| 1. |
- Benrick, Anna, 1979, et al.
(författare)
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Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture
- 2017
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Ingår i: Faseb Journal. - : Federation of American Societies for Experimental Biology. - 0892-6638 .- 1530-6860. ; 31:8, s. 3288-3297
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Tidskriftsartikel (refereegranskat)abstract
- A single bout of low-frequency electroacupuncture (EA) causing muscle contractions increases whole-body glucose uptake in insulin-resistant rats. We explored the underlying mechanism of this finding and whether it can be translated into clinical settings. Changes in glucose infusion rate (GIR) were measured by euglycemic-hyperinsulinemic clamp during and after 45 min of low-frequency EA in 21 overweight/obese women with polycystic ovary syndrome (PCOS) and 21 controls matched for age, weight, and body mass index (experiment 1) and in rats receiving autonomic receptor blockers (experiment 2). GIR was higher after EA in controls and women with PCOS. Plasma serotonin levels and homovanillic acid, markers of vagal activity, decreased in both controls and patients with PCOS. Adipose tissue expression of pro-nerve growth factor (proNGF) decreased, and the mature NGF/proNGF ratio increased after EA in PCOS, but not in controls, suggesting increased sympathetic-driven adipose tissue metabolism. Administration of alpha-/beta-adrenergic receptor blockers in rats blocked the increase in GIR in response to EA. Muscarinic and dopamine receptor antagonist also blocked the response but with slower onset. In conclusion, a single bout of EA increases whole-body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.
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| 2. |
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| 3. |
- Fagman, Johan Bourghardt, 1980, et al.
(författare)
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The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice.
- 2015
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Ingår i: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860 .- 0892-6638. ; 29:4, s. 1540-1550
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Tidskriftsartikel (refereegranskat)abstract
- Androgens have important cardiometabolic actions in males, but their metabolic role in females is unclear. To determine the physiologic androgen receptor (AR)-dependent actions of androgens on atherogenesis in female mice, we generated female AR-knockout (ARKO) mice on an atherosclerosis-prone apolipoprotein E (apoE)-deficient background. After 8 weeks on a high-fat diet, but not on a normal chow diet, atherosclerosis in aorta was increased in ARKO females (+59% vs. control apoE-deficient mice with intact AR gene). They also displayed increased body weight (+18%), body fat percentage (+62%), and hepatic triglyceride levels, reduced insulin sensitivity, and a marked atherogenic dyslipidemia (serum cholesterol, +52%). Differences in atherosclerosis, body weight, and lipid levels between ARKO and control mice were abolished in mice that were ovariectomized before puberty, consistent with a protective action of ovarian androgens mediated via the AR. Furthermore, the AR agonist dihydrotestosterone reduced atherosclerosis (-41%; thoracic aorta), subcutaneous fat mass (-44%), and cholesterol levels (-35%) in ovariectomized mice, reduced hepatocyte lipid accumulation in hepatoma cells in vitro, and regulated mRNA expression of hepatic genes pivotal for lipid homeostasis. In conclusion, we demonstrate that the AR protects against diet-induced atherosclerosis in female mice and propose that this is mediated by modulation of body composition and lipid metabolism.-Fagman, J. B., Wilhelmson, A. S., Motta, B. M., Pirazzi, C., Alexanderson, C., De Gendt, K., Verhoeven, G., Holmäng, A., Anesten, F., Jansson, J. -O., Levin, M., Borén, J., Ohlsson, C., Krettek, A., Romeo, S., Tivesten, A. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice.
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| 4. |
- Han, Hongya, et al.
(författare)
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Human 15-lipoxygenase-1 is a regulator of dendritic-cell spreading and podosome formation
- 2017
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Ingår i: The FASEB Journal. - : FEDERATION AMER SOC EXP BIOL. - 0892-6638 .- 1530-6860. ; 31:2, s. 491-504
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) involved in proinflammatory immune responses derive mainly from peripheral monocytes, and the cells subsequently mature and migrate into the inflammatory micromilieu. Here we report that suppressing of 15-lipoxygenase-1 led to a substantial reduction in DC spreading and podosome formation in vitro. The surface expression of CD83 was significantly lower in both sh-15-lipoxygenase-1 (15-LOX-1)-transduced cells and DCs cultivated in the presence of a novel specific 15-LOX-1 inhibitor. The T-cell response against tetanus-pulsed DCs was only affected to a minor extent on inhibition of 15-LOX-1. In contrast, endocytosis and migration ability of DCs were significantly suppressed on 15-LOX-1 inhibition. The expression of 15-LOX-1 in DCs was also demonstrated in affected human skin in atopic and contact dermatitis, showing that the enzyme is indeed expressed in inflammatory diseases in vivo. This study demonstrated that inhibiting 15-LOX-1 led to an impaired podosome formation in DCs, and consequently suppressed antigen uptake and migration capacity. These results indicated that 15-LOX-1 is a potential target for inhibiting the trafficking of DCs to lymphoid organs and inflamed tissues and decreasing the inflammatory response attenuating symptoms of certain immunologic and inflammatory disorders such as dermatitis.-Han, H., Liang, X., Ekberg, M., Kritikou, J. S., Brunnstro " m, angstrom., Pelcman, B., Matl, M., Miao, X., Andersson, M., Yuan, X., Schain, F., Parvin, S., Melin, E., Sjoberg, J., Xu, D., Westerberg, L. S., Bjorkholm, M., Claesson, H.- E. Human 15-lipoxygenase- 1 is a regulator of dendritic-cell spreading and podosome formation.
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| 5. |
- Kassem, Ali, et al.
(författare)
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TLR5, a novel mediator of innate immunity-induced osteoclastogenesis and bone loss
- 2015
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Ingår i: Faseb Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 29:11, s. 4449-4460
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence points to the importance of the innate immune system in inflammation-induced bone loss in infectious and autoimmune diseases. TLRs are well known for being activated by ligands expressed by bacteria, viruses, and fungi. Recent findings indicate that also endogenous ligands in inflammatory processes are important, one being a TLR5 agonist present in synovial fluid from patients with rheumatoid arthritis (RA). We found that activation of TLR5 by its specific ligand, flagellin, caused robust osteoclast formation and bone loss in cultured mouse neonatal parietal bones dependent on increased receptor activator of NF-kappa B ligand (RANKL): osteoprotegerin ratio, with half-maximal stimulation at 0.01 mu g/ml. Flagellin enhanced Rankl mRNA in isolated osteoblasts by a myeloid differentiation primary response gene 88 and NF-kappa B-dependent mechanism. Injection of flagellin locally over skull bones in 5-wk-oldmice resulted in increased mRNA expression of Rankl and osteoclastic genes, robust osteoclast formation, and bone loss. The effects in vitro and in vivo were absent in Tlr5(-/-) mice. These data show that TLR5 is a novel activator of RANKL and osteoclast formation and, therefore, a potential key factor in inflammation-induced bone erosions in diseases like RA, reactive arthritis, and periodontitis. TLR5 might be a promising novel treatment target for prevention of inflammatory bone loss.
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| 6. |
- Nilsson, Torbjörn K, et al.
(författare)
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Plasma 1-carbon metabolites and academic achievement in 15-yr-old adolescents
- 2016
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Ingår i: The FASEB Journal. - Bethesda, USA : Federation of American Societies for Experimental Biology. - 0892-6638 .- 1530-6860. ; 30:4, s. 1683-1688
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Tidskriftsartikel (refereegranskat)abstract
- Academic achievement in adolescents is correlated with 1-carbon metabolism (1-CM), as folate intake is positively related and total plasma homocysteine (tHcy) negatively related to academic success. Because another 1-CM nutrient, choline is essential for fetal neurocognitive development, we hypothesized that choline and betaine could also be positively related to academic achievement in adolescents. In a sample of 15-yr-old children (n = 324), we measured plasma concentrations of homocysteine, choline, and betaine and genotyped them for 2 polymorphisms with effects on 1-CM, methylenetetrahydrofolate reductase (MTHFR) 677C>T, rs1801133, and phosphatidylethanolamine N-methyltransferase (PEMT), rs12325817 (G>C). The sum of school grades in 17 major subjects was used as an outcome measure for academic achievement. Lifestyle and family socioeconomic status (SES) data were obtained from questionnaires. Plasma choline was significantly and positively associated with academic achievement independent of SES factors (paternal education and income, maternal education and income, smoking, school) and of folate intake (P = 0.009, R-2 = 0.285). With the addition of the PEMT rs12325817 polymorphism, the association value was only marginally changed. Plasma betaine concentration, tHcy, and the MTHFR 677C>T polymorphism did not affect academic achievement in any tested model involving choline. Dietary intake of choline is marginal in many adolescents and may be a public health concern.
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| 7. |
- Pattanaik, Bagmi, 1977, et al.
(författare)
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Polymorphisms in alpha 7 nicotinic acetylcholine receptor gene, CHRNA7, and its partially duplicated gene, CHRFAM7A, associate with increased inflammatory response in human peripheral mononuclear cells
- 2022
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Ingår i: Faseb Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 36:5
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Tidskriftsartikel (refereegranskat)abstract
- The vagus nerve can, via the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR), regulate inflammation. The gene coding for the alpha 7nAChR, CHRNA7, can be partially duplicated, that is, CHRFAM7A, which is reported to impair the anti-inflammatory effect mediated via the alpha 7nAChR. Several single nucleotide polymorphisms (SNPs) have been described in both CHRNA7 and CHRFAM7A, however, the functional role of these SNPs for immune responses remains to be investigated. In the current study, we set out to investigate whether genetic variants of CHRNA7 and CHRFAM7A can influence immune responses. By investigating data available from the Swedish SciLifeLab SCAPIS Wellness Profiling (S3WP) study, in combination with droplet digital PCR and freshly isolated PBMCs from the S3WP participants, challenged with lipopolysaccharide (LPS), we show that CHRNA7 and CHRFAM7A are expressed in human PBMCs, with approximately four times higher expression of CHRFAM7A compared with CHRNA7. One SNP in CHRFAM7A, rs34007223, is positively associated with hsCRP in healthy individuals. Furthermore, gene ontology (GO)-terms analysis of plasma proteins associated with gene expression of CHRNA7 and CHRFAM7A demonstrated an involvement for these genes in immune responses. This was further supported by in vitro data showing that several SNPs in both CHRNA7 and CHRFAM7A are significantly associated with cytokine response. In conclusion, genetic variants of CHRNA7 and CHRFAM7A alters cytokine responses. Furthermore, given that CHRFAM7A SNP rs34007223 is associated with inflammatory marker hsCRY in healthy individuals suggests that CHRFAM7A may have a more pronounced role in regulating inflammatory processes in humans than previously been recognized.
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| 8. |
- Strålberg, Fredrik, et al.
(författare)
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Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling.
- 2013
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Ingår i: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860 .- 0892-6638. ; 27:7, s. 2687-701
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Tidskriftsartikel (refereegranskat)abstract
- The cysteine proteinase inhibitor cystatin C inhibited RANKL-stimulated osteoclast formation in mouse bone marrow macrophage cultures, an effect associated with decreased mRNA expression of Acp5, Calcr, Ctsk, Mmp9, Itgb3, and Atp6i, without effect on proliferation or apoptosis. The effects were concentration dependent with half-maximal inhibition at 0.3 μM. Cystatin C also inhibited osteoclast formation when RANKL-stimulated osteoclasts were cultured on bone, leading to decreased formation of resorption pits. RANKL-stimulated cells retained characteristics of phagocytotic macrophages when cotreated with cystatin C. Three other cysteine proteinase inhibitors, cystatin D, Z-RLVG-CHN2 (IC50 0.1 μM), and E-64 (IC50 3 μM), also inhibited osteoclast formation in RANKL-stimulated macrophages. In addition, cystatin C, Z-RLVG-CHN2, and E-64 inhibited osteoclastic differentiation of RANKL-stimulated CD14(+) human monocytes. The effect by cystatin C on differentiation of bone marrow macrophages was exerted at an early stage after RANKL stimulation and was associated with early (4 h) inhibition of c-Fos expression and decreased protein and nuclear translocation of c-Fos. Subsequently, p52, p65, IκBα, and Nfatc1 mRNA were decreased. Cystatin C was internalized in osteoclast progenitors, a process requiring RANKL stimulation. These data show that cystatin C inhibits osteoclast differentiation and formation by interfering intracellularly with signaling pathways downstream RANK.
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| 9. |
- Vizlin-Hodzic, Dzeneta, et al.
(författare)
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Developmental studies of Xenopus shelterin complexes: the message to reset telomere length is already present in the egg
- 2009
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Ingår i: FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 23:8, s. 2587-2594
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Tidskriftsartikel (refereegranskat)abstract
- The 6-protein complex shelterin protects the telomeres of human chromosomes. The recent discovery that telomeres are important for epigenetic gene regulation and vertebrate embryonic development calls for the establishment of model organisms to study shelterin and telomere function under normal developmental conditions. Here, we report the sequences of the shelterin-encoding genes in Xenopus laevis and its close relation Xenopus tropicalis. In vitro expression and biochemical characterization of the Xenopus shelterin proteins TRF1, TRF2, POT1, TIN2, RAP1, TPP1, and the shelterin accessory factor PINX1 indicate that all main functions of their human orthologs are conserved in Xenopus. The XlTRF1 and XtTRF1 proteins bind double-stranded telomeric DNA sequence specifically and interact with XlTIN2 and XtTIN2, respectively. Similarly, the XlTRF2 and XtTRF2 proteins bind double-stranded telomeric DNA and interact with XlRAP1 and XtRAP1, respectively, whereas the XlPOT1 and XtPOT1 proteins bind single stranded telomeric DNA. Real-time PCR further reveals the gene expression profiles for telomerase and the shelterin genes during embryogenesis. Notably, the composition of shelterin and the formation of its subcomplexes appear to be temporally regulated during embryonic development. Moreover, unexpectedly high telomerase and shelterin gene expression during early embryogenesis may reflect a telomere length resetting mechanism, similar to that reported for induced pluripotent stem cells and for animals cloned through somatic nuclear transfer.
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| 10. |
- Apró, William, et al.
(författare)
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Leucine does not affect mechanistic target of rapamycin complex 1 assembly but is required for maximal ribosomal protein s6 kinase 1 activity in human skeletal muscle following resistance exercise
- 2015
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 29:10, s. 4358-4373
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Tidskriftsartikel (refereegranskat)abstract
- We examined how the stimulatory effect of leucine on the mechanistic target of rapamycin complex 1 (mTORC1) pathway is affected by the presence of the remaining essential amino acids (EAAs). Nine male subjects performed resistance exercise on 4 occasions and were randomly supplied EAAs with leucine, EAAs without leucine (EAA-Leu), leucine alone, or flavored water (placebo; control). Muscle biopsies were taken from the vastus lateralis before and 60 and 90 min after exercise. Biopsies were analyzed for protein phosphorylation, kinase activity, protein-protein interactions, amino acid concentrations, and tracer incorporation. Leucine alone stimulated ribosomal protein s6 kinase 1 (S6K1) phosphorylation similar to 280% more than placebo and EAA-Leu after exercise. Moreover, this response was enhanced by 60-75% after intake of EAAs compared with that of leucine alone (P < 0.05). Kinase activity of S6K1 reflected that of S6K1 phosphorylation; 60 min after exercise, the activity was elevated 3.3- and 4.2-fold with intake of leucine alone and with EAAs, respectively (P < 0.05). The interaction between mammalian target of rapamycin and regulatory-associated protein of mammalian target of rapamycin was unaltered in response to both resistance exercise and amino acid provision. Leucine alone stimulates mTORC1 signaling, although this response is enhanced by other EAAs and does not appear to be caused by alterations inmTORC1 assembly.
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