Torgrim Mikal Langleite

• Lee-Ødegård, Sindre; Gulseth, Hanne Løvdal; Langleite, Torgrim Mikal; Norheim, Frode; Olsen, Thomas; Refsum, Helga; Jensen, Jørgen; Birkeland, Kåre I. & Drevon, Christian A (2020). Branched-chain amino acid metabolism, insulin sensitivity and liver fat response to exercise training in sedentary dysglycaemic and normoglycaemic men. Diabetologia.  ISSN 0012-186X.  64, s 410- 423 . doi: 10.1007/s00125-020-05296-0
• Henriksen, Hege Berg; Henriksen, Christine; Ræder, Hanna; Kværner, Ane Sørlie; Skjetne, Anne Juul; Bøhn, Siv Kjølsrud; Paur, Ingvild; Langleite, Torgrim Mikal; Wiedswang, Gro; Smeland, Sigbjørn & Blomhoff, Rune (2019). Hvilke kostråd skal man gi til pasienter behandlet for tarmkreft?. Norsk Tidsskrift for Ernæring.  ISSN 1503-5034.  s 32- 36
• Lee-Ødegård, Sindre; Norheim, Frode; Langleite, Torgrim Mikal; Gulseth, Hanne Løvdal; Birkeland, Kåre I. & Drevon, Christian A (2019). Effects of long-term exercise on plasma adipokine levels and inflammation-related gene expression in subcutaneous adipose tissue in sedentary dysglycaemic, overweight men and sedentary normoglycaemic men of healthy weight. Diabetologia.  ISSN 0012-186X.  62(6), s 1048- 1064 . doi: 10.1007/s00125-019-4866-5 Fulltekst i vitenarkiv.
• Lee-Ødegård, Sindre; Norheim, Frode; Gulseth, Hanne Løvdal; Langleite, Torgrim Mikal; Aker, Andreas Helge Mikael; Gundersen, Thomas Erik; Holen, Torgeir; Birkeland, Kåre I. & Drevon, Christian A (2018). Skeletal muscle phosphatidylcholine and phosphatidylethanolamine respond to exercise and influence insulin sensitivity in men. Scientific Reports.  ISSN 2045-2322.  8:6531, s 1- 12 . doi: 10.1038/s41598-018-24976-x Fulltekst i vitenarkiv.
• Lee, Sindre; Norheim, Frode; Gulseth, Hanne Løvdal; Langleite, Torgrim Mikal; Kolnes, Kristoffer Jensen; Tangen, Daniel S.; Stadheim, Hans Kristian; Gilfillan, Gregor Duncan; Holen, Torgeir; Birkeland, Kåre I.; Jensen, Jørgen & Drevon, Christian A (2017). Interaction between plasma fetuin-A and free fatty acids predicts changes in insulin sensitivity in response to long-term exercise. Physiological Reports.  ISSN 2051-817X.  5(5) . doi: 10.14814/phy2.13183 Fulltekst i vitenarkiv. Vis sammendrag

  The hepatokine fetuin‐A can together with free fatty acids (FFAs) enhance adipose tissue (AT) inflammation and insulin resistance via toll‐like receptor 4 (TLR4). Although some of the health benefits of exercise can be explained by altered release of myokines from the skeletal muscle, it is not well documented if some of the beneficial effects of exercise can be explained by altered secretion of hepatokines. The aim of this study was to examine the effect of interaction between fetuin‐A and FFAs on insulin sensitivity after physical exercise. In this study, 26 sedentary men who underwent 12 weeks of combined endurance and strength exercise were included. Insulin sensitivity was measured using euglycemic‐hyperinsulinemic clamp, and AT insulin resistance was indicated by the product of fasting plasma concentration of FFAs and insulin. Blood samples and biopsies from skeletal muscle and subcutaneous AT were collected. Several phenotypic markers were measured, and mRNA sequencing was performed on the biopsies. AT macrophages were analyzed based on mRNA markers. The intervention improved hepatic parameters, reduced plasma fetuin‐A concentration (~11%, P < 0.01), slightly changed FFAs concentration, and improved glucose infusion rate (GIR) (~33%, P < 0.01) across all participants. The change in circulating fetuin‐A and FFAs interacted to predict some of the change in GIR (β = −42.16, P = 0.030), AT insulin resistance (β = 0.579, P = 0.003), gene expression related to TLR‐signaling in AT and AT macrophage mRNA (β = 94.10, P = 0.034) after exercise. We observed no interaction effects between FFAs concentrations and leptin and adiponectin on insulin sensitivity, or any interaction effects between Fetuin‐A and FFAs concentrations on skeletal muscle TLR‐signaling. The relationship between FFAs levels and insulin sensitivity seemed to be specific for fetuin‐A and the AT. Some of the beneficial effects of exercise on insulin sensitivity may be explained by changes in circulating fetuin‐A and FFAs, promoting less TLR4 signaling in AT perhaps by modulating AT macrophages.

• Lund, Jenny; Rustan, Arild; Løvsletten, Nils Gunnar; Mudry, Jonathan M.; Langleite, Torgrim Mikal; Feng, Yuan Zeng; Stensrud, Camilla; Brubak, Mari G; Drevon, Christian A; Birkeland, Kåre I.; Kolnes, Kristoffer Jensen; Johansen, Egil Ivar; Tangen, Daniel S.; Stadheim, Hans Kristian; Gulseth, Hanne Løvdal; Krook, Anna; Kase, Eili Tranheim; Jensen, Jørgen & Thoresen, G. Hege (2017). Exercise in vivo marks human myotubes in vitro: Training-induced increase in lipid metabolism. PLOS ONE.  ISSN 1932-6203.  12:e0175441(4), s 1- 24 . doi: 10.1371/journal.pone.0175441 Fulltekst i vitenarkiv.
• Pourteymour, Shirin; Eckardt, Kristin; Holen, Torgeir; Langleite, Torgrim Mikal; Lee, Sindre; Jensen, Jørgen; Birkeland, Kåre I.; Drevon, Christian A & Hjorth, Marit (2017). Global mRNA sequencing of human skeletal muscle: Search for novel exercise-regulated myokines. Molecular Metabolism.  ISSN 2212-8778.  6(4), s 352- 365 . doi: 10.1016/j.molmet.2017.01.007 Fulltekst i vitenarkiv. Vis sammendrag

  Objective: Skeletal muscle is an important secretory organ, producing and releasing numerous myokines, which may be involved in mediating beneficial health effects of physical activity. More than 100 myokines have been identified by different proteomics approaches, but these techniques may not detect all myokines. We used mRNA sequencing as an untargeted approach to study gene expression of secreted proteins in skeletal muscle upon acute as well as long-term exercise. Methods: Twenty-six middle-aged, sedentary men underwent combined endurance and strength training for 12 weeks. Skeletal muscle biopsies from m. vastus lateralis and blood samples were taken before and after an acute bicycle test, performed at baseline as well as after 12 weeks of training intervention. We identified transcripts encoding secretory proteins that were changed more than 1.5-fold in muscle after exercise. Secretory proteins were defined based on either curated UniProt annotations or predictions made by multiple bioinformatics methods. Results: This approach led to the identification of 161 candidate secretory transcripts that were up-regulated after acute exercise and 99 that where increased after 12 weeks exercise training. Furthermore, 92 secretory transcripts were decreased after acute and/or long-term physical activity. From these responsive transcripts, we selected 17 candidate myokines sensitive to short- and/or long-term exercise that have not been described as myokines before. The expression of these transcripts was confirmed in primary human skeletal muscle cells during in vitro differentiation and electrical pulse stimulation (EPS). One of the candidates we identified was macrophage colony-stimulating factor-1 (CSF1), which influences macrophage homeostasis. CSF1 mRNA increased in skeletal muscle after acute and long-term exercise, which was accompanied by a rise in circulating CSF1 protein. In cultured muscle cells, EPS promoted a significant increase in the expression and secretion of CSF1. Conclusion: We identified 17 new, exercise-responsive transcripts encoding secretory proteins. We further identified CSF1 as a novel myokine, which is secreted from cultured muscle cells and up-regulated in muscle and plasma after acute exercise.

• Pourteymour, Shirin; Hjorth, Marit; Lee-Ødegård, Sindre; Holen, Torgeir; Langleite, Torgrim Mikal; Jensen, Jørgen; Birkeland, Kåre I.; Drevon, Christian A & Eckardt, Kristin (2017). Dual specificity phosphatase 5 and 6 are oppositely regulated in human skeletal muscle by acute exercise. Physiological Reports.  ISSN 2051-817X.  5:e13459(19), s 1- 14 . doi: 10.14814/phy2.13459 Fulltekst i vitenarkiv.
• Görgens, Sven W.; Hjorth, Marit; Eckardt, Kristin; Wichert, Stefan; Norheim, Frode; Holen, Torgeir; Lee, Sindre; Langleite, Torgrim Mikal; Birkeland, Kåre I.; Stadheim, Hans Kristian; Kolnes, Kristoffer Jensen; Tangen, Daniel S.; Kolnes, Anders J.; Jensen, Jørgen; Drevon, Christian A & Eckel, Jürgen (2016). The exercise-regulated myokine chitinase-3-like protein 1 stimulates human myocyte proliferation. Acta Physiologica.  ISSN 1748-1708.  216(3), s 330- 345 . doi: 10.1111/apha.12579 Vis sammendrag

  Aim: Chitinase-3-like protein 1 (CHI3L1) is involved in tissue remodelling and inflammatory processes. Plasma levels are elevated in patients with insulin resistance and T2DM. We recently showed that CHI3L1 and its receptor protease-activated receptor 2 (PAR-2) are expressed in skeletal muscle. Activation of PAR-2 by CHI3L1 protects against TNF- a -induced inflammation and insulin resistance. However, the effect of exercise on CHI3L1 and PAR-2 signalling remains unknown. The aim of this work was to study the impact of exercise on CHI3L1 production and the effect of CHI3L1/PAR-2 signalling on skeletal muscle growth and repair. Methods: Three human exercise studies were used to measure CHI3L1 plasma levels ( n = 32). In addition, muscle and adipose tissue CHI3L1 mRNA expression was measured in response to acute and long-term exer- cise ( n = 24). Primary human skeletal muscle cells were differentiated in vitro, and electrical pulse stimulation was applied. In addition, myo- blasts were incubated with CHI3L1 protein and activation of MAP kinase signalling as well as proliferation was measured. Results: Circulating CHI3L1 levels and muscle CHI3L1 mRNA were increased after acute exercise. In addition, CHI3L1 mRNA expression as well as CHI3L1 secretion was enhanced in electrically stimulated cultured myotubes. Incubation of cultured human myoblasts with CHI3L1 protein leads to a strong activation of p44/42, p38 MAPK and Akt as well as enhanced myoblast proliferation. Conclusion: Our findings suggest that CHI3L1 is induced by acute exer- cise and that CHI3L1/PAR-2 signalling activates myocyte proliferation, which is important for restructuring of skeletal muscle in the response to exercise training.

• Hjorth, Marit; Pourteymour, Shirin; Goergens, S W; Langleite, Torgrim Mikal; Lee, Sindre; Holen, Torgeir; Gulseth, Hanne Løvdal; Birkeland, Kåre I.; Jensen, Jørgen; Drevon, Christian A & Norheim, Frode (2016). Myostatin in relation to physical activity and dysglycaemia and its effect on energy metabolism in human skeletal muscle cells. Acta Physiologica.  ISSN 1748-1708.  217(1), s 45- 60 . doi: 10.1111/apha.12631
• Langleite, Torgrim Mikal; Jensen, Jørgen; Norheim, Frode; Gulseth, Hanne Løvdal; Tangen, Daniel S.; Kolnes, Kristoffer Jensen; Heck, Ansgar; Storås, Tryggve; Lie, Guro Grøthe; Dahl, Marius; Kielland, Anders; Holen, Torgeir; NORENG, HANS JØRGEN; Stadheim, Hans Kristian; Bjørnerud, Atle; Johansen, Egil Ivar; Nellemann, Birgitte; Birkeland, Kåre I. & Drevon, Christian A (2016). Insulin sensitivity, body composition and adipose depots following 12 w combined endurance and strength training in dysglycemic and normoglycemic sedentary men. Archives of Physiology and Biochemistry.  ISSN 1381-3455.  122(4), s 167- 179 . doi: 10.1080/13813455.2016.1202985
• Lee, Sindre; Norheim, Frode; Langleite, Torgrim Mikal; NORENG, HANS JØRGEN; Storås, Tryggve; Afman, Lydia A.; Frost, Gary; Bell, Jimmy D.; Thomas, E. Louise; Kolnes, Kristoffer Jensen; Tangen, Daniel S.; Stadheim, Hans Kristian; Gilfillan, Gregor Duncan; Gulseth, Hanne Løvdal; Birkeland, Kåre I.; Jensen, Jørgen; Drevon, Christian A & Holen, Torgeir (2016). Effect of energy restriction and physical exercise intervention on phenotypic flexibility as examined by transcriptomics analyses of mRNA from adipose tissue and whole body magnetic resonance imaging. Physiological Reports.  ISSN 2051-817X.  4(21) . doi: 10.14814/phy2.13019 Vis sammendrag

  Overweight and obesity lead to changes in adipose tissue such as inflammation and reduced insulin sensitivity. The aim of this study was to assess how altered energy balance by reduced food intake or enhanced physical activity affect these processes. We studied sedentary subjects with overweight/obesity in two intervention studies, each lasting 12 weeks affecting energy balance either by energy restriction (~20% reduced intake of energy from food) in one group, or by enhanced energy expenditure due to physical exercise (combined endurance‐ and strength‐training) in the other group. We monitored mRNA expression by microarray and mRNA sequencing from adipose tissue biopsies. We also measured several plasma parameters as well as fat distribution with magnetic resonance imaging and spectroscopy. Comparison of microarray and mRNA sequencing showed strong correlations, which were also confirmed using RT‐PCR. In the energy restricted subjects (body weight reduced by 5% during a 12 weeks intervention), there were clear signs of enhanced lipolysis as monitored by mRNA in adipose tissue as well as plasma concentration of free‐fatty acids. This increase was strongly related to increased expression of markers for M1‐like macrophages in adipose tissue. In the exercising subjects (glucose infusion rate increased by 29% during a 12‐week intervention), there was a marked reduction in the expression of markers of M2‐like macrophages and T cells, suggesting that physical exercise was especially important for reducing inflammation in adipose tissue with insignificant reduction in total body weight. Our data indicate that energy restriction and physical exercise affect energy‐related pathways as well as inflammatory processes in different ways, probably related to macrophages in adipose tissue.

• Hjorth, Marit; Norheim, Frode; Meen, Astri Jeanette; Pourteymour, Shirin; Lee, Sindre; Holen, Torgeir; Jensen, Jørgen; Birkeland, Kåre I.; Martinov, Vladimir Nikolkaev; Langleite, Torgrim Mikal; Eckardt, Kristin; Drevon, Christian A & Kolset, Svein Olav (2015). The effect of acute and long-term physical activity on extracelluar Matrix and serglycin in huuman skeletal muscle. Physiological Reports.  ISSN 2051-817X.  3:e12473(8), s 1- 19 . doi: 10.14814/phy2.12473
• Pourteymour, Shirin; Lee, Sindre; Langleite, Torgrim Mikal; Eckardt, Kristin; Hjorth, Marit; Bindesbøll, Christian; Dalen, Knut Tomas; Birkeland, Kåre I.; Drevon, Christian A; Holen, Torgeir & Norheim, Frode (2015). Perilipin 4 in human skeletal muscle: localization and effect of physical activity. Physiological Reports.  ISSN 2051-817X.  3:e12481(8), s 1- 15 . doi: 10.14814/phy2.12481
• Li, Yuchuan; Lee, Sindre; Langleite, Torgrim Mikal; Norheim, Frode; Pourteymour, Shirin; Jensen, Jørgen; Stadheim, Hans Kristian; Storås, Tryggve; Davanger, Svend; Gulseth, Hanne Løvdal; Birkeland, Kåre I.; Drevon, Christian A & Holen, Torgeir (2014). Subsarcolemmal lipid droplet responses to a combined endurance and strength exercise intervention. Physiological Reports.  ISSN 2051-817X.  2(11) . doi: 10.14814/phy2.12187
• Norheim, Frode; Hjorth, Marit; Langleite, Torgrim Mikal; Lee, Sindre; Holen, Torgeir; Bindesbøll, Christian; Stadheim, Hans Kristian; Gulseth, Hanne Lovdal; Birkeland, Kåre I.; Kielland, Anders; Jensen, Jørgen; Dalen, Knut Tomas & Drevon, Christian A (2014). Regulation of angiopoietin-like protein 4 Production during and after exercise. Physiological Reports.  ISSN 2051-817X.  2(8) . doi: 10.14814/phy2.12109
• Norheim, Frode; Langleite, Torgrim Mikal; Hjorth, Marit; Holen, Torgeir; Kielland, Anders; Stadheim, Hans Kristian; Gulseth, Hanne Løvdal; Birkeland, Kåre I.; Jensen, Jørgen & Drevon, Christian A (2014). The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. The FEBS Journal.  ISSN 1742-464X.  281(3), s 739- 749 . doi: 10.1111/febs.12619 Vis sammendrag

  Irisin was first identified as a peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α) dependent myokine with the potential to induce murine brown-fat-like development of white adipose tissue. In humans, the regulatory effect of training on muscle FNDC5mRNA expression and subsequently irisin levels in plasma is more controversial. We recruited 26 inactive men (13 normoglycaemic and normal weight, controls; and 13 slightly hyperglycaemic and overweight, pre-diabetes group) aged 40–65 years for a 12-week intervention of combined endurance and strength training with four sessions of training per week. Before and after the 12-week intervention period, participants were exposed to an acute endurance workload of 45 min at 70% of VO2max, and muscle biopsies were taken prior to and after exercise. Skeletal muscle mRNA for PGC1A and FNDC5 correlated and both PGC1A and FNDC5mRNA levels increased after 12 weeks of training in both control and pre-diabetes subjects. Circulating irisin was reduced in response to 12 weeks of training, and was increased acutely (~1.2-fold) just after acute exercise. Plasma concentration of irisin was higher in pre-diabetes subjects compared with controls. There was little effect of 12 weeks of training on selected browning genes in subcutaneous adipose tissue. UCP1mRNA did not correlate with FNDC5 expression in subcutaneous adipose tissue or skeletal muscle or with irisin levels in plasma. We observed no enhancing effect of long-term training on circulating irisin levels, and little or no effect of training on browning of subcutaneous white adipose tissue in humans.

• Gutzkow, Kristine Bjerve; Langleite, Torgrim Mikal; Meier, Silja; Graupner, Anne; Collins, Andrew Richard & Brunborg, Gunnar (2013). High-throughput comet assay using 96 minigels. Mutagenesis.  ISSN 0267-8357.  28(3), s 333- 340 . doi: 10.1093/mutage/get012
• Norheim, Frode; Gjelstad, Ingrid Merethe Fange; Hjorth, Marit; Vinknes, Kathrine; Langleite, Torgrim Mikal; Holen, Torgeir; Jensen, Jørgen; Dalen, Knut Tomas; Karlsen, Anette; Kielland, Anders; Rustan, Arild & Drevon, Christian A (2012). Molecular nutrition research - the modern way of performing nutritional science. Nutrients.  ISSN 2072-6643.  4(12), s 1898- 1944 . doi: 10.3390/nu4121898 Vis sammendrag

  In spite of amazing progress in food supply and nutritional science, and a striking increase in life expectancy of approximately 2.5 months per year in many countries during the previous 150 years, modern nutritional research has a great potential of still contributing to improved health for future generations, granted that the revolutions in molecular and systems technologies are applied to nutritional questions. Descriptive and mechanistic studies using state of the art epidemiology, food intake registration, genomics with single nucleotide polymorphisms (SNPs) and epigenomics, transcriptomics, proteomics, metabolomics, advanced biostatistics, imaging, calorimetry, cell biology, challenge tests (meals, exercise, etc.), and integration of all data by systems biology, will provide insight on a much higher level than today in a field we may name molecular nutrition research. To take advantage of all the new technologies scientists should develop international collaboration and gather data in large open access databases like the suggested Nutritional Phenotype database (dbNP). This collaboration will promote standardization of procedures (SOP), and provide a possibility to use collected data in future research projects. The ultimate goals of future nutritional research are to understand the detailed mechanisms of action for how nutrients/foods interact with the body and thereby enhance health and treat diet-related diseases.

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• Eckardt, Kristin; Pourteymour, Shirin; Hjorth, Marit; Lee, Sindre; Langleite, Torgrim Mikal; Holen, Torgeir; Jensen, Jørgen; Birkeland, Kåre I. & Drevon, Christian A (2016). Dual specificity phosphatase 5 and 6 are oppositely regulated in human skeletal muscle by acute exercise.
• Eckardt, Kristin; Lee, Sindre; Langleite, Torgrim Mikal; Holen, Torgeir; Jensen, Jørgen; Birkeland, Kåre I. & Drevon, Christian A (2015). Stearoyl-CoA desaturase and its regulation in human skeletal muscle by exercise.
• Kase, Eili Tranheim; Lund, Jenny; Feng, Yuan Zeng; Langleite, Torgrim Mikal; Aas, Vigdis; Jensen, Jan S.; Birkeland, Kåre I.; Gulseth, Hanne Løvdal; Drevon, Christian A; Rustan, Arild & Thoresen, G. Hege (2013). Effect of exercise on fatty acid and glucose metabolism in cultured human myotubes. Diabetologia.  ISSN 0012-186X.  56, s S250- S250

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