SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Jørgensen Sine W.) ;mspu:(article)"

Sökning: WFRF:(Jørgensen Sine W.) > Tidskriftsartikel

  • Resultat 1-6 av 6
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Broholm, Christa, et al. (författare)
  • Epigenetic programming of adipose-derived stem cells in low birthweight individuals
  • 2016
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:12, s. 2664-2673
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: Low birthweight (LBW) is associated with dysfunctions of adipose tissue and metabolic disease in adult life. We hypothesised that altered epigenetic and transcriptional regulation of adipose-derived stem cells (ADSCs) could play a role in programming adipose tissue dysfunction in LBW individuals. Methods: ADSCs were isolated from the subcutaneous adipose tissue of 13 normal birthweight (NBW) and 13 LBW adult men. The adipocytes were cultured in vitro, and genome-wide differences in RNA expression and DNA methylation profiles were analysed in ADSCs and differentiated adipocytes. Results: We demonstrated that ADSCs from LBW individuals exhibit multiple expression changes as well as genome-wide alterations in methylation pattern. Reduced expression of the transcription factor cyclin T2 encoded by CCNT2 may play a key role in orchestrating several of the gene expression changes in ADSCs from LBW individuals. Indeed, silencing of CCNT2 in human adipocytes decreased leptin secretion as well as the mRNA expression of several genes involved in adipogenesis, including MGLL, LIPE, PPARG, LEP and ADIPOQ. Only subtle genome-wide mRNA expression and DNA methylation changes were seen in mature cultured adipocytes from LBW individuals. Conclusions/interpretation: Epigenetic and transcriptional changes in LBW individuals are most pronounced in immature ADSCs that in turn may programme physiological characteristics of the mature adipocytes that influence the risk of metabolic diseases. Reduced expression of CCNT2 may play a key role in the developmental programming of adipose tissue.
  •  
2.
  • Broholm, Christa, et al. (författare)
  • Epigenome- and Transcriptome-wide Changes in Muscle Stem Cells from Low Birth Weight Men
  • 2020
  • Ingår i: Endocrine Research. - : Informa UK Limited. - 0743-5800 .- 1532-4206. ; 45:1, s. 58-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Being born with low birth weight (LBW) is a risk factor for muscle insulin resistance and type 2 diabetes (T2D), which may be mediated by epigenetic mechanisms programmed by the intrauterine environment. Epigenetic mechanisms exert their prime effects in developing cells. We hypothesized that muscle insulin resistance in LBW subjects may be due to early differential epigenomic and transcriptomic alterations in their immature muscle progenitor cells. Results: Muscle progenitor cells were obtained from 23 healthy young adult men born at term with LBW, and 15 BMI-matched normal birth weight (NBW) controls. The cells were subsequently cultured and differentiated into myotubes. DNA and RNA were harvested before and after differentiation for genome-wide DNA methylation and RNA expression measurements. After correcting for multiple comparisons (q ≤ 0.05), 56 CpG sites were found to be significantly, differentially methylated in myoblasts from LBW compared with NBW men, of which the top five gene-annotated CpG sites (SKI, ARMCX3, NR5A2, NEUROG, ESRRG) previously have been associated to regulation of cholesterol, fatty acid and glucose metabolism and muscle development or hypertrophy. LBW men displayed markedly decreased myotube gene expression levels of the AMPK-repressing tyrosine kinase gene FYN and the histone deacetylase gene HDAC7. Silencing of FYN and HDAC7 was associated with impaired myotube formation, which for HDAC7 reduced muscle glucose uptake. Conclusions: The data provides evidence of impaired muscle development predisposing LBW individuals to T2D is linked to and potentially caused by distinct DNA methylation and transcriptional changes including down regulation of HDAC7 and FYN in their immature myoblast stem cells.
  •  
3.
  • Hjort, Line, et al. (författare)
  • 36 h fasting of young men influences adipose tissue DNA methylation of LEP and ADIPOQ in a birth weight-dependent manner
  • 2017
  • Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Subjects born with low birth weight (LBW) display a more energy-conserving response to fasting compared with normal birth weight (NBW) subjects. However, the molecular mechanisms explaining these metabolic differences remain unknown. Environmental influences may dynamically affect epigenetic marks, also in postnatal life. Here, we aimed to study the effects of short-term fasting on leptin (LEP) and adiponectin (ADIPOQ) DNA methylation and gene expression in subcutaneous adipose tissue (SAT) from subjects with LBW and NBW. Methods: Twenty-one young LBW men and 18 matched NBW controls were studied during 36 h fasting. Eight subjects from each group completed a control study (overnight fast). We analyzed SAT LEP and ADIPOQ methylation (Epityper MassARRAY), gene expression (q-PCR), and adipokine plasma levels. Results: After overnight fast (control study), LEP and ADIPOQ DNA methylation levels were higher in LBW compared to those in NBW subjects (p ≤ 0.03) and increased with 36 h fasting in NBW subjects only (p ≤ 0.06). Both LEP and ADIPOQ methylation levels were positively associated with total body fat percentage (p ≤ 0.05). Plasma leptin levels were higher in LBW versus NBW subjects after overnight fasting (p = 0.04) and decreased more than threefold in both groups after 36 h fasting (p ≤ 0.0001). Conclusions: This is the first study to demonstrate that fasting induces changes in DNA methylation. This was shown in LEP and ADIPOQ promoters in SAT among NBW but not LBW subjects. The altered epigenetic flexibility in LBW subjects might contribute to their differential response to fasting, adipokine levels, and increased risk of metabolic disease.
  •  
4.
  • Rönn, Tina, et al. (författare)
  • Circulating triglycerides are associated with human adipose tissue DNA methylation of genes linked to metabolic disease
  • 2023
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 32:11, s. 1875-1887
  • Tidskriftsartikel (refereegranskat)abstract
    • Dysregulation of circulating lipids is a central element for the metabolic syndrome. However, it is not well established whether human subcutaneous adipose tissue is affected by or affect circulating lipids through epigenetic mechanisms. Hence, our aim was to investigate the association between circulating lipids and DNA methylation levels in human adipose tissue. DNA methylation and gene expression were analysed genome-wide in subcutaneous adipose tissue from two different cohorts, including 85 men and 93 women, respectively. Associations between DNA methylation and circulating levels of triglycerides, low-density lipoprotein, high-density lipoprotein and total cholesterol were analysed. Causal mediation analyses tested if adipose tissue DNA methylation mediates the effects of triglycerides on gene expression or insulin resistance. We found 115 novel associations between triglycerides and adipose tissue DNA methylation, e.g. in the promoter of RFS1, ARID2 and HOXA5 in the male cohort (P ≤ 1.1 × 10-7), and 63 associations, e.g. within the gene body of PTPRN2 and COL6A3 in the female cohort. We further connected these findings to altered mRNA expression levels in adipose tissue (e.g. HOXA5, IL11 and FAM45B). Interestingly, there was no overlap between methylation sites associated with triglycerides in men and the sites found in women, which points towards sex-specific effects of triglycerides on the epigenome. Finally, a causal mediation analysis provided support for adipose tissue DNA methylation as a partial mediating factor between circulating triglycerides and insulin resistance. This study identified novel epigenetic alterations in adipose tissue associated with circulating lipids. Identified epigenetic changes seem to mediate effects of triglycerides on insulin resistance.
  •  
5.
  • Rönn, Tina, et al. (författare)
  • Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood.
  • 2015
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:13, s. 3792-3813
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed DNA methylation of ∼480,000 sites in human adipose tissue from 96 males and 94 females, and related methylation to age, BMI and HbA1c. We also compared epigenetic signatures in adipose tissue and blood. Age was significantly associated with both altered DNA methylation and expression of 1,050 genes (e.g. FHL2, NOX4 and PLG). Interestingly, many reported epigenetic biomarkers of ageing in blood, including ELOVL2, FHL2, KLF14 and GLRA1, also showed significant correlations between adipose tissue DNA methylation and age in our study. The most significant association between age and adipose tissue DNA methylation was found upstream of ELOVL2. We identified 2,825 genes (e.g. FTO, ITIH5, CCL18, MTCH2, IRS1 and SPP1) where both DNA methylation and expression correlated with BMI. Methylation at previously reported HIF3A sites correlated significantly with BMI in females only. HbA1c (range 28-46 mmol/mol) correlated significantly with methylation of 711 sites, annotated to e.g. RAB37, TICAM1 and HLA-DPB1. Pathway analyses demonstrated that methylation levels associated with age and BMI are overrepresented among genes involved in cancer, type 2 diabetes and cardiovascular disease. Our results highlight the impact of age, BMI and HbA1c on epigenetic variation of candidate genes for metabolic diseases and cancer in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers in blood can mirror age-related epigenetic signatures in target tissues for metabolic diseases such as adipose tissue.
  •  
6.
  • Ström, Kristoffer, et al. (författare)
  • N1-methylnicotinamide is a signalling molecule produced in skeletal muscle coordinating energy metabolism
  • 2018
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is a major health problem, and although caloric restriction and exercise are successful strategies to lose adipose tissue in obese individuals, a simultaneous decrease in skeletal muscle mass, negatively effects metabolism and muscle function. To deeper understand molecular events occurring in muscle during weight-loss, we measured the expressional change in human skeletal muscle following a combination of severe caloric restriction and exercise over 4 days in 15 Swedish men. Key metabolic genes were regulated after the intervention, indicating a shift from carbohydrate to fat metabolism. Nicotinamide N-methyltransferase (NNMT) was the most consistently upregulated gene following the energy-deficit exercise. Circulating levels of N1-methylnicotinamide (MNA), the product of NNMT activity, were doubled after the intervention. The fasting-fed state was an important determinant of plasma MNA levels, peaking at ~18 h of fasting and being lowest ~3 h after a meal. In culture, MNA was secreted by isolated human myotubes and stimulated lipolysis directly, with no effect on glucagon or insulin secretion. We propose that MNA is a novel myokine that enhances the utilization of energy stores in response to low muscle energy availability. Future research should focus on applying MNA as a biomarker to identify individuals with metabolic disturbances at an early stage. 
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-6 av 6
Typ av publikation
Typ av innehåll
refereegranskat (6)
Författare/redaktör
Jørgensen, Sine W. (6)
Ling, Charlotte (5)
Vaag, Allan (5)
Perfilyev, Alexander (4)
Brøns, Charlotte (4)
Gillberg, Linn (4)
visa fler...
Hjort, Line (3)
Groop, Leif (2)
Volkov, Petr (2)
Rönn, Tina (2)
Eriksson, Karl-Fredr ... (2)
Ribel-Madsen, Rasmus (2)
Broholm, Christa (2)
Schrölkamp, Maren (2)
Scheele, Camilla (2)
Mortensen, Brynjulf (2)
Jansson, Per-Anders, ... (1)
Ahlqvist, Emma (1)
Hansson, Ola (1)
Wierup, Nils (1)
Zhou, Yuedan (1)
Almgren, Peter (1)
Pedersen, Oluf (1)
Hansen, Torben (1)
Stener-Victorin, Eli ... (1)
Eliasson, Lena (1)
Jönsson, Josefine (1)
Holmberg, Hans-Chris ... (1)
Olsson, Anders H (1)
Edlund, Anna (1)
Vaag, Allan A (1)
Fernandez, Celine (1)
Stener-Victorin, Eli ... (1)
Ström, Kristoffer (1)
Oskolkov, Nikolay (1)
Kokosar, Milana (1)
Stenkula, Karin G. (1)
Frystyk, Jan (1)
Calbet, José A L (1)
Morales-Alamo, David (1)
Hansen, Ninna S. (1)
Strasko, Klaudia S. (1)
Olsson, Anders Henri ... (1)
Ahlers, Juliane Mari ... (1)
Hansen, Ninna Schiøl ... (1)
Hingst, Janne (1)
Wojtaszewski, Jørgen (1)
Pedersen, Bente Klar ... (1)
Perez-Suarez, Ismael (1)
Martin-Rincon, Marco ... (1)
visa färre...
Lärosäte
Lunds universitet (5)
Göteborgs universitet (1)
Luleå tekniska universitet (1)
Mittuniversitetet (1)
Karolinska Institutet (1)
Språk
Engelska (6)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (6)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy