Marit Hjorth

• Viken, Jonas Krag; Olsen, Thomas; Drevon, Christian André; Hjorth, Marit; Birkeland, Kåre Inge & Norheim, Frode Amador [Vis alle 7 forfattere av denne artikkelen] (2024). Intra-Individual Variations in How Insulin Sensitivity Responds to Long-Term Exercise: Predictions by Machine Learning Based on Large-Scale Serum Proteomics. Metabolites. ISSN 2218-1989. doi: 10.3390/metabo14060335.
• Nolsøe, Jens Mortansson Jelstrup; Underhaug, Jarl; Sørskår, Åshild Moi; Antonsen, Simen; Malterud, Karl Egil & Gani, Osman [Vis alle 11 forfattere av denne artikkelen] (2024). Biological Evaluations, NMR Analyses, Molecular Modeling Studies, and Overview of the Synthesis of the Marine Natural Product (−)-Mucosin . Molecules. ISSN 1431-5157. 29(5). doi: 10.3390/molecules29050994. Fulltekst i vitenarkiv Vis sammendrag

  Natural products obtained from marine organisms continue to be a rich source of novel structural architecture and of importance in drug discovery, medicine, and health. However, the success of such endeavors depends on the exact structural elucidation and access to sufficient material, often by stereoselective total synthesis, of the isolated natural product of interest. (−)-Mucosin (1), a fatty acid derivative, previously presumed to contain a rare cis-bicyclo[4.3.0]non-3-ene moiety, has since been shown to be the trans-congener. Analytically, the fused bicyclic ring system in (−)-1 constitutes a particular challenge in order to establish its relative and absolute stereochemistry. Herein, data from biological evaluations, NMR and molecular modeling studies of (−)-1 are presented. An overview of the synthetic strategies enabling the exact structural elucidation of (−)-mucosin (1) is also presented.

• Doncheva, Atanaska Ivanova; Li, Yuchuan; Khanal, Prabhat; Hjorth, Marit; Kolset, Svein Olav & Norheim, Frode Amador [Vis alle 8 forfattere av denne artikkelen] (2023). Altered hepatic lipid droplet morphology and lipid metabolism in fasted Plin2-null mice. Journal of Lipid Research. ISSN 0022-2275. 64(12). doi: 10.1016/j.jlr.2023.100461. Fulltekst i vitenarkiv
• Hjorth, Marit; Doncheva, Atanaska Ivanova; Norheim, Frode Amador; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Sæther, Thomas [Vis alle 7 forfattere av denne artikkelen] (2022). Consumption of salmon fishmeal increases hepatic cholesterol content in obese C57BL/6 J mice. European Journal of Nutrition. ISSN 1436-6207. 61, s. 4027–4043. doi: 10.1007/s00394-022-02930-y. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Purpose By-products from farmed fish contain large amounts of proteins and may be used for human consumption. The purpose of this study was to investigate cardiometabolic effects and metabolic tolerance in mice consuming fishmeal from salmon by-products, salmon filet or beef. Methods Female C57BL/6J mice were fed chow, as a healthy reference group, or a high-fat diet for 10 weeks to induce obesity and glucose intolerance. Obese mice were subsequently given isocaloric diets containing 50% of the dietary protein from salmon fishmeal, salmon filet or beef for 10 weeks. Mice were subjected to metabolic phenotyping, which included measurements of body composition, energy metabolism in metabolic cages and glucose tolerance. Lipid content and markers of hepatic toxicity were determined in plasma and liver. Hepatic gene and protein expression was determined with RNA sequencing and immunoblotting. Results Mice fed fishmeal, salmon filet or beef had similar food intake, energy consumption, body weight gain, adiposity, glucose tolerance and circulating levels of lipids and hepatic toxicity markers, such as p-ALT and p-AST. Fishmeal increased hepatic cholesterol levels by 35–36% as compared to salmon filet (p = 0.0001) and beef (p = 0.005). This was accompanied by repressed expression of genes involved in steroid and cholesterol metabolism and reduced levels of circulating Pcsk9. Conclusion Salmon fishmeal was well tolerated, but increased hepatic cholesterol content. The high cholesterol content in fishmeal may be responsible for the effects on hepatic cholesterol metabolism. Before introducing fishmeal from salmon by-products as a dietary component, it may be advantageous to reduce the cholesterol content in fishmeal. Introduction

• Doncheva, Atanaska Ivanova; Romero, Silvana Angelica Troncoso; Ramirez-Garrastacho, Manuel; Lee-Ødegård, Sindre; Kolnes, Kristoffer Jensen & Tangen, Daniel S. [Vis alle 11 forfattere av denne artikkelen] (2022). Extracellular vesicles and microRNAs are altered in response to exercise, insulin sensitivity and overweight. Acta Physiologica. ISSN 1748-1708. 236(4). doi: 10.1111/apha.13862. Fulltekst i vitenarkiv
• Torp, May-Kristin; Ranheim, Trine; Schjalm, Camilla; Hjorth, Marit; Heiestad, Christina Mathisen & Dalen, Knut Tomas [Vis alle 13 forfattere av denne artikkelen] (2022). Intracellular Complement Component 3 Attenuated Ischemia-Reperfusion Injury in the Isolated Buffer-Perfused Mouse Heart and Is Associated With Improved Metabolic Homeostasis. Frontiers in Immunology. ISSN 1664-3224. 13. doi: 10.3389/fimmu.2022.870811. Fulltekst i vitenarkiv Vis sammendrag

  The innate immune system is rapidly activated during myocardial infarction and blockade of extracellular complement system reduces infarct size. Intracellular complement, however, appears to be closely linked to metabolic pathways and its role in ischemia-reperfusion injury is unknown and may be different from complement activation in the circulation. The purpose of the present study was to investigate the role of intracellular complement in isolated, retrogradely buffer-perfused hearts and cardiac cells from adult male wild type mice (WT) and from adult male mice with knockout of complement component 3 (C3KO). Main findings: (i) Intracellular C3 protein was expressed in isolated cardiomyocytes and in whole hearts, (ii) after ischemia-reperfusion injury, C3KO hearts had larger infarct size (32 ± 9% in C3KO vs. 22 ± 7% in WT; p=0.008) and impaired post-ischemic relaxation compared to WT hearts, (iii) C3KO cardiomyocytes had lower basal oxidative respiration compared to WT cardiomyocytes, (iv) blocking mTOR decreased Akt phosphorylation in WT, but not in C3KO cardiomyocytes, (v) after ischemia, WT hearts had higher levels of ATP, but lower levels of both reduced and oxidized nicotinamide adenine dinucleotide (NADH and NAD+, respectively) compared to C3KO hearts. Conclusion: intracellular C3 protected the heart against ischemia-reperfusion injury, possibly due to its role in metabolic pathways important for energy production and cell survival.

• Hjorth, Marit; Galigniana, Natalia; Ween, Ola; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Dalen, Knut Tomas [Vis alle 7 forfattere av denne artikkelen] (2022). Postprandial Effects of Salmon Fishmeal and Whey on Metabolic Markers in Serum and Gene Expression in Liver Cells. Nutrients. ISSN 2072-6643. 14(8). doi: 10.3390/nu14081593. Fulltekst i vitenarkiv Vis sammendrag

  Fish is considered an important part of a healthy diet, in part due to the content of long chain omega-3 fatty acids. However, both lean and fatty fish have beneficial health effects, suggesting that micronutrients and proteins may play a role. In a randomised, controlled, cross-over trial, five healthy male participants consumed 5.2 g of protein from either salmon fishmeal or whey. Blood samples were taken before and 30 and 60 min after intake. The concentration of glucose, lipids, hormones and metabolites, including 28 different amino acids and derivatives, were measured in serum or plasma. Cultured HepG2 cells were incubated with or without serum from the participants, and transcriptomic profiling was performed using RNA sequencing. The ingestion of both salmon fishmeal and whey reduced the glucose and triglyceride levels in serum. Protein intake, independent of the source, increased the concentration of 22 amino acids and derivatives in serum. Fishmeal increased the concentration of arginine, methionine, serine, glycine, cystathionine and 2-aminobutyric acid more than whey did. Incubation with postprandial serum resulted in large transcriptomic alterations in serum-fasted HepG2 cells, with the differential expression of >4500 protein coding genes. However, when comparing cells cultivated in fasting serum to postprandial serum after the ingestion of fishmeal and whey, we did not detect any differentially regulated genes, neither with respect to the protein source nor with respect to the time after the meal. The comparable nutrigenomic effects of fishmeal and whey do not change the relevance of fish by-products as an alternative food source.

• Hustad, Kristin Solheim; Ottestad, Inger Olaug; Hjorth, Marit; Dalen, Knut Tomas; Sæther, Thomas & Sheikh, Navida Akhter [Vis alle 9 forfattere av denne artikkelen] (2021). No effect of salmon fish protein on 2-h glucose in adults with increased risk of type 2 diabetes: a randomised controlled trial. British Journal of Nutrition. ISSN 0007-1145. 126(9), s. 1304–1313. doi: 10.1017/S0007114521000040. Fulltekst i vitenarkiv
• Doncheva, Atanaska Ivanova; Norheim, Frode Amador; Hjorth, Marit; Grujic, Mirjana; Paivandy, Aida & Dankel, Simon N [Vis alle 14 forfattere av denne artikkelen] (2021). Serglycin Is Involved in Adipose Tissue Inflammation in Obesity. Journal of Immunology. ISSN 0022-1767. 208(1), s. 121–132. doi: 10.4049/jimmunol.2100231. Vis sammendrag

  Chronic local inflammation of adipose tissue is an important feature of obesity. Serglycin is a proteoglycan highly expressed by various immune cell types known to infiltrate adipose tissue under obese conditions. To investigate if serglycin expression has an impact on diet-induced adipose tissue inflammation, we subjected Srgn+/+ and Srgn−/− mice (C57BL/6J genetic background) to an 8-wk high-fat and high-sucrose diet. The total body weight was the same in Srgn+/+ and Srgn−/− mice after diet treatment. Expression of white adipose tissue genes linked to inflammatory pathways were lower in Srgn−/− mice. We also noted reduced total macrophage abundance, a reduced proportion of proinflammatory M1 macrophages, and reduced formation of crown-like structures in adipose tissue of Srgn−/− compared with Srgn+/+ mice. Further, Srgn−/− mice had more medium-sized adipocytes and fewer large adipocytes. Differentiation of preadipocytes into adipocytes (3T3-L1) was accompanied by reduced Srgn mRNA expression. In line with this, analysis of single-cell RNA sequencing data from mouse and human adipose tissue supports that Srgn mRNA is predominantly expressed by various immune cells, with low expression in adipocytes. Srgn mRNA expression was higher in obese compared with lean humans and mice, accompanied by an increased expression of immune cell gene markers. SRGN and inflammatory marker mRNA expression was reduced upon substantial weight loss in patients after bariatric surgery. Taken together, this study introduces a role for serglycin in the regulation of obesity-induced adipose inflammation.

• Li, Yuchuan; Khanal, Prabhat; Norheim, Frode; Hjorth, Marit; Bjellaas, Thomas & Drevon, Christian A [Vis alle 9 forfattere av denne artikkelen] (2021). Plin2 deletion increases cholesteryl ester lipid droplet content and disturbs cholesterol balance in adrenal cortex. Journal of Lipid Research. ISSN 0022-2275. 62. doi: 10.1016/J.JLR.2021.100048. Fulltekst i vitenarkiv
• Olsen, Thomas; Øvrebø, Bente; Haj Yasein, Nadia; Lee-Ødegård, Sindre; Svendsen, Karianne & Hjorth, Marit [Vis alle 11 forfattere av denne artikkelen] (2020). Effects of dietary methionine and cysteine restriction on plasma biomarkers, serum fibroblast growth factor 21, and adipose tissue gene expression in women with overweight or obesity: a double-blind randomized controlled pilot study. Journal of Translational Medicine. ISSN 1479-5876. 18(122). doi: 10.1186/s12967-020-02288-x. Fulltekst i vitenarkiv
• Whitham, Martin; Pal, Martin; Petzold, Tim; Hjorth, Marit; Egan, Casey L & Brunner, Julia S [Vis alle 14 forfattere av denne artikkelen] (2019). Adipocyte-specific deletion of IL-6 does not attenuate obesity-induced weight gain or glucose intolerance in mice. American Journal of Physiology. Endocrinology and Metabolism. ISSN 0193-1849. 317(4), s. E597–E604. doi: 10.1152/ajpendo.00206.2019.
• Whitham, Martin; Parker, Benjamin L; Friedrichsen, Martin; Hingst, Janne R; Hjorth, Marit & Hughes, William E [Vis alle 20 forfattere av denne artikkelen] (2018). Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise. Cell Metabolism. ISSN 1550-4131. 27(1), s. 237–251. doi: 10.1016/j.cmet.2017.12.001.
• Reibe, Saskia; Hjorth, Marit; Febbraio, Mark A & Whitham, Martin (2018). GeneXX: an online tool for the exploration of transcript changes in skeletal muscle associated with exercise. Physiological Genomics. ISSN 1094-8341. 50(5), s. 376–384. doi: 10.1152/physiolgenomics.00127.2017.
• Pourteymour, Shirin; Hjorth, Marit; Lee-Ødegård, Sindre; Holen, Torgeir; Langleite, Torgrim Mikal & Jensen, Jørgen [Vis alle 9 forfattere av denne artikkelen] (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
• Pourteymour, Shirin; Eckardt, Kristin; Holen, Torgeir; Langleite, Torgrim Mikal; Lee, Sindre & Jensen, Jørgen [Vis alle 9 forfattere av denne artikkelen] (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.

• Hjorth, Marit; Pourteymour, Shirin; Goergens, S W; Langleite, Torgrim Mikal; Lee, Sindre & Holen, Torgeir [Vis alle 11 forfattere av denne artikkelen] (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.
• Görgens, Sven W.; Hjorth, Marit; Eckardt, Kristin; Wichert, Stefan; Norheim, Frode & Holen, Torgeir [Vis alle 16 forfattere av denne artikkelen] (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.

• Pourteymour, Shirin; Lee, Sindre; Langleite, Torgrim Mikal; Eckardt, Kristin; Hjorth, Marit & Bindesbøll, Christian [Vis alle 11 forfattere av denne artikkelen] (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.
• Hjorth, Marit; Norheim, Frode; Meen, Astri Jeanette; Pourteymour, Shirin; Lee, Sindre & Holen, Torgeir [Vis alle 13 forfattere av denne artikkelen] (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.
• Norheim, Frode; Hjorth, Marit; Langleite, Torgrim Mikal; Lee, Sindre; Holen, Torgeir & Bindesbøll, Christian [Vis alle 13 forfattere av denne artikkelen] (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 [Vis alle 10 forfattere av denne artikkelen] (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.

• Norheim, Frode; Gjelstad, Ingrid Merethe Fange; Hjorth, Marit; Vinknes, Kathrine; Langleite, Torgrim Mikal & Holen, Torgeir [Vis alle 12 forfattere av denne artikkelen] (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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• Hjorth, Marit; Doncheva, Atanaska Ivanova; Norheim, Frode Amador; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Sæther, Thomas [Vis alle 7 forfattere av denne artikkelen] (2022). Consumption of salmon fishmeal increases hepatic cholesterol content in obese C57BL/6J mice .
• Holven, Kirsten Bjørklund; Sæther, Thomas; Hjorth, Marit; Dalen, Knut Tomas; Ulven, Stine Marie & Ottestad, Inger [Vis alle 7 forfattere av denne artikkelen] (2019). Kan fisk utnyttes enda mer og samtidig fremme folkehelsen? Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. 17(2), s. 20–22.
• Hjorth, Marit & Febbraio, Mark A (2018). Exercise as medicine for survivors of paediatric cancer. Nature Reviews Endocrinology. ISSN 1759-5029. 14(9), s. 506–508. doi: 10.1038/s41574-018-0065-6.
• Hjorth, Marit & Febbraio, Mark A (2017). IL-1β delivers a sweet deal. Nature Immunology. ISSN 1529-2908. 18(3), s. 247–248. doi: 10.1038/ni.3681.
• Eckardt, Kristin; Pourteymour, Shirin; Hjorth, Marit; Lee, Sindre; Langleite, Torgrim Mikal & Holen, Torgeir [Vis alle 9 forfattere av denne artikkelen] (2016). Dual specificity phosphatase 5 and 6 are oppositely regulated in human skeletal muscle by acute exercise.

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