Comprehensive metabolic profile from childhood to adulthood – associations with dietary intervention and lifestyle risk factors. The Special Turku Coronary Risk Factor Intervention Project

BACKGROUND: Exposure to adverse lifestyle can lead to cardiovascular diseases in adulthood. Risk may be reduced with healthy diet, physical activity, and avoidance of tobacco smoke by inducing beneficial effects on metabolism, including serum lipoproteins and fatty acids. Still, little is known about these links at young age. PARTICIPANTS: This thesis is part of the prospective, randomized Special Turku Coronary Risk Factor Intervention Project (STRIP) aiming to influence risk factors of cardiovascular diseases mainly via dietary counselling. The repeated dietary intervention, with a key target to decrease intake of saturated fat, continued from age 7 months until age 20 years. Data on diet, physical activity and smoking habits were gathered by food records and questionnaires. Serum cotinine (indicator of tobacco smoke exposure) was measured using gas chromatography and metabolic measures were quantified by nuclear magnetic resonance metabolomics in 338–554 participants between the ages of 9 and 19. AIM: The aim of this thesis was to study the associations of dietary intervention, achieving the dietary targets of the intervention, physical activity, and exposure to tobacco smoke on a comprehensive metabolic profile from childhood to adulthood. RESULTS: The intervention reduced intake of saturated fat and increased intake of polyunsaturated fat. The intervention and physical activity were directly associated with a less saturated serum fatty acid profile with inverse associations seen for monounsaturated fatty acids ratio while the associations for tobacco smoke exposure were opposite. The intervention and dietary targets were inversely linked with lowdensity lipoprotein lipid concentrations. Physical activity was inversely associated with very-low-density lipoprotein (VLDL) concentration and size, and directly with high-density lipoprotein (HDL) particle concentration, size, and cholesterol. Passive tobacco smoke exposure was directly associated with VLDL particle size, and inversely associated with HDL particle size. Non-lipid results were mostly weak. CONCLUSIONS: Repeated dietary counselling, achieving its targets, or being physically active are beneficially associated with metabolic profile while exposure to tobacco smoke is detrimentally associated with circulating metabolic measures.  Kokonaisvaltainen metabolinen profiili lapsuudesta aikuisuuteen – yhteys ravitsemusinterventioon ja elämäntapatekijöihin Sepelvaltimotaudin riskitekijöiden interventioprojekti. TAUSTA: Haitalliset elintavat voivat johtaa kardiovaskulaarisairauksiin aikuisena. Riskiä voi pienentää ruokavalion, fyysisen aktiivisuuden, sekä vähäisen tupakansavualtistuksen tuomilla aineenvaihduntamuutoksilla, esim. lipoproteiineihin ja rasvahappoihin. Elintapojen yhteyksistä varhaisen iän aineenvaihduntaan tiedetään vähän. AINEISTO: Tämä väitöskirjatyö on osa prospektiivista, satunnaistettua Sepelvaltimotaudin Riskitekijöiden Interventioprojekti (STRIP) -tutkimusta, joka pyrkii vaikuttamaan kardiovaskulaarisairauksien riskitekijöihin pääasiassa ravitsemusneuvonnan keinoin. Toistuva ravitsemusinterventio, päätavoitteena vähentää tyydyttyneen rasvan saantia, jatkui 7-kuukauden iästä 20-vuotiaaksi asti. Tietoa ravitsemuksesta, fyysisestä aktiivisuudesta sekä tupakoinnista kerättiin ruokapäiväkirjoilla sekä kyselylomakkeilla. Seerumin kotiniini (tupakansavualtistuksen indikaattori) määritettiin kaasukromatografilla ja aineenvaihduntatuotteet kvantifioitiin ydinmagneettisella resonanssispektroskopialla 338–554 osallistujalta 9–19 vuoden iässä. TAVOITE: Tämän väitöskirjatutkimuksen tavoite oli tutkia ravitsemusintervention, intervention ravitsemustavoitteiden saavuttamisen, fyysisen aktiivisuuden sekä tupakansavualtistuksen yhteyttä metaboliseen profiiliin lapsuudesta aikuisuuteen. TULOKSET: Interventio vähensi tyydyttyneen rasvan ja lisäsi monityydyttymättömän rasvan saantia. Interventio sekä fyysinen aktiivisuus olivat suoraan yhteydessä seerumin vähemmän tyydyttyneeseen rasvahappoprofiiliin sekä kääntäen yhteydessä kertatyydyttymättömien rasvahappojen osuuteen, tupakansavualtistuksen yhteyksien ollessa vastakkaiset. Interventio ja ravitsemustavoitteet olivat kääntäen yhteydessä LDL-partikkelien lipidipitoisuuteen. Fyysinen aktiivisuus oli kääntäen yhteydessä VLDL-partikkelien lukumäärään ja kokoon sekä suoraan yhteydessä HDLpartikkelien lukumäärään, kokoon sekä kolesterolipitoisuuteen. Passiivinen tupakointi oli suoraan yhteydessä VLDL-partikkelien kokoon ja kääntäen yhteydessä HDL-partikkelien kokoon. Pienimolekyylisten yhdisteiden tulokset olivat pääosin heikkoja. JOHTOPÄÄTÖKSET: Toistuva ravitsemusneuvonta, sen tavoitteiden saavuttaminen ja fyysinen aktiivisuus ovat myönteisesti yhteydessä metaboliseen profiiliin kun taas tupakansavualtistus on haitallisesti yhteydessä verenkierron metaboliitteihin

Metabolic profiling of fatty liver in young and middle-aged adults : Cross-sectional and prospective analyses of the Young Finns Study

Nonalcoholic fatty liver is associated with obesity-related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34-49 years (19% prevalence). Cross-sectional associations as well as 4-year and 10-year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P <0.0007 for 60 measures in age-adjusted and sex-adjusted cross-sectional analyses). The strongest direct associations were observed for extremely large very-low-density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48-6.78), other very-low-density lipoprotein measures, and branched-chain amino acids (e.g., leucine OR = 2.94, 2.51-3.44). Strong inverse associations were observed for high-density lipoprotein measures, e.g., high-density lipoprotein size (OR = 0.36, 0.30-0.42) and several fatty acids including omega-6 (OR = 0.37, 0.32-0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P <0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. Conclusion: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (Hepatology 2017;65:491-500).Peer reviewe

Achievement of the Targets of the 20-Year Infancy-Onset Dietary Intervention-Association with Metabolic Profile from Childhood to Adulthood

The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9-19 years (n = 549-338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) = 80th age-specific percentile, and (4) sucrose intake = 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (>= 2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health

Effect of Infancy-onset Dietary Intervention On a Comprehensive Metabolic Profile from Childhood to Early Adulthood. The Special Turku Coronary Risk Factor Intervention Project (STRIP).

Siirretty Doriast

Achievement of the Targets of the 20-Year Infancy-Onset Dietary Intervention—Association with Metabolic Profile from Childhood to Adulthood

The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9–19 years (n = 549–338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) &lt; 1:2, (2) intake of SAFA &lt; 10% of total energy intake, (3) fiber intake ≥ 80th age-specific percentile, and (4) sucrose intake ≤ 20th age-specific percentile. Metabolic biomarkers were quantified by high-throughput nuclear magnetic resonance metabolomics. Better adherence to the dietary targets, regardless of study group allocation, was assoiated with higher serum proportion of PUFAs, lower serum proportion of SAFAs, and a higher degree of unsaturation of fatty acids. Achieving ≥ 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (≥2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health

Achievement of the targets of the 20-year infancy-onset dietary intervention:association with metabolic profile from childhood to adulthood

Abstract The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9–19 years (n = 549–338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) &lt; 1:2, (2) intake of SAFA &lt; 10% of total energy intake, (3) fiber intake ≥ 80th age-specific percentile, and (4) sucrose intake ≤ 20th age-specific percentile. Metabolic biomarkers were quantified by high-throughput nuclear magnetic resonance metabolomics. Better adherence to the dietary targets, regardless of study group allocation, was assoiated with higher serum proportion of PUFAs, lower serum proportion of SAFAs, and a higher degree of unsaturation of fatty acids. Achieving ≥ 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (≥2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health

Metabolic profiling of fatty liver in young and middle-aged adults:cross-sectional and prospective analyses of the young Finns study

Abstract Nonalcoholic fatty liver is associated with obesity-related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34–49 years (19% prevalence). Cross-sectional associations as well as 4-year and 10-year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P &lt; 0.0007 for 60 measures in age-adjusted and sex-adjusted cross-sectional analyses). The strongest direct associations were observed for extremely large very-low-density lipoprotein triglycerides (odds ratio [OR] 5 4.86 per 1 standard deviation, 95% confidence interval 3.48–6.78), other very-low-density lipoprotein measures, and branched-chain amino acids (e.g., leucine OR = 2.94, 2.51–3.44). Strong inverse associations were observed for high-density lipoprotein measures, e.g., high-density lipoprotein size (OR = 0.36, 0.30–0.42) and several fatty acids including omega-6 (OR = 0.37, 0.32–0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P &lt; 0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. Conclusion: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults