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Ström, Kristoffer
Publications (8 of 8) Show all publications
Ström, K., Morales-Alamo, D., Ottosson, F., Edlund, A., Hjort, L., Jörgensen, S. W., . . . Hansson, O. (2018). N1-methylnicotinamide is a signalling molecule produced in skeletal muscle coordinating energy metabolism. Scientific Reports, 8(1), Article ID 3016.
Open this publication in new window or tab >>N1-methylnicotinamide is a signalling molecule produced in skeletal muscle coordinating energy metabolism
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 3016Article in journal (Refereed) Published
Abstract [en]

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. 

National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:miun:diva-33265 (URN)10.1038/s41598-018-21099-1 (DOI)000424985800054 ()29445118 (PubMedID)2-s2.0-85042133592 (Scopus ID)
Available from: 2018-03-14 Created: 2018-03-14 Last updated: 2018-03-19Bibliographically approved
McGawley, K., Juudas, E., Kazior, Z., Ström, K., Blomstrand, E., Hansson, O. & Holmberg, H.-C. (2017). No additional benefits of block-over evenly-distributed high-intensity interval training within a polarized microcycle. Frontiers in Physiology, 8(JUN), 1-12, Article ID 413.
Open this publication in new window or tab >>No additional benefits of block-over evenly-distributed high-intensity interval training within a polarized microcycle
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2017 (English)In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 8, no JUN, p. 1-12, article id 413Article in journal (Refereed) Published
Abstract [en]

Introduction: The current study aimed to investigate the responses to block- versus evenly-distributed high-intensity interval training (HIT) within a polarized microcycle. Methods: Twenty well-trained junior cross-country skiers (10 males, age 17.6 ± 1.5 and 10 females, age 17.3 ± 1.5) completed two, 3-week periods of training (EVEN and BLOCK) in a randomized, crossover-design study. In EVEN, 3 HIT sessions (5 × 4-min of diagonal-stride roller-skiing) were completed at a maximal sustainable intensity each week while low-intensity training (LIT) was distributed evenly around the HIT. In BLOCK, the same 9 HIT sessions were completed in the second week while only LIT was completed in the first and third weeks. Heart rate (HR), session ratings of perceived exertion (sRPE), and perceived recovery (pREC) were recorded for all HIT and LIT sessions, while distance covered was recorded for each HIT interval. The recovery-stress questionnaire for athletes (RESTQ-Sport) was completed weekly. Before and after EVEN and BLOCK, resting saliva and muscle samples were collected and an incremental test and 600-m time-trial (TT) were completed. Results: Pre- to post-testing revealed no significant differences between EVEN and BLOCK for changes in resting salivary cortisol, testosterone, or IgA, or for changes in muscle capillary density, fiber area, fiber composition, enzyme activity (CS, HAD, and PFK) or the protein content of VEGF or PGC-1α. Neither were any differences observed in the changes in skiing economy, VO2max or 600-m time-trial performance between interventions. These findings were coupled with no significant differences between EVEN and BLOCK for distance covered during HIT, summated HR zone scores, total sRPE training load, overall pREC or overall recovery-stress state. However, 600-m TT performance improved from pre- to post-training, irrespective of intervention (P = 0.003), and a number of hormonal and muscle biopsy markers were also significantly altered post-training (P < 0.05). Discussion: The current study shows that well-trained junior cross-country skiers are able to complete 9 HIT sessions within 1 week without compromising total work done and without experiencing greater stress or reduced recovery over a 3-week polarized microcycle. However, the findings do not support block-distributed HIT as a superior method to a more even distribution of HIT in terms of enhancing physiological or performance adaptions.

Keywords
cross-country skiing, endurance, junior athletes, muscle, periodization, recovery, stress, training load
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:miun:diva-30895 (URN)10.3389/fphys.2017.00413 (DOI)000403515100001 ()28659826 (PubMedID)2-s2.0-85020780112 (Scopus ID)
Available from: 2017-06-17 Created: 2017-06-17 Last updated: 2017-11-29Bibliographically approved
Su, J., Ekman, C., Oskolkov, N., Lahti, L., Ström, K., Brazma, A., . . . Hansson, O. (2015). A novel atlas of gene expression in human skeletal muscle reveals molecular changes associated with aging. Skeletal Muscle, 5, Article ID 35.
Open this publication in new window or tab >>A novel atlas of gene expression in human skeletal muscle reveals molecular changes associated with aging
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2015 (English)In: Skeletal Muscle, ISSN 2044-5040, Vol. 5, article id 35Article in journal (Refereed) Published
Abstract [en]

Background: Although high-throughput studies of gene expression have generated large amounts of data, most of which is freely available in public archives, the use of this valuable resource is limited by computational complications and non-homogenous annotation. To address these issues, we have performed a complete re-annotation of public microarray data from human skeletal muscle biopsies and constructed a muscle expression compendium consisting of nearly 3000 samples. The created muscle compendium is a publicly available resource including all curated annotation. Using this data set, we aimed to elucidate the molecular mechanism of muscle aging and to describe how physical exercise may alleviate negative physiological effects. Results: We find 957 genes to be significantly associated with aging (p < 0.05, FDR = 5 %, n = 361). Aging was associated with perturbation of many central metabolic pathways like mitochondrial function including reduced expression of genes in the ATP synthase, NADH dehydrogenase, cytochrome C reductase and oxidase complexes, as well as in glucose and pyruvate processing. Among the genes with the strongest association with aging were H3 histone, family 3B (H3F3B, p = 3.4 x 10(-13)), AHNAK nucleoprotein, desmoyokin (AHNAK, p = 6.9 x 10(-12)), and histone deacetylase 4 (HDAC4, p = 4.0 x 10(-9)). We also discover genes previously not linked to muscle aging and metabolism, such as fasciculation and elongation protein zeta 2 (FEZ2, p = 2.8 x 10(-8)). Out of the 957 genes associated with aging, 21 (p < 0.001, false discovery rate = 5 %, n = 116) were also associated with maximal oxygen consumption (VO2MAX). Strikingly, 20 out of those 21 genes are regulated in opposite direction when comparing increasing age with increasing VO2MAX. Conclusions: These results support that mitochondrial dysfunction is a major age-related factor and also highlight the beneficial effects of maintaining a high physical capacity for prevention of age-related sarcopenia.

Keywords
Skeletal muscle, Expression, Microarray, Aging, Mitochondrial dysfunction, Exercise
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:miun:diva-26572 (URN)10.1186/s13395-015-0059-1 (DOI)000362548600002 ()26457177 (PubMedID)2-s2.0-84943536506 (Scopus ID)
Available from: 2015-12-17 Created: 2015-12-17 Last updated: 2017-12-01Bibliographically approved
Oskolov, N., Ström, K., Holmberg, H.-C. & Hansson, O. (2015). GWAS OF HISTOLOGICAL PHENOTYPES PROVIDES INSIGHTS INTO THE GENETIC ARCHITECTURE OF HUMAN SKELETAL MUSCLE. In: ABSTRACT BOOK for the SGGD 2015: . Paper presented at SGGD 2015, Krakow.
Open this publication in new window or tab >>GWAS OF HISTOLOGICAL PHENOTYPES PROVIDES INSIGHTS INTO THE GENETIC ARCHITECTURE OF HUMAN SKELETAL MUSCLE
2015 (English)In: ABSTRACT BOOK for the SGGD 2015, 2015Conference paper, Oral presentation with published abstract (Refereed)
Abstract [en]

Introduction

Athlete performance depends to some extent on skeletal muscle fiber-type composition, i.e. athletes practicing endurance sports usually have a higher proportion of slow-twitch type I fibers, while fast-twitch type II fibers are more common for athletes in explosive sports. Insulin sensitivity has also been correlated with proportion of type I fibers, i.e. insulin resistant individuals having reduced muscle oxidative capacity with less oxidative type I and more glycolytic type IIx fibers.

Aims

Here we aimed to identify genetic variation and corresponding biological mechanisms affecting human skeletal muscle histology.

Methods

We performed a genome-wide association meta-analysis in Swedish males from 3 independent cohorts (n=656) with skeletal muscle histological phenotypes, e.g. capillary density, fibre-type distribution and area (measured by ATPas staining). Skeletal muscle microarray expression data (n=77) were used for an eQTL analysis of associated markers. Follow-up of capillary density was done in Swedish elite cross-country skiers (n=15).

Results

We identified 11 genome-wide significant (p<5x10-8) independent loci (STEAP, NYAP2, ADRA1B, TNFSF11, FAM155A, SLC22A10, FASLG, RBFOX1, FOXJ2, KCNMA1, RAB3GAP2) associated with 6 skeletal muscle phenotypes. eQTL-genes corresponding to the top associated variants were enriched in metabolic pathways. Using a population differentiation neutrality test we show that some of the fibre-type nominally associated loci (p<1x10-6) fall within regions of positive selection (i.e. FHIT, CRISP and ANXA1). The G-allele of rs115660502 (MAF=0.048) was significantly associated (p=2x10-8) with increased capillary density and also decreased expression of the nearby gene RAB3GAP2 (FDR=0.007). The G-allele also had a significantly higher frequency (MAF=0.122, p=0.029) in the cohort of Swedish elite skiers.

Conclusion

Our results add to our understanding of skeletal muscle architecture and indicate that there is a genetic component to it and that this might contribute to increased endurance performance in sport athletes.

National Category
Physiology Biological Sciences
Identifiers
urn:nbn:se:miun:diva-26815 (URN)
Conference
SGGD 2015, Krakow
Available from: 2016-01-04 Created: 2016-01-04 Last updated: 2018-01-10Bibliographically approved
Ekman, C., Elgzyri, T., Ström, K., Almgren, P., Parikh, H., Nitert, M. D., . . . Hansson, O. (2015). Less pronounced response to exercise in healthy relatives to type 2 diabetic subjects compared with controls. Journal of applied physiology, 119(9), 953-960
Open this publication in new window or tab >>Less pronounced response to exercise in healthy relatives to type 2 diabetic subjects compared with controls
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2015 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 119, no 9, p. 953-960Article in journal (Refereed) Published
Abstract [en]

Healthy first-degree relatives with heredity of type 2 diabetes (FH+) are known to have metabolic inflexibility compared with subjects without heredity for diabetes (FH-). In this study, we aimed to test the hypothesis that FH+ individuals have an impaired response to exercise compared with FH-. Sixteen FH+ and 19 FH- insulin-sensitive men similar in age, peak oxygen consumption ((V) over dot(O2 peak)), and body mass index completed an exercise intervention with heart rate monitored during exercise for 7 mo. Before and after the exercise intervention, the participants underwent a physical examination and tests for glucose tolerance and exercise capacity, and muscle biopsies were taken for expression analysis. The participants attended, on average, 39 training sessions during the intervention and spent 18.8 MJ on exercise. (V) over dot(O2 peak)/kg increased by 14%, and the participants lost 1.2 kg of weight and 3 cm waist circumference. Given that the FH- group expended 61% more energy during the intervention, we used regression analysis to analyze the response in the FH+ and FH- groups separately. Exercise volume had a significant effect on (V) over dot(O2 peak), weight, and waist circumference in the FH- group, but not in the FH+ group. After exercise, expression of genes involved in metabolism, oxidative phosphorylation, and cellular respiration increased more in the FH- compared with the FH+ group. This suggests that healthy, insulin-sensitive FH+ and FH- participants with similar age, (V) over dot(O2 peak), and body mass index may respond differently to an exercise intervention. The FH+ background might limit muscle adaptation to exercise, which may contribute to the increased susceptibility to type 2 diabetes in FH+ individuals.

Keywords
type 2 diabetes, exercise intervention, expression analysis, genetic predisposition, muscle
National Category
Health Sciences Sport and Fitness Sciences
Identifiers
urn:nbn:se:miun:diva-26513 (URN)10.1152/japplphysiol.01067.2014 (DOI)000364478200001 ()26338460 (PubMedID)2-s2.0-84946104150 (Scopus ID)
Available from: 2015-12-16 Created: 2015-12-16 Last updated: 2017-12-01Bibliographically approved
Keildson, S., Fadista, J., Ladenvall, C., Hedman, A. K., Elgzyri, T., Small, K. S., . . . Hansson, O. (2014). Expression of phosphofructokinase in skeletal muscle is influenced by genetic variation and associated with insulin sensitivity. Diabetes, 63(3), 1154-1165
Open this publication in new window or tab >>Expression of phosphofructokinase in skeletal muscle is influenced by genetic variation and associated with insulin sensitivity
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2014 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 3, p. 1154-1165Article in journal (Refereed) Published
Abstract [en]

Using an integrative approach in which genetic variation, gene expression, and clinical phenotypes are assessed in relevant tissues may help functionally characterize the contribution of genetics to disease susceptibility. We sought to identify genetic variation influencing skeletal muscle gene expression (expression quantitative trait loci [eQTLs]) as well as expression associated with measures of insulin sensitivity. We investigated associations of 3,799,401 genetic variants in expression of >7,000 genes from three cohorts (n = 104). We identified 287 genes with cis-acting eQTLs (false discovery rate [FDR] <5%; P < 1.96×1025) and 49 expression-insulin sensitivity phenotype associations (i.e., fasting insulin, homeostasis model assessment-insulin resistance, and BMI) (FDR <5%; P = 1.34×1024). One of these associations, fasting insulin/phosphofructokinase (PFKM), overlaps with an eQTL. Furthermore, the expression of PFKM, a rate-limiting enzyme in glycolysis, was nominally associated with glucose uptake in skeletal muscle (P = 0.026; n = 42) and overexpressed (Bonferroni-corrected P = 0.03) in skeletal muscle of patients with T2D (n = 102) compared with normoglycemic controls (n = 87). The PFKM eQTL (rs4547172; P = 7.69 × 1026) was nominally associated with glucose uptake, glucose oxidation rate, intramuscular triglyceride content, and metabolic flexibility (P = 0.016-0.048; n = 178). We explored eQTL results using published data from genome-wide association studies (DIAGRAM and MAGIC), and a proxy for the PFKM eQTL (rs11168327; r 2 = 0.75) was nominally associated with T2D (DIAGRAM P = 2.7×1023). Taken together, our analysis highlights PFKM as a potential regulator of skeletal muscle insulin sensitivity. © 2014 by the American Diabetes Association..

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:miun:diva-22055 (URN)10.2337/db13-1301 (DOI)000331614200035 ()2-s2.0-84894499261 (Scopus ID)
Note

Language of Original Document: English

Available from: 2014-05-30 Created: 2014-05-30 Last updated: 2017-12-05Bibliographically approved
Planck, T., Shahida, B., Parikh, H., Ström, K., Asman, P., Brorson, H., . . . Lantz, M. (2014). Smoking Induces Overexpression of Immediate Early Genes in Active Graves' Ophthalmopathy. Thyroid, 24(10), 1524-1532
Open this publication in new window or tab >>Smoking Induces Overexpression of Immediate Early Genes in Active Graves' Ophthalmopathy
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2014 (English)In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 24, no 10, p. 1524-1532Article in journal (Refereed) Published
Abstract [en]

Background: Cigarette smoking is a risk factor for the development of Graves' ophthalmopathy (GO). In a previous study of gene expression in intraorbital fat, adipocyte-related immediate early genes (IEGs) were overexpressed in patients with GO compared to controls. We investigated whether IEGs are upregulated by smoking, and examined other pathways that may be affected by smoking. Methods: Gene expression in intraorbital fat was studied in smokers (n=8) and nonsmokers (n=8) with severe active GO, as well as in subcutaneous fat in thyroid-healthy smokers (n=5) and nonsmokers (n=5) using microarray and real-time polymerase chain reaction (PCR). Results: With microarray, eight IEGs were upregulated more than 1.5-fold in smokers compared to nonsmokers with GO. Five were chosen for confirmation and were also overexpressed with real-time PCR. Interleukin-1 beta/IL-1B/(2.3-fold) and interleukin-6/IL-6/(2.4-fold) were upregulated both with microarray and with real-time PCR in smokers with GO compared to nonsmokers. Major histocompatibility complex, class II, DR beta 1/HLA-DRB1/was upregulated with microarray (2.1-fold) and with borderline significance with real-time PCR. None of these genes were upregulated in smokers compared to nonsmokers in subcutaneous fat. Conclusions: IEGs, IL-1B, and IL-6 were overexpressed in smokers with severe active GO compared to nonsmokers, suggesting that smoking activates pathways associated with adipogenesis and inflammation. This study underlines the importance of IEGs in the pathogenesis of GO, and provides evidence for possible novel therapeutic interventions in GO. The mechanisms activated by smoking may be shared with other conditions such as rheumatoid arthritis.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:miun:diva-23439 (URN)10.1089/thy.2014.0153 (DOI)000342742800012 ()2-s2.0-84907438895 (Scopus ID)
Available from: 2015-01-09 Created: 2014-11-17 Last updated: 2017-12-05Bibliographically approved
Axling, U., Olsson, C., Xu, J., Fernandez, C., Larsson, S., Ström, K., . . . Berger, K. (2012). Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL/6J mice. Nutrition and Metabolism, 9, Article ID 105.
Open this publication in new window or tab >>Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL/6J mice
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2012 (English)In: Nutrition and Metabolism, ISSN 1743-7075, Vol. 9, article id 105Article in journal (Refereed) Published
Abstract [en]

Background: Type 2 diabetes is associated with obesity, ectopic lipid accumulation and low-grade inflammation. A dysfunctional gut microbiota has been suggested to participate in the pathogenesis of the disease. Green tea is rich in polyphenols and has previously been shown to exert beneficial metabolic effects. Lactobacillus plantarum has the ability to metabolize phenolic acids. The health promoting effect of whole green tea powder as a prebiotic compound has not been thoroughly investigated previously. Methods. C57BL/6J mice were fed a high-fat diet with or without a supplement of 4% green tea powder (GT), and offered drinking water supplemented with Lactobacillus plantarum DSM 15313 (Lp) or the combination of both (Lp + GT) for 22 weeks. Parameters related to obesity, glucose tolerance, lipid metabolism, hepatic steatosis and inflammation were examined. Small intestinal tissue and caecal content were collected for bacterial analysis. Results: Mice in the Lp + GT group had significantly more Lactobacillus and higher diversity of bacteria in the intestine compared to both mice in the control and the GT group. Green tea strongly reduced the body fat content and hepatic triacylglycerol and cholesterol accumulation. The reduction was negatively correlated to the amount of Akkermansia and/or the total amount of bacteria in the small intestine. Markers of inflammation were reduced in the Lp + GT group compared to control. PLS analysis of correlations between the microbiota and the metabolic variables of the individual mice showed that relatively few components of the microbiota had high impact on the correlation model. Conclusions: Green tea powder in combination with a single strain of Lactobacillus plantarum was able to promote growth of Lactobacillus in the intestine and to attenuate high fat diet-induced inflammation. In addition, a component of the microbiota, Akkermansia, correlated negatively with several metabolic parameters known to be risk factors for the development of type 2 diabetes.

Keywords
Akkermansia; C57BL/6J; Green tea; Inflammation; Lactobacillus plantarum; Microbiota; Obesity; Type 2 diabetes
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:miun:diva-28875 (URN)10.1186/1743-7075-9-105 (DOI)2-s2.0-84869866467 (Scopus ID)
Available from: 2016-09-22 Created: 2016-09-22 Last updated: 2017-05-18Bibliographically approved
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