Camilla Collin Hansen
Verified @nexs.ku.dk
Faculty of Science
University of Copenhagen
Scopus Publications
Scopus Publications
Arthur Ingersen, Hildegunn Rømma Helset, Monika Calov, Elizaveta Chabanova, Eva Gjerlevsen Harreskov, Christina Jensen, Christina Neigaard Hansen, Clara Prats, Jørn Wulff Helge, Steen Larsen,et al.
Frontiers Media SA
Alternate-day fasting induces oscillations in energy stores. We hypothesized that repeated oscillations increases insulin secretion and sensitivity, and improve metabolic health in patients with obesity with or without type 2 diabetes (T2DM). Twenty-three male patients fasted every other day for 30 h for 6 weeks. Experiments included resting energy expenditure, continuous glucose monitoring, intravenous glucose tolerance test, euglycemic hyperinsulinemic clamp, body composition, hepatic triglyceride content, muscle biopsies which were performed at baseline, during 3 weeks without allowed weight loss, and after additional 3 weeks with weight loss. Bodyweight decreased ∼1% and further ∼3% during weeks one to three and four to six, respectively (p < 0.05). Only minor changes in fat mass occurred in weeks 1–3. With weight loss, visceral fat content decreased by 13 ± 3% and 12 ± 2% from baseline in patients with and without T2DM, respectively (p < 0.05). Hepatic triglyceride content decreased by 17 ± 9% and 36 ± 9% (with diabetes) and 27 ± 8% and 40 ± 8% (without diabetes) from baseline to week 3 and week 6, respectively (all p < 0.05). Muscle lipid and glycogen content oscillated with the intervention. Glucose homeostasis, insulin secretion and sensitivity was impaired in patients with T2DM and did not change without weight loss, but improved (p < 0.05) when alternate day fasting was combined with weight loss. In conclusion, alternate-day fasting is feasible in patients with obesity and T2DM, and decreases visceral fat and liver fat deposits. Energy store oscillations by alternate-day fasting do not improve insulin secretion or sensitivity per se.Clinical Trial registration: (ClinicalTrials.gov), (ID NCT02420054).
Solvejg L. Hansen, Kirstine N. Bojsen-Møller, Anne-Marie Lundsgaard, Frederikke L. Hendrich, Lisbeth Nilas, Kim A. Sjøberg, Janne R. Hingst, Annette K. Serup, Carlos Henríquez Olguín, Christian S. Carl,et al.
American Diabetes Association
Women with polycystic ovary syndrome (PCOS) have been shown to be less insulin sensitive compared with control (CON) women, independent of BMI. Training is associated with molecular adaptations in skeletal muscle, improving glucose uptake and metabolism in both healthy individuals and patients with type 2 diabetes. In the current study, lean hyperandrogenic women with PCOS (n = 9) and healthy CON women (n = 9) completed 14 weeks of controlled and supervised exercise training. In CON, the training intervention increased whole-body insulin action by 26% and insulin-stimulated leg glucose uptake by 53% together with increased insulin-stimulated leg blood flow and a more oxidative muscle fiber type distribution. In PCOS, no such changes were found, despite similar training intensity and improvements in VO2max. In skeletal muscle of CON but not PCOS, training increased GLUT4 and HKII mRNA and protein expressions. These data suggest that the impaired increase in whole-body insulin action in women with PCOS with training is caused by an impaired ability to upregulate key glucose-handling proteins for insulin-stimulated glucose uptake in skeletal muscle and insulin-stimulated leg blood flow. Still, other important benefits of exercise training appeared in women with PCOS, including an improvement of the hyperandrogenic state.
Flemming Dela, Arthur Ingersen, Nynne B. Andersen, Maria B. Nielsen, Helga H. H. Petersen, Christina N. Hansen, Steen Larsen, Jørgen Wojtaszewski, and Jørn Wulff Helge
Wiley
To examine the effect of high‐intensity interval training (HIIT) on glucose clearance rates in skeletal muscle and explore the mechanism within the muscle.
M. D. Kristensen, S. M. Petersen, K. E. Møller, M. T. Lund, M. Hansen, C. N Hansen, J. Courraud, J. W. Helge, F. Dela, and C. Prats
Wiley
Skeletal muscle lipid stores and mitochondrial function have been appointed as key players in obesity‐induced insulin resistance. However, there are conflicting reports in the literature based on in vitro quantitative measurements. Here, we test the hypothesis that it is not the quantity but the quality that matters.
C K Hansen, L Klingenberg, L B Larsen, J K Lorenzen, K V Sørensen, and A Astrup
Springer Science and Business Media LLC
Malene M. Kristensen, Peter K. Davidsen, Andreas Vigelsø, Christina N. Hansen, Lars J. Jensen, Niels Jessen, Jens M. Bruun, Flemming Dela, and Jørn W. Helge
Wiley
Obesity is central in the development of insulin resistance. However, the underlying mechanisms still need elucidation. Dysregulated microRNAs (miRNAs; post‐transcriptional regulators) in adipose tissue may present an important link.
Andreas Vigelsø, Martin Gram, Caroline Wiuff, Christina Neigaard Hansen, Clara Prats, Flemming Dela, and Jørn Wulff Helge
Springer Science and Business Media LLC
Martin Hey-Mogensen, Martin Gram, Martin Borch Jensen, Michael Taulo Lund, Christina Neigaard Hansen, Morten Scheibye-Knudsen, Vilhelm A. Bohr, and Flemming Dela
Wiley
The present study utilized a novel method aiming to investigate mitochondrial function in human skeletal muscle at submaximal levels and at a predefined membrane potential. The effect of age and training status was investigated using a cross‐sectional design. Ageing was found to be related to decreased leak regardless of training status. Increased training status was associated with increased mitochondrial hydrogen peroxide emission.
M. Kristensen, B. Pötzelsberger, P. Scheiber, A. Bergdahl, C. N. Hansen, J. L. Andersen, M. Narici, S. Salvioli, M. Conte, E. Müller,et al.
Wiley
We investigated the effect of alpine skiing for 12 weeks on skeletal muscle characteristics and biomarkers of glucose homeostasis and cardiovascular risk factors. Twenty‐three patients with a total knee arthroplasty (TKA) were studied 2.9 ± 0.9 years (mean ± SD) after the operation. Fourteen patients participated in the intervention group (IG) and nine in the control group (CG). Blood samples and muscle biopsies were obtained before (PRE) and 7.3 ± 0.8 days after (POST) the intervention, and blood samples again after a retention (RET) phase of 8 weeks. With skiing, glucose homeostasis improved in IG (decrease in fasting insulin, increase in muscle glycogen) but not in CG. Fiber type distribution and size, as well as capillary density and number of capillaries around the fibers (CAF), were not different between the operated and the non‐operated leg in either group. The relative number of type I fibers increased with skiing in IG with no change in CG. Inflammatory biomarkers, plasma lipids, and mitochondrial proteins and activity did not change. Alpine skiing is metabolically beneficial and can be used as a training modality by elderly people with TKA.
Liselotte B. Christiansen, Flemming Dela, Jørgen Koch, Christina N. Hansen, Pall S. Leifsson, and Takashi Yokota
American Physiological Society
Mitochondrial dysfunction and oxidative stress are important players in the development of various cardiovascular diseases, but their roles in hypertrophic cardiomyopathy (HCM) remain unknown. We examined whether mitochondrial oxidative phosphorylation (OXPHOS) capacity was impaired with enhanced mitochondrial oxidative stress in HCM. Cardiac and skeletal muscles were obtained from 9 domestic cats with spontaneously occurring HCM with preserved left ventricular systolic function and from 15 age-matched control cats. Mitochondrial OXPHOS capacities with nonfatty acid and fatty acid substrates in permeabilized fibers and isolated mitochondria were assessed using high-resolution respirometry. ROS release originating from isolated mitochondria was assessed by spectrofluorometry. Thiobarbituric acid-reactive substances were also measured as a marker of oxidative damage. Mitochondrial ADP-stimulated state 3 respiration with complex I-linked nonfatty acid substrates and with fatty acid substrates, respectively, was significantly lower in the hearts of HCM cats compared with control cats. Mitochondrial ROS release during state 3 with complex I-linked substrates and thiobarbituric acid-reactive substances in the heart were significantly increased in cats with HCM. In contrast, there were no significant differences in mitochondrial OXPHOS capacity, mitochondrial ROS release, and oxidative damage in skeletal muscle between groups. Mitochondrial OXPHOS capacity with both nonfatty acid substrates and fatty acid substrates was impaired with increased mitochondrial ROS release in the feline HCM heart. These findings provide new insights into the pathophysiology of HCM and support the hypothesis that restoration of the redox state in the mitochondria is beneficial in the treatment of HCM.
Andreas Vigelsø, Rie Dybboe, Christina Neigaard Hansen, Flemming Dela, Jørn W. Helge, and Amelia Guadalupe Grau
American Physiological Society
Reference proteins (RP) or the total protein (TP) loaded is used to correct for uneven loading and/or transfer in Western blotting. However, the signal sensitivity and the influence of physiological conditions may question the normalization methods. Therefore, three widely used reference proteins [β-actin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and α-tubulin], as well as TP loaded measured by Stain-Free technology (SF) as normalization tool were tested. This was done using skeletal muscle samples from men subjected to physiological conditions often investigated in applied physiology where the intervention has been suggested to impede normalization (ageing, muscle atrophy, and different muscle fiber type composition). The linearity of signal and the methodological variation coefficient was obtained. Furthermore, the inter- and intraindividual variation in signals obtained from SF and RP was measured in relation to ageing, muscle atrophy, and different muscle fiber type composition, respectively. A stronger linearity of SF and β-actin compared with GAPDH and α-tubulin was observed. The methodological variation was relatively low in all four methods (4–11%). Protein level of β-actin and GAPDH was lower in older men compared with young men. In conclusion, β-actin, GAPDH, and α-tubulin may not be used for normalization in studies that include subjects with a large age difference. In contrast, the RPs may not be affected in studies that include muscle wasting and differences in muscle fiber type. The novel SF technology adds lower variation to the results compared with the existing methods for correcting for loading inaccuracy in Western blotting of human skeletal muscle in applied physiology.
Martin Gram, Andreas Vigelsø, Takashi Yokota, Christina Neigaard Hansen, Jørn Wulff Helge, Martin Hey-Mogensen, and Flemming Dela
Elsevier BV
Steen Larsen, Christina N. Hansen, Jørn W. Helge, and Flemming Dela
Elsevier BV
Nis Stride, Steen Larsen, Martin Hey-Mogensen, Christina N. Hansen, Clara Prats, Daniel Steinbrüchel, Lars Køber, and Flemming Dela
American Physiological Society
Chronic ischemic heart disease is associated with myocardial hypoperfusion. The resulting hypoxia potentially inflicts damage upon the mitochondria, leading to a compromised energetic state. Furthermore, ischemic damage may cause excessive production of reactive oxygen species (ROS), producing mitochondrial damage, hereby reinforcing a vicious circle. Ischemic preconditioning has been proven protective in acute ischemia, but the subject of chronic ischemic preconditioning has not been explored in humans. We hypothesized that mitochondrial respiratory capacity would be diminished in chronic ischemic regions of human myocardium but that these mitochondria would be more resistant to ex vivo ischemia and, second, that ROS generation would be higher in ischemic myocardium. The aim of this study was to test mitochondrial respiratory capacity during hyperoxia and hypoxia, to investigate ROS production, and finally to assess myocardial antioxidant levels. Mitochondrial respiration in biopsies from ischemic and nonischemic regions from the left ventricle of the same heart was compared in nine human subjects. Maximal oxidative phosphorylation capacity in fresh muscle fibers was lower in ischemic compared with nonischemic myocardium ( P < 0.05), but the degree of coupling (respiratory control ratio) did not differ ( P > 0.05). The presence of ex vivo hypoxia did not reveal any chronic ischemic preconditioning of the ischemic myocardial regions ( P > 0.05). ROS production was higher in ischemic myocardium ( P < 0.05), and the levels of antioxidant protein expression was lower. Diminished mitochondrial respiration capacity and excessive ROS production demonstrate an impaired mitochondrial function in ischemic human heart muscle. No chronic ischemic preconditioning effect was found.
Steen Larsen, Nis Stride, Martin Hey-Mogensen, Christina N. Hansen, Lia E. Bang, Henning Bundgaard, Lars B. Nielsen, Jørn W. Helge, and Flemming Dela
Elsevier BV
Steen Larsen, Nis Stride, Martin Hey-Mogensen, Christina N. Hansen, Lia E. Bang, Henning Bundgaard, Lars B. Nielsen, Jørn W. Helge, and Flemming Dela
Elsevier BV
M. Friedrichsen, R. Ribel-Madsen, B. Mortensen, C. N. Hansen, A. C. Alibegovic, L. Hojbjerre, M. P. Sonne, J. F. P. Wojtaszewski, B. Stallknecht, F. Dela,et al.
Bioscientifica
OBJECTIVE
The molecular mechanisms linking physical inactivity and muscle insulin resistance in humans have been suggested to include increased muscle inflammation, possibly associated with impaired oxidative metabolism. We employed a human bed rest study including 20 young males with normal birth weight (NBW) and 20 with low birth weight (LBW) and increased risk of diabetes.
METHODOLOGY
The subjects were studied before and after 9 days of bed rest using the euglycemic-hyperinsulinemic clamp and muscle biopsy excision. Muscle inflammatory status was assessed as nuclear factor-κB (NF-κB) activity and mRNA expression of the pro-inflammatory MCP1 (CCL2) and IL6 and the macrophage marker CD68. Furthermore, mRNA expression of genes central to oxidative phosphorylation (OXPHOS) was measured including ATP5O, COX7A1, NDUFB6, and UQCRB.
RESULTS
At baseline, muscle inflammatory status was similar in NBW and LBW individuals. After bed rest, CD68 expression was increased in LBW (P=0.03) but not in NBW individuals. Furthermore, expression levels of all OXPHOS genes were reduced after bed rest in LBW (P ≤ 0.05) but not in NBW subjects and were negatively correlated with CD68 expression in LBW subjects (P ≤ 0.03 for all correlations). MCP1 expression and NF-κB activity were unaffected by bed rest, and IL6 expression was too low for accurate measurements. None of the inflammatory markers correlated with insulin sensitivity.
CONCLUSIONS
Although LBW subjects exhibit disproportionately elevated CD68 mRNA expression suggesting macrophage infiltration and reduced OXPHOS gene expression when exposed to bed rest, our data altogether do not support the notion that bed rest-induced (9 days) insulin resistance is caused by increased muscle inflammation.
Steen Larsen, Joachim Nielsen, Christina Neigaard Hansen, Lars Bo Nielsen, Flemming Wibrand, Nis Stride, Henrik Daa Schroder, Robert Boushel, Jørn Wulff Helge, Flemming Dela,et al.
Wiley
• Several biochemical measures of mitochondrial components are used as biomarkers of mitochondrial content and muscle oxidative capacity. However, no studies have validated these surrogates against a morphological measure of mitochondrial content in human subjects. • The most commonly used markers (citrate synthase activity, cardiolipin content, mitochondrial DNA content (mtDNA), complex I–V protein, and complex I–IV activity) were correlated with a measure of mitochondrial content (transmission electron microscopy) and muscle oxidative capacity (respiration in permeabilized fibres). • Cardiolipin content followed by citrate synthase activity and complex I activity were the biomarkers showing the strongest association with mitochondrial content. • mtDNA was found to be a poor biomarker of mitochondrial content. • Complex IV activity was closely associated with mitochondrial oxidative phosphorylation capacity.
S. Larsen, R. Rabøl, C. N. Hansen, S. Madsbad, J. W. Helge, and F. Dela
Springer Science and Business Media LLC
S. Larsen, N. Stride, M. Hey-Mogensen, C. N. Hansen, J. L. Andersen, S. Madsbad, D. Worm, J. W. Helge, and F. Dela
Springer Science and Business Media LLC
Mette Skovbro, Robert Boushel, Christina Neigaard Hansen, Jørn Wulff Helge, and Flemming Dela
American Physiological Society
Twenty one healthy untrained male subjects were randomized to follow a high-fat diet (HFD; 55–60E% fat, 25–30E% carbohydrate, and 15E% protein) or a normal diet (ND; 25–35E% fat, 55–60E% carbohydrate, and 10–15E% protein) for 21/2 wk. Diets were isocaloric and tailored individually to match energy expenditure. At 21/2 wk of diet, one 60-min bout of bicycle exercise (70% of maximal oxygen uptake) was performed. Muscle biopsies were obtained before and after the diet, immediately after exercise, and after 3-h recovery. Insulin sensitivity (hyperinsulinemic-euglycemic clamp) and intramyocellular triacylglycerol content did not change with the intervention in either group. Indexes of mitochondrial density were similar across the groups and intervention. Mitochondrial respiratory rates, measured in permeabilized muscle fibers, showed a 31 ± 11 and 26 ± 9% exercise-induced increase ( P < 0.05) in state 3 (glycolytic substrates) and uncoupled respiration, respectively. However, in HFD this increase was abolished. At recovery, no change from resting respiration was seen in either group. With a lipid substrate (octanoyl-carnitine with or without ADP), similar exercise-induced increases (31–62%) were seen in HFD and ND, but only in HFD was an elevated ( P < 0.05) respiratory rate seen at recovery. With HFD complex I and IV protein expression decreased ( P < 0.05 and P = 0.06, respectively). A fat-rich diet induces marked changes in the mitochondrial electron transport system protein content and in exercise-induced mitochondrial substrate oxidation rates, with the effects being present hours after the exercise. The effect of HFD is present even without effects on insulin sensitivity and intramyocellular lipid accumulation. An isocaloric high-fat diet does not cause insulin resistance.
Regitze Kraunsøe, Robert Boushel, Christina Neigaard Hansen, Peter Schjerling, Klaus Qvortrup, Mikael Støckel, Kári J. Mikines, and Flemming Dela
Wiley
Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra‐abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37°C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP (D) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOSD) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 ± 0.05 and 1.15 ± 0.06 pmol O2 s−1 mg−1, respectively) compared with subcutaneous (0.76 ± 0.04 and 0.98 ± 0.05 pmol O2 s−1 mg−1, respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.
Christina Neigaard Hansen, Lone Nielsen, and Bodil Norrild
Elsevier BV
R. Rabøl, R. Boushel, T. Almdal, C. N. Hansen, T. Ploug, S. B. Haugaard, C. Prats, S. Madsbad, and F. Dela
Wiley
Aim: Skeletal muscle insulin resistance has been linked to mitochondrial dysfunction. We examined how improvements in muscular insulin sensitivity following rosiglitazone (ROSI) or pioglitazone (PIO) treatment would affect muscle mitochondrial function in patients with type 2 diabetes mellitus (T2DM).
CHRISTINA NEIGAARD HANSEN, ZOHREH KETABI, MAIKEN WORSØE ROSENSTIERNE, CONNIE PALLE, HANS CHRISTIAN BOESEN, and BODIL NORRILD
Wiley
Persistent infection with high‐risk human papillomavirus (HPV) and expression of the proteins E6 and E7 is a prerequisite for development of cervical cancer. The distal non‐coding part of E6/E7 messengers from several HPV types is able to downregulate synthesis of a reporter gene through mechanisms with involvement of cytoplasmic polyadenylation elements (CPEs) in the messengers. We here show that the mRNA levels of one of the four known CPE‐binding proteins (CPEBs), the CPEB3, were downregulated in HPV‐positive cervical cancers, whereas in ovarian cancer the CPEB1 mRNA level was downregulated. In addition, we showed that the RNA levels of the widely used reference marker GAPDH were upregulated in both cancer forms, and the level of the reference marker U6snRNA was upregulated in cervical cancers. Moreover, a possible correlation between the degree of U6snRNA upregulation and cervical cancer propagation was shown. These changes observed in CPEB1 and CPEB3 might indicate regulatory functions of CPEBs in cancer development of HPV‐positive and HPV‐negative tumors, respectively, and the U6snRNA, GAPDH mRNA and CPEB1 mRNA levels may be useful as tumor markers for genital cancers although further investigations are needed.