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- Sarwar, Nadeem, et al.
(author)
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Interleukin-6 receptor pathways in coronary heart disease : a collaborative meta-analysis of 82 studies
- 2012
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In: The Lancet. - New York, NY, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9822, s. 1205-1213
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Journal article (peer-reviewed)abstract
- Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
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- Wessel, Jennifer, et al.
(author)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Journal article (peer-reviewed)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 4. |
- Bellman, Jakob, et al.
(author)
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Loading enhances glucose uptake in muscles, bones, and bone marrow of lower extremities in humans.
- 2024
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In: The Journal of clinical endocrinology and metabolism. - 1945-7197.
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Journal article (peer-reviewed)abstract
- Increased standing time has been associated with improved health, but the underlying mechanism is unclear.We herein investigate if increased weight loading increases energy demand and thereby glucose uptake (GU) locally in bone and/or muscle in the lower extremities.In this single-center clinical trial with randomized crossover design (ClinicalTrials.gov ID, NCT05443620), we enrolled 10 men with body mass index (BMI) between 30 and 35kg/m2. Participants were treated with both high load (standing with weight vest weighing 11% of body weight) and no load (sitting) on the lower extremities. GU was measured using whole-body quantitative positron emission tomography/computed tomography (PET/CT) imaging. The primary endpoint was the change in GU ratio between loaded bones (i.e. femur and tibia) and non-loaded bones (i.e. humerus).High load increased the GU ratio between lower and upper extremities in cortical diaphyseal bone (e.g. femur/humerus ratio increased by 19%, p=0.029), muscles (e.g. m. quadriceps femoris/m. triceps brachii ratio increased by 28%, p=0.014) and in certain bone marrow regions (femur/humerus diaphyseal bone marrow region ratio increased by 17%, p=0.041). Unexpectedly, we observed the highest GU in the bone marrow region of vertebral bodies, but its GU was not affected by high load.Increased weight-bearing loading enhances GU in muscles, cortical bone, and bone marrow of the exposed lower extremities. This could be interpreted as increased local energy demand in bone and muscle caused by increased loading. The physiological importance of the increased local GU by static loading remains to be determined.
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| 5. |
- Heid, Iris M, et al.
(author)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Journal article (peer-reviewed)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 6. |
- Hägg, Daniel, 1974, et al.
(author)
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Osteoblast-lineage cells regulate metabolism and fat mass
- 2023
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In: Current Opinion in Endocrine and Metabolic Research. - 2451-9650. ; 31
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Research review (peer-reviewed)abstract
- As energy depots in many circumstances have been limited during evolution, it is necessary to prioritize how to manage energy resources. In this review we summarize data from the last 15 years indicating that osteoblast-lineage cells are regulators of whole-body energy metabolism and fat mass. We focus mainly on three factors, osteocalcin, lipocalin-2 and sclerostin, that are released by osteoblast-lineage cells and proposed to exert endocrine effects on metabolism. In addition, we present a hypothesis on why osteoblast-lineage cells during evolution have developed a function to regulate metabolism and fat mass. We propose that osteoblast-lineage cells through the osteocyte network in bone are sensors of gravitational forces induced by body mass and gravity on land-living species. By sensing the body weight, the osteoblastlineage cells may then feed-back this information on the whole-body nutritional status via osteoblast-derived endocrine factors or via the nervous system to regulate energy metabolism and fat mass.
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| 7. |
- Jansson, Alexander, et al.
(author)
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Träningsråd till dig som ska genomföra tester av fysisk förmåga på Plikt- och prövningsverket
- 2023
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Reports (other academic/artistic)abstract
- På Plikt- och prövningsverket genomförs flera olika tester. När det kommer till att testa de prövandes fysiska förmåga används bland annat ett konditionstest på cykel och ett isokinetiskt styrketest som kallas Isokai. I den här texten ges information om testerna, grundläggande träningsråd för att klara dessa samt råd inför fortsatt träning. Råden är uppdelade i två delar. I den första delen beskrivs träningsråd för styrketräning och i den andra för konditionsträning.
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| 8. |
- Jansson, Daniel T., et al.
(author)
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Metabolism, inflammation and postoperative time are the key to early diagnosis of anastomotic leak
- 2019
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In: Journal of Surgery and Surgical Research. - : Peertechz Publications Private Limited. - 2455-2968. ; 5:2
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Journal article (peer-reviewed)abstract
- Objective: The aim of the study was to find laboratory samples for early diagnosis of anastomotic leak.Summary background data: Anastomotic leakage after rectal cancer surgery is a severe complication with high mortality. Outcome is highly dependent on early diagnosis.Methods: 29 patients were investigated postoperatively after having undergone low anterior resection due to cancer recti. Patient outcomes were divided into three groups: Anastomotic leak in 7 patients, other complications in 9 patients and 13 patients who were free of complications. Patients were monitored every 6th hour with blood and intraperitoneal samples in order to identify laboratory markers for early detection of anastomotic leakage. An anastomotic leak index was created, a scoring system where points count for values higher than reference values of CRP and interleukin 6 in blood and intraperitoneal lactate, lactate/pyruvate ratio and interleukin 6 were measured at 18, 24, 42 and 48 hours postoperatively.Results: Significant differences between groups were found regarding CRP, Interleukin 6, fibrinogen and D-dimer in blood. Intraperitoneal differences were found not only in lactate and lactate/pyruvate ratio measured by microdialysis, significant differences in interleukin 6, interleukin 10 and tumour necrosis factor-α could also be demonstrated between the groups. The anastomotic leak index had a sensitivity and specificity of 86% (p=0.0007).Conclusions: The most important factor was time after operation. No laboratory parameter in itself could predict an anastomotic leak but the anastomotic leak index was a useful tool in the monitoring and assessment of clinical outcome.Mini abstract: Patients with anastomotic leak after rectal surgery were monitored with higher intraperitoneal cytokines and lactate/pyruvate ratio. The results suggest intraperitoneal microdialysis combined with blood samples of CRP and IL 6 as a feasible method for early diagnosis of anastomotic leak.
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| 9. |
- Jansson, John-Olov, 1954, et al.
(author)
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Body weight homeostat that regulates fat mass independently of leptin in rats and mice.
- 2018
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 115:2, s. 427-432
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Journal article (peer-reviewed)abstract
- Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.
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| 10. |
- Jansson, John-Olov, 1954, et al.
(author)
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The dual hypothesis of homeostatic body weight regulation, including gravity-dependent and leptin-dependent actions.
- 2023
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In: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. - 1471-2970. ; 378:1888
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Research review (peer-reviewed)abstract
- Body weight is tightly regulated when outside the normal range. It has been proposed that there are individual-specific lower and upper intervention points for when the homeostatic regulation of body weight is initiated. The nature of the homeostatic mechanisms regulating body weight at the lower and upper ends of the body weight spectrum might differ. Previous studies demonstrate that leptin is the main regulator of body weight at the lower end of the body weight spectrum. We have proposed that land-living animals use gravity to regulate their body weight. We named this homeostatic system the gravitostat and proposed that there are two components of the gravitostat. First, an obvious mechanism involves increased energy consumption in relation to body weight when working against gravity on land. In addition, we propose that there exists a component, involving sensing of the body weight by osteocytes in the weight-bearing bones, resulting in a feedback regulation of energy metabolism and body weight. The gravity-dependent homeostatic regulation is mainly active in obese mice. We, herein, propose the dual hypothesis of body weight regulation, including gravity-dependent actions (= gravitostat) at the upper end and leptin-dependent actions at the lower end of the body weight spectrum. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.
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