bread and potato (OWP) or rye bread and pasta (RP). Serum metabolomics analyses were performed using ultra-performance liquid chromatography coupled to electrospray ionization mass spectrometry (UPLC/MS), gas chromatography (GC) and UPLC. In the OWP group multiple proinflammatory lysophosphatidylcholines increased, while in the RP group docosahexaenoic acid (DHA 22:6n-3) increased and isoleucine decreased. mRNA expression of stress reactions- and adipose tissue differentiation-related genes were up-regulated in adipose tissue in the OWP group. In the RP group, however, pathways related to stress reactions and insulin signaling and energy metabolism were down-regulated. The lipid profiles had the strongest association with the changes in the adipose tissue differentiation pathway when using the elastic net regression model of the lipidomic profiles on selected pathways. CONCLUSION Our results suggest that the dietary carbohydrate modification alters the serum metabolic profile, especially in lysoPC species, and may, thus, contribute to proinflammatory processes which in turn promote adverse changes in insulin and glucose metabolism.

Age- and Islet Autoimmunity–Associated Differences in Amino Acid and Lipid Metabolites in Children at Risk for Type 1 Diabetes

OBJECTIVE Islet autoimmunity precedes type 1 diabetes and often initiates in childhood. Phenotypic variation in islet autoimmunity relative to the age of its development suggests heterogeneous mechanisms of autoimmune activation. To support this notion, we examined whether serum metabolite profiles differ between children with respect to islet autoantibody status and the age of islet autoantibody development. RESEARCH DESIGN AND METHODS The study analyzed 29 metabolites of amino acid metabolism and 511 lipids assigned to 12 lipid clusters in children, with a type 1 diabetic parent, who first developed autoantibodies at age 2 years or younger (n = 13), at age 8 years or older (n = 22), or remained autoantibody-negative, and were matched for age, date of birth, and HLA genotypes (n = 35). Ultraperformance liquid chromatography and mass spectroscopy were used to measure metabolites and lipids quantitatively in the first autoantibody-positive and matched autoantibody-negative serum samples and in a second sample after 1 year of follow-up. RESULTS Differences in the metabolite profiles were observed relative to age and islet autoantibody status. Independent of age-related differences, autoantibody-positive children had higher levels of odd-chain triglycerides and polyunsaturated fatty acid–containing phospholipids than autoantibody-negative children and independent of age at first autoantibody appearance (P < 0.0001). Consistent with our hypothesis, children who developed autoantibodies by age 2 years had twofold lower concentration of methionine compared with those who developed autoantibodies in late childhood or remained autoantibody-negative (P < 0.0001). CONCLUSIONS Distinct metabolic profiles are associated with age and islet autoimmunity. Pathways that use methionine are potentially relevant for developing islet autoantibodies in early infancy.

Physical properties of (1→3),(1→4)-β-D-glucan preparates isolated from finnish oat varieties

Abstract The β-glucan content in the groats of different Finnish oat varieties cultivated in Finland varied from 3.2 to 5.3% and, in the fibre concentrates obtained by dry milling and a further concentration step including hot ethanol treatment and wet milling, from 11.8 to 18.3%. The viscosities of the isolated crude extracts varied widely between the varieties. Stil, Puhti, Yty and Nasta formed the most viscous solutions and Pol, the typical feed oat, the least viscous solution. The more significant differences in the viscosities between the oat varieties when measured at the same β-glucan concentration could be explained in terms of differences in mean molecular weight. Trypsin decreased the viscosity and the molecular weight of β-glucan of all samples. The viscosity of the β-glucan solutions was independent of pH both before or after enzyme treatment indicating that the protein or peptide is firmly bound to β-glucan.

Splanchnic balance of free fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic fatty liver disease.

BACKGROUND & AIMS Animal studies suggest that endocannabinoids could contribute to the development of nonalcoholic fatty liver disease (NAFLD). In addition, NAFLD has been shown to be associated with multiple changes in lipid concentrations in liver biopsies. There are no data on splanchnic free fatty acid (FFA), glycerol, ketone body, endocannabinoid, and lipid fluxes in vivo in subjects with NAFLD. METHODS We performed hepatic venous catheterization studies in combination with [(2)H(2)]palmitate infusion in the fasting state and during a low-dose insulin infusion in 9 subjects with various degrees of hepatic steatosis as determined using liver biopsy. Splanchnic balance of endocannabinoids and individual lipids was determined using ultra performance liquid chromatography coupled to mass spectrometry. RESULTS Concentrations of the endocannabinoid 2-arachidonoylglycerol were higher in arterialized (91 ± 33 μg/L basally) than in hepatic venous (51 ± 19 μg/L; P < .05) plasma. Fasting arterial (r = 0.72; P = .031) and hepatic venous (r = 0.70; P = .037) concentrations of 2-arachidonoylglycerol were related positively to liver fat content. Analysis of fluxes of 85 different triglycerides showed that the fatty liver overproduces saturated triglycerides. In the plasma FFA fraction in the basal state, the relative amounts of palmitoleate and linoleate were lower and those of stearate and oleate were higher in the hepatic vein than in the artery. Absolute concentrations of all nontriglyceride lipids were comparable in arterialized venous plasma and the hepatic vein both in the basal and insulin-stimulated states. CONCLUSIONS The human fatty liver takes up 2-arachidonoylglycerol and overproduces triacylglycerols containing saturated fatty acids, which might reflect increased de novo lipogenesis.

Development of a Germination Process for Producing High β-Glucan, Whole Grain Food Ingredients from Oat

ABSTRACT Germination can be used to improve the texture and flavor of cereals. However, germination generally causes breakdown of β-glucans, which is undesirable with respect to the functional properties of β-glucan. Our aim was to assess possibilities of germinating oat without substantial loss of high molecular weight β-glucan. Two cultivars, hulled Veli and hull-less (naked) Lisbeth were germinated at 5, 15, and 25°C and dried by lyophilization or oven drying. Elevated germination temperatures led to an increase in Fusarium, aerobic heterotrophic bacteria, Pseudomonas spp., lactic acid bacteria, enterobacteria, and aerobic spore-forming bacteria. Therefore, the germination temperature should be kept low to avoid excessive growth of microbes. Of the samples germinated at 15°C, only one contained low amounts of the Fusarium toxin deoxynivalenol (52 μg/kg). Germination led to the breakdown of β-glucans, but the decrease in the molecular weight of β-glucan was initially very slow. A short germination sched...

Plasticization of barley starch with glycerol and water

Abstract Barley starch was plasticized in a melt mixer using glycerol and water as plasticizers. Plasticizer concentration, time, temperature, and shear were varied, and their effects on the molecular weight of starch and the glass transition temperature and mechanical properties of the mixtures were studied. Depolymerization of amylopectin was observed in all experiments, and starch degradation proceeded further at low glycerol concentrations. The glass transition of the plasticized starch-glycerol mixtures occurred in the temperature range −50 to −100°C and was probably induced by glycerol, not by starch. The tensile strength of a starch plate containing 29 wt% glycerol was about 0.5 MPa 1 week after molding, but increased to 2–3 MPa during 5 weeks of storage at 50% relative humidity and 24°C.

Mechanical and permeability properties of biodegradable extruded starch/polycaprolactone films

Barley starch and glycerol were mixed with polycaprolactone (PCL) powder in various combinations and plasticized in a twin-screw extruder. When possible, extrudates were processed into films in a single-screw extruder and subjected to an orientation process with the aim of improving the water durability and mechanical strength of the starch films. The mechanical properties, water vapour and oxygen permeabilities, sorption isotherms and solubility of the processed films were studied. The films containing 20% or more PCL achieved a tensile strength of 20 MPa or higher. Orientation of the film still further improved the tensile strength, and also the water vapour and oxygen barrier properties. With PCL contents of 0–20% the starch/PCL films proved to be excellent oxygen barriers. Increase in PCL content beyond this impaired the oxygen barrier properties, whilst improving the water barrier properties. Copyright