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1.
  • Bellman, Jakob, et al. (författare)
  • Loading enhances glucose uptake in muscles, bones, and bone marrow of lower extremities in humans.
  • 2024
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197.
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased standing time has been associated with improved health, but the underlying mechanism is unclear.We herein investigate if increased weight loading increases energy demand and thereby glucose uptake (GU) locally in bone and/or muscle in the lower extremities.In this single-center clinical trial with randomized crossover design (ClinicalTrials.gov ID, NCT05443620), we enrolled 10 men with body mass index (BMI) between 30 and 35kg/m2. Participants were treated with both high load (standing with weight vest weighing 11% of body weight) and no load (sitting) on the lower extremities. GU was measured using whole-body quantitative positron emission tomography/computed tomography (PET/CT) imaging. The primary endpoint was the change in GU ratio between loaded bones (i.e. femur and tibia) and non-loaded bones (i.e. humerus).High load increased the GU ratio between lower and upper extremities in cortical diaphyseal bone (e.g. femur/humerus ratio increased by 19%, p=0.029), muscles (e.g. m. quadriceps femoris/m. triceps brachii ratio increased by 28%, p=0.014) and in certain bone marrow regions (femur/humerus diaphyseal bone marrow region ratio increased by 17%, p=0.041). Unexpectedly, we observed the highest GU in the bone marrow region of vertebral bodies, but its GU was not affected by high load.Increased weight-bearing loading enhances GU in muscles, cortical bone, and bone marrow of the exposed lower extremities. This could be interpreted as increased local energy demand in bone and muscle caused by increased loading. The physiological importance of the increased local GU by static loading remains to be determined.
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2.
  • Garthwaite, Taru, et al. (författare)
  • Associations of sedentary time, physical activity, and fitness with muscle glucose uptake in adults with metabolic syndrome
  • 2022
  • Ingår i: Scandinavian Journal of Medicine and Science in Sports. - West Sussex : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 33:3, s. 353-358
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The objective of the study was to investigate the associations of sedentary time, physical activity, and cardiorespiratory fitness with skeletal muscle glucose uptake (GU). Methods: Sedentary time and physical activity were measured with accelerometers and VO2max with cycle ergometry in 44 sedentary adults with metabolic syndrome. Thigh muscle GU was determined with [18F]FDG-PET imaging. Results: Sedentary time (β = −0.374), standing (β = 0.376), steps (β = 0.351), and VO2max (β = 0.598) were associated with muscle GU when adjusted for sex, age, and accelerometer wear time. Adjustment for body fat-% turned all associations non-significant. Conclusion: Body composition is a more important determinant of muscle GU in this population than sedentary time, physical activity, or fitness. © 2022 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.
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3.
  • Garthwaite, Taru, et al. (författare)
  • Effects of reduced sedentary time on cardiometabolic health in adults with metabolic syndrome : A three-month randomized controlled trial
  • 2022
  • Ingår i: Journal of Science and Medicine in Sport. - Chatswood : Elsevier Ltd. - 1440-2440 .- 1878-1861. ; 25:7, s. 579-585
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To investigate if reducing sedentary behavior improves cardiometabolic biomarkers in adults with metabolic syndrome. Design: Randomized controlled trial. Methods: Sixty-four sedentary middle-aged adults with metabolic syndrome were randomized into intervention (INT; n = 33) and control (CON; n = 31) groups. INT was guided to limit sedentary behavior by 1 h/day through increased standing and light-intensity physical activity. CON was instructed to maintain usual habits. Sedentary behavior, breaks in sedentary behavior, standing, and physical activity were measured with hip-worn accelerometers for three months. Fasting blood sampling and measurements of anthropometrics, body composition, and blood pressure were performed at baseline and at three months. Linear mixed models were used for statistical analyses. Results: INT reduced sedentary behavior by 50 (95% CI: 24, 73) min/day by increasing light-intensity and moderate-to-vigorous physical activity (19 [8, 30] and 24 [14, 34] min/day, respectively). Standing increased also, but non-significantly (6 [−11, 23] min/day). CON maintained baseline activity levels. Significant intervention effects favoring INT occurred in fasting insulin (INT: 83.4 [68.7, 101.2] vs. CON: 102.0 [83.3, 125.0] pmol/l at three months), insulin resistance (HOMA-IR; 3.2 [2.6, 3.9] vs. 4.0 [3.2, 4.9]), HbA1c (37 [36, 38] vs. 38 [37, 39] mmol/mol), and liver enzyme alanine aminotransferase (28 [24, 33] vs. 33 [28, 38] U/l). Conclusions: Reducing sedentary behavior by 50 min/day and increasing light-intensity and moderate-to-vigorous activity showed benefits in several cardiometabolic biomarkers in adults with metabolic syndrome. Replacing some of the daily sedentary behavior with light-intensity and moderate-to-vigorous physical activity may help in cardiometabolic disease prevention in risk populations. © 2022 The Authors
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4.
  • Garthwaite, Taru, et al. (författare)
  • Standing is associated with insulin sensitivity in adults with metabolic syndrome
  • 2021
  • Ingår i: Journal of Science and Medicine in Sport. - Chatswood : Elsevier. - 1440-2440 .- 1878-1861. ; 24:12, s. 1255-1260
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To determine how components of accelerometer-measured sedentary behavior (SB) and physical activity (PA), and fitness are associated with insulin sensitivity in adults with metabolic syndrome. Design: Cross-sectional. Methods: Target population was middle-aged (40–65 years) sedentary adults with metabolic syndrome. SB, breaks in SB, standing, and PA were measured for four weeks with hip-worn accelerometers. VO2max (ml/min/kg) was measured with maximal cycle ergometry. Insulin sensitivity was determined by hyperinsulinaemic-euglycaemic clamp (M-value) and fasting blood sampling (HOMA-IR, insulin). Multivariable regression was used for analyses. Results: Sixty-four participants (37 women; 58.3 [SD 6.8] years) were included. Participants spent 10.0 (1.0) h sedentary, 1.8 (0.6) h standing, and 2.7 (0.6) h in PA and took 5149 (1825) steps and 29 (8) breaks daily. In sex-, age- and accelerometer wear time-adjusted model SB, standing, steps and VO2max were associated with M-value (β = −0.384; β = 0.400; β = 0.350; β = 0.609, respectively), HOMA-IR (β = 0.420; β = −0.548; β = −0.252; β = −0.449), and insulin (β = 0.433; β = −0.541; β = −0.252; β = −0.453); all p-values < 0.05. Breaks associated only with M-value (β = 0.277). When further adjusted for body fat %, only standing remained significantly associated with HOMA-IR (β = −0.381) and insulin (β = −0.366); significance was maintained even when further adjusted for SB, PA and fitness. Light and moderate-to-vigorous PA were not associated with insulin sensitivity. Conclusions: Standing is associated with insulin sensitivity markers. The association with HOMA-IR and insulin is independent of adiposity, PA, SB and fitness. Further studies are warranted, but these findings encourage replacing sitting with standing for potential improvements in insulin sensitivity in adults at increased type 2 diabetes risk. © 2021 The Authors.
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5.
  • Haapala, Eero A., et al. (författare)
  • Association between cardiorespiratory fitness and metabolic health in overweight and obese adults
  • 2022
  • Ingår i: Journal of Sports Medicine and Physical Fitness. - Turin : Edizioni Minerva Medica. - 0022-4707 .- 1827-1928. ; 62:11, s. 1526-1533
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cardiorespiratory fitness (CRF) has been inversely associated with insulin resistance and clustering of cardiometabolic risk factors among overweight and obese individuals. However, most previous studies have scaled CRF by body mass (BM) possibly inflating the association between CRF and cardiometabolic health. We investigated the associations of peak oxygen uptake (V?O2peak) and peak power output (Wpeak) scaled either by BM-1, fat free mass (FFM-1), or by allometric methods with individual cardiometabolic risk factors and clustering of cardiometabolic risk factors in 55 overweight or obese adults with metabolic syndrome. METHODS: VO2peak and Wpeak were assessed by a maximal cycle ergometer exercise test. FFM was measured by air displacement plethysmo- graph and glucose, insulin, HbA1c, triglycerides, and total, LDL, and HDL cholesterol from fasting blood samples. HOMA-IR and metabolic syndrome score (MetS) were computed. RESULTS: VO2peak and Wpeak scaled by BM-1 were inversely associated with insulin (β=-0.404 to -0.372, 95% CI: -0.704 to -0.048), HOMAIR (β=-0.442 to -0.440, 95% CI: -0.762 to -0.117), and MetS (β=-0.474 to -0.463, 95% CI: -0.798 to -0.127). Other measures of CRF were not associated with cardiometabolic risk factors. CONCLUSIONS: Our results suggest that using BM-1 as a scaling factor confounds the associations between CRF and cardiometabolic risk in overweight/obese adults with the metabolic syndrome. © 2022 EDIZIONI MINERVA MEDICA.
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6.
  • Heid, Iris M, et al. (författare)
  • Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
  • Tidskriftsartikel (refereegranskat)abstract
    • Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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7.
  • Laine, Saara, et al. (författare)
  • Relationship between liver fat content and lifestyle factors in adults with metabolic syndrome
  • 2022
  • Ingår i: Scientific Reports. - London : Nature Publishing Group. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the associations between liver fat content (LFC), sedentary behaviour (SB), physical activity (PA), fitness, diet, body composition, and cardiometabolic risk factors in adults with metabolic syndrome. A total of 44 sedentary adults (mean age 58 [SD 7] years; 25 women) with overweight or obesity participated. LFC was assessed with magnetic resonance spectroscopy and imaging, SB and PA with hip-worn accelerometers (26 [SD 3] days), fitness by maximal bicycle ergometry, body composition by air displacement plethysmography and nutrient intake by 4-day food diaries. LFC was not independently associated with SB, PA or fitness. Adjusted for sex and age, LFC was associated with body fat%, body mass index, waist circumference, triglycerides, alanine aminotransferase, and with insulin resistance markers. There was and inverse association between LFC and daily protein intake, which persisted after further adjusment with body fat%. LFC is positively associated with body adiposity and cardiometabolic risk factors, and inversely with daily protein intake. SB, habitual PA or fitness are not independent modulators of LFC. However, as PA is an essential component of healthy lifestyle, it may contribute to liver health indirectly through its effects on body composition in adults with metabolic syndrome. © 2022, The Author(s).
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8.
  • Lango Allen, Hana, et al. (författare)
  • Hundreds of variants clustered in genomic loci and biological pathways affect human height.
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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9.
  • Matilainen, Johanna, et al. (författare)
  • Increased secretion of adipocyte-derived extracellular vesicles is associated with adipose tissue inflammation and the mobilization of excess lipid in human obesity
  • 2024
  • Ingår i: JOURNAL OF TRANSLATIONAL MEDICINE. - 1479-5876. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundObesity is a worldwide epidemic characterized by adipose tissue (AT) inflammation. AT is also a source of extracellular vesicles (EVs) that have recently been implicated in disorders related to metabolic syndrome. However, our understanding of mechanistic aspect of obesity's impact on EV secretion from human AT remains limited.MethodsWe investigated EVs from human Simpson Golabi Behmel Syndrome (SGBS) adipocytes, and from AT as well as plasma of subjects undergoing bariatric surgery. SGBS cells were treated with TNF alpha, palmitic acid, and eicosapentaenoic acid. Various analyses, including nanoparticle tracking analysis, electron microscopy, high-resolution confocal microscopy, and gas chromatography-mass spectrometry, were utilized to study EVs. Plasma EVs were analyzed with imaging flow cytometry.ResultsEVs from mature SGBS cells differed significantly in size and quantity compared to preadipocytes, disagreeing with previous findings in mouse adipocytes and indicating that adipogenesis promotes EV secretion in human adipocytes. Inflammatory stimuli also induced EV secretion, and altered EV fatty acid (FA) profiles more than those of cells, suggesting the role of EVs as rapid responders to metabolic shifts. Visceral AT (VAT) exhibited higher EV secretion compared to subcutaneous AT (SAT), with VAT EV counts positively correlating with plasma triacylglycerol (TAG) levels. Notably, the plasma EVs of subjects with obesity contained a higher number of adiponectin-positive EVs than those of lean subjects, further demonstrating higher AT EV secretion in obesity. Moreover, plasma EV counts of people with obesity positively correlated with body mass index and TNF expression in SAT, connecting increased EV secretion with AT expansion and inflammation. Finally, EVs from SGBS adipocytes and AT contained TAGs, and EV secretion increased despite signs of less active lipolytic pathways, indicating that AT EVs could be involved in the mobilization of excess lipids into circulation.ConclusionsWe are the first to provide detailed FA profiles of human AT EVs. We report that AT EV secretion increases in human obesity, implicating their role in TAG transport and association with adverse metabolic parameters, thereby emphasizing their role in metabolic disorders. These findings promote our understanding of the roles that EVs play in human AT biology and metabolic disorders.
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10.
  • Norha, Jooa, et al. (författare)
  • Effects of reducing sedentary behavior on cardiorespiratory fitness in adults with metabolic syndrome : A 6-month RCT
  • 2023
  • Ingår i: Scandinavian Journal of Medicine and Science in Sports. - Chichester : Wiley-Blackwell Publishing Inc.. - 0905-7188 .- 1600-0838. ; 33:8, s. 1452-1461
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction:Poor cardiorespiratory fitness (CRF) is associated with adverse health outcomes. Previous observational and cross-sectional studies have suggested that reducing sedentary behavior (SB) might improve CRF. Therefore, we investigated the effects of a 6-month intervention of reducing SB on CRF in 64 sedentary inactive adults with metabolic syndrome in a non-blind randomized controlled trial.Materials and Methods:In the intervention group (INT, n = 33), the aim was to reduce SB by 1 h/day for 6 months without increasing exercise training. Control group (CON, n = 31) was instructed to maintain their habitual SB and physical activity. Maximal oxygen uptake (VO2max) was measured by maximal graded bicycle ergometer test with respiratory gas measurements. Physical activity and SB were measured during the whole intervention using accelerometers.Results:Reduction in SB did not improve VO2max statistically significantly (group × time p > 0.05). Maximal absolute power output (Wmax) did not improve significantly but increased in INT compared to CON when scaled to fat free mass (FFM) (at 6 months INT 1.54 [95% CI: 1.41, 1.67] vs. CON 1.45 [1.32, 1.59] Wmax/kgFFM, p = 0.036). Finally, the changes in daily step count correlated positively with the changes in VO2max scaled to body mass and FFM (r = 0.31 and 0.30, respectively, p < 0.05).Discussion:Reducing SB without adding exercise training does not seem to improve VO2max in adults with metabolic syndrome. However, succeeding in increasing daily step count may increase VO2max. © 2023 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.
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