| 1. |
- Bauzá-Thorbrügge, Marco, et al.
(författare)
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Adipocyte-specific ablation of the Ca2+ pump SERCA2 impairs whole-body metabolic function and reveals the diverse metabolic flexibility of white and brown adipose tissue.
- 2022
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Ingår i: Molecular metabolism. - : Elsevier BV. - 2212-8778. ; 63
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Tidskriftsartikel (refereegranskat)abstract
- Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) transports Ca2+ from the cytosol into the endoplasmic retitculum (ER) and is essential for appropriate regulation of intracellular Ca2+ homeostasis. The objective of this study was to test the hypothesis that SERCA pumps are involved in the regulation of white adipocyte hormone secretion and other aspects of adipose tissue function and that this control is disturbed in obesity-induced type-2 diabetes.SERCA expression was measured in isolated human and mouse adipocytes as well as in whole mouse adipose tissue by Western blot and RT-qPCR. To test the significance of SERCA2 in adipocyte functionality and whole-body metabolism, we generated adipocyte-specific SERCA2 knockout mice. The mice were metabolically phenotyped by glucose tolerance and tracer studies, histological analyses, measurements of glucose-stimulated insulin release in isolated islets, and gene/protein expression analyses. We also tested the effect of pharmacological SERCA inhibition and genetic SERCA2 ablation in cultured adipocytes. Intracellular and mitochondrial Ca2+ levels were recorded with dual-wavelength ratio imaging and mitochondrial function was assessed by Seahorse technology.We demonstrate that SERCA2 is downregulated in white adipocytes from patients with obesity and type-2 diabetes as well as in adipocytes from diet-induced obese mice. SERCA2-ablated adipocytes display disturbed Ca2+ homeostasis associated with upregulated ER stress markers and impaired hormone release. These adipocyte alterations are linked to mild lipodystrophy, reduced adiponectin levels, and impaired glucose tolerance. Interestingly, adipocyte-specific SERCA2 ablation leads to increased glucose uptake in white adipose tissue while the glucose uptake is reduced in brown adipose tissue. This dichotomous effect on glucose uptake is due to differently regulated mitochondrial function. In white adipocytes, SERCA2 deficiency triggers an adaptive increase in fibroblast growth factor 21 (FGF21), increased mitochondrial uncoupling protein 1 (UCP1) levels, and increased oxygen consumption rate (OCR). In contrast, brown SERCA2 null adipocytes display reduced OCR despite increased mitochondrial content and UCP1 levels compared to wild type controls.Our data suggest causal links between reduced white adipocyte SERCA2 levels, deranged adipocyte Ca2+ homeostasis, adipose tissue dysfunction and type-2 diabetes.
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| 2. |
- Bernhardsson, Christian, et al.
(författare)
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Environmental radiation baseline around the Belarusian nuclear power plant – assessments in Belarus and Lithuania
- 2023
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Ingår i: Medical Physics in the Baltic States : Proceedings of the 16<sup>th</sup> International Conference on Medical Physics - Proceedings of the 16<sup>th</sup> International Conference on Medical Physics. - 1822-5721. ; , s. 121-125
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Konferensbidrag (refereegranskat)abstract
- Prior to the operation of the first Belarussian nuclear power plant (BelNPP), the baseline of the radiation environment was determined within a radius of about 30 km from BelNPP. This independent assessment was carried out during two expeditions in 2019. In 2022, a similar survey was carried out (during the initialoperation of BelNPP) on the Lithuanian side of the boarder. Here we present the overall project and some general results of the baseline assessments.
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| 3. |
- Eriksson Stenström, Kristina, et al.
(författare)
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Identifying radiologically important ESS-specific radionuclides and relevant detection methods
- 2020
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Bok (refereegranskat)abstract
- The European Spallation Source (ESS) is under construction in the outskirts of Lund in southern Sweden. When ESS has entered the operational phase in a few years, an intense beam of high-energy protons will not only produce the desired spallation neutrons from a large target of tungsten, but a substantial number of different radioactive by-products will also be generated. A small part of these will be released to the environment during normal operation. During an accident scenario, a wide range of gases and aerosols may be released from the tungsten target. The palette of radionuclides generated in the ESS target will differ from that of e.g. medical cyclotrons or nuclear power plants, thus presenting new challenges e.g. in the required environmental monitoring to ensure that dose limits to the public are not exceeded. This project (SSM2018-1636), financed by the Swedish Radiation Safety Authority (SSM), aimed to strengthen competence at Lund University for measurement and analysis of ESS-specific radionuclides. First, an extensive literature review, including modelling as well as experimental analyses, of ESS-relevant radionuclides was performed. We found that radionuclide production in particle accelerators is well-known, while experience with tungsten targets is very limited. As a second part of the project, an independent simplified model of the ESS target sector for the calculations of radionuclide production in the ESS tungsten target was developed using the FLUKA code. We conclude that we have a fairly good agreement with results of other authors, except for 148Gd, and that the calculated radionuclide composition is sensitive to the nuclear interaction models used.In the third part of the project, known environmental measurement technologies for various ESS-relevant radionuclides were reviewed, focussing on pure difficult-to-measure alpha- and beta-emitters. Liquid scintillation counting (LSC) is a suitable technique e.g. for the important beta emitters 3H, 14C, 35S, 31P and 33P. Several ESS radionuclides of relevance for dose estimates have never been investigated by environmental analytical techniques, due to their absence in the normal environment. Alpha spectrometry seems promising for the analysis of alpha-emitting lanthanides, in particular for 148Gd. Among the many types of mass spectrometry techniques, ICP-MS (inductively coupled plasma mass spectrometry) and AMS (accelerator mass spectrometry) seem to be the most suitable for the analysis of long-lived ESS radionuclides in environmental samples (e.g. 243Am and possibly lanthanides for ICP-MS and 10Be, 14C, 32Si, 36Cl, 60Fe and 129I for AMS).Three experimental parts were performed during the project, related to initiation of radioactivity measurements of aerosols at Lund University, mapping of environmental tritium in the Lund area, and establishment of a method to measure tritium in urine followed by a study of tritium in persons presently living or working in Lund. Aerosols were collected at a rural background station (Hyltemossa near Perstorp, northern Skåne) using a high-volume aerosol sampler with automatic filter change (DHA-80, Digitel). Gamma spectrometry measurements of 7Be agreed rather well with results from a nearby air monitoring station (SSM/FOI). Tritium (radioactive hydrogen) is expected to dominate the source term from the ESS target station to the environment. We have performed several investigations to monitor the current situation of tritium in Lund using LSC: the matrices investigated included air humidity, precipitation, pond water, indoor air at one accelerator facility and urine from the general public as well as from persons who may be occupationally exposed to tritium. Environmental tritium was generally very low (<3.4 Bq L-1), with somewhat higher concentration in the springtime than during the rest of the year. Tritium in the vast majority of the 55 urine samples was also very low: only a few exposed workers were found to have up to 11 Bq L-1 in their urine, which still is very low compared to e.g. reactor workers. Suggestions for further actions and work related to measurement and analysis of ESS relevant radionuclides are presented.
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| 4. |
- Eriksson Stenström, Kristina, et al.
(författare)
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PREOPERATIONAL ASSESSMENT OF 14C IN THE VINICINITY OF THE BELARUSIAN NUCLEAR POWER PLANT
- 2021
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Ingår i: Medical Physics in the Baltic States : Proceedings of the 15th International Conference - Proceedings of the 15th International Conference. - 1822-5721. ; , s. 133-137
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Konferensbidrag (refereegranskat)abstract
- As part of an independent assessment of the preoperational radiation environment around the Ostrovets nuclear power plant in Belarus, grass and foodstuffs were collected in 2019 for 14C analysis. The preoperational 14C specific activities in the Ostrovets region were shown to be similar to that of European data from other uncontaminated sites.
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| 5. |
- Gondo, Thamani Freedom, et al.
(författare)
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Extractability, selectivity, and comprehensiveness in supercritical fluid extraction of seaweed using ternary mixtures of carbon dioxide, ethanol, and water
- 2023
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Ingår i: Journal of chromatography. A. - 0021-9673. ; 1706, s. 464267-464267
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Tidskriftsartikel (refereegranskat)abstract
- It is well-known that an ideal extraction method enabling quantitative analysis should give complete extraction of the target analytes as well as minimal co-extraction of unwanted matrix substances. If the extraction method is part of a nontarget screening protocol, the desired analytes can differ widely in terms of chemical properties. In chromatography, terminologies such as recovery, selectivity, and comprehensiveness are well-established and can easily be determined. However, in extraction, these concepts are much less developed. Hence, the aim of our research is to develop and scrutinize theory in extraction with respect to numerical descriptors for extractability, selectivity, and comprehensiveness. Our approach is based on experiments determining the extractability of target analytes and selected interferences. As a case study, we use a pooled sample of three species of seaweed (Alaria esculenta, Laminaria digitata and Ascophyllum nodosum). Target analytes are β-carotene, fucoxanthin, δ-tocopherol, and phloroglucinol; and selected interferences are carbohydrates, proteins, ash, arsenic, and chlorophyll a. As a "green and clean" extraction technique, supercritical fluid extraction (SFE) using mixtures of CO 2, ethanol and water were explored using a design of experiment. The temperature was varied between 40-80°C, and the pressure was held constant at 300 bar. Obtained results clearly demonstrate that highest relative selectivity was achieved with CO 2 containing only 5 vol% of ethanol and no water, which primarily enabled high extractability of β-carotene, and yielding an extract free of carbohydrates, proteins, and toxic metals such as arsenic. Best methods for highest extractability of the other target analytes varied quite widely. Analytes requiring the highest water content (fucoxanthin and phloroglucinol), also resulted in the lowest relative selectivity. Maximum relative comprehensiveness was achieved using CO 2/ethanol/water (40/55/5, v/v/v) at 70°C and 300 bar. Our study demonstrates the feasibility of using relative quantitative descriptors for extractability, selectivity, and comprehensiveness, in optimization strategies for analytical extractions.
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| 6. |
- Hayes, Sandra Christine, et al.
(författare)
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The Effect of Exercise for the Prevention and Treatment of Cancer-Related Lymphedema : A Systematic Review with Meta-analysis
- 2022
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Ingår i: Medicine and Science in Sports and Exercise. - 0195-9131. ; 54:8, s. 1389-1399
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Forskningsöversikt (refereegranskat)abstract
- Introduction The purpose of this systematic review and meta-analysis was to evaluate the effects of exercise on (i) the prevention of cancer-related lymphedema (CRL) and (ii) the treatment of CRL, lymphedema-associated symptoms, and other health outcomes among individuals with CRL. Methods An electronic search was undertaken for exercise studies measuring lymphedema and involving individuals at risk of developing or with CRL. The Effective Public Health Practice Project Quality scale was used to assess study quality, and overall quality of evidence was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach. Meta-analyses were performed to evaluate effects of exercise on CRL incidence, existing CRL status, lymphedema-associated symptoms, and health outcomes. Results Twelve studies (n = 1955; 75% moderate-high quality) and 36 studies (n = 1741; 58% moderate-high quality) were included in the prevention and treatment aim, respectively. Relative risk of developing CRL for those in the exercise group compared with the nonexercise group was 0.90 (95% confidence interval (CI), 0.72 to 1.13) overall and 0.49 (95% CI, 0.28 to 0.85) for those with five or more lymph nodes removed. For those with CRL in the exercise group, the standardized mean difference (SMD) before to after exercise of CRL was-0.11 (95% CI,-0.22 to 0.01), and compared with usual care postintervention, the SMD was-0.10 (95% CI,-0.24 to 0.04). Improvements after intervention were observed for pain, upper-body function and strength, lower-body strength, fatigue, and quality of life for those in the exercise group (SMD, 0.3-0.8; P < 0.05). Conclusions Findings support the application of exercise guidelines for the wider cancer population to those with or at risk of CRL. This includes promotion of aerobic and resistance exercise, and not just resistance exercise alone, as well as unsupervised exercise guided by symptom response.
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| 7. |
- Häggström, Margaretha, 1962, et al.
(författare)
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Att undervisa i hållbar utveckling - Relationellt perspektiv
- 2022
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Hur kan lärare arbeta med hållbar utveckling i en tid då globala kriser och klimatförändringar väcker både rädsla och oro? Och hur kan elever samtidigt känna hopp inför sin framtid och sitt vuxna liv? Dessa frågor är utgångspunkt för det utvecklings- och forskningsprojekt som utgör basen i denna bok. Du får följa med i berättelser som lärare och elever skapat tillsammans för att utveckla kunskap om social, ekologisk och ekonomisk hållbarhet. Boken redogör för de pedagogiska utgångspunkterna, men ger också rikligt med praktiska exempel på metoder och former för undervisning i och genom demokratiska och relationella förhållningssätt. Du får konkreta tips på hur du kan integrera hållbar utveckling i undervisningen. Såväl kritiska aspekter som lärdomar och möjligheter lyfts fram. I centrum står eleven och läraren utifrån det relationspedagogiska perspektivet. Att undervisa i hållbar utveckling: Relationellt perspektiv vänder sig till lärarstudenter och verksamma lärare i årskurs F-6. Bokens syfte är att inspirera, stödja och utgöra diskussionsunderlag i skolans arbete med miljöperspektivet och hållbar utveckling.
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| 8. |
- Johansson, Karin, et al.
(författare)
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Compression Treatment of Breast Edema : A Randomized Controlled Pilot Study
- 2020
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Ingår i: Lymphatic Research and Biology. - : Mary Ann Liebert Inc. - 1539-6851 .- 1557-8585. ; 18:2, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients treated for breast cancer with breast conserving surgery and radiotherapy (RT) often complain about swelling, heaviness, and pain in the treated breast. This pilot study was undertaken to examine if compression therapy was effective as an early treatment to reduce breast edema and symptoms assessed by Visual Analogue Scale (VAS). Methods and Results: Fifty-six breast cancer-treated women with breast edema, diagnosed by the measurement of tissue water content by tissue dielectric constant (TDC) technique 3 months post-RT, were randomized to either an intervention group, wearing a sports bra of compression type, or a control group, wearing a standard bra daily for 9 months when tissue water content in breast, upper arm, and lateral thorax of the operated side, and symptoms assessed by VAS were evaluated. No differences were found between the groups at start or end of study concerning tissue water content or VAS. However, within both groups, a significant reduction in tissue water content and experience of heaviness was found. Conclusion: Breast edema as well as experience of heaviness in the affected breast found at 3 months post-RT decreased after 9 months independent of whether a sports bra of compression type or a standard bra was used.
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| 9. |
- Johnsson, Charlotta, et al.
(författare)
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Historical female influencers in automatic control
- 2023
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Ingår i: IFAC Proceedings Volumes (IFAC-PapersOnline). - 2405-8963. ; 56:2, s. 4693-4698
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Tidskriftsartikel (refereegranskat)abstract
- Over the last century, many women have contributed to the field of control engineering. Nevertheless, women are generally in the minority. This article highlights the contribution of women since the inception of control engineering to highlight good exemples to coming generations. A repository of portraits of women in control engineering is currently being curated and made available through the university of Lund website. The main purpose is to provide role models for future generations of control engineers. This article describes the need for role models as a means to change the situation and attract more women to control engineering in the future. Two portraits in the repository – those of Irmgard Flügge-Lotz and Nina Thornhill – are presented here. Ideas on how to use this resource are provided.
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| 10. |
- Jönsson, Charlotta, et al.
(författare)
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Circumferential Measurements to Calculate Lower Limb Volume in Persons with Lymphedema : What Segment Length Is to Be Recommended?
- 2023
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Ingår i: Lymphatic Research and Biology. - : Mary Ann Liebert Inc. - 1539-6851 .- 1557-8585. ; 21:3, s. 275-282
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circumferential measurements (CMs) every 4th cm are commonly used to assess lower limb volume (LLV), but fewer measurements would be less time-consuming. The aim of this study was therefore to establish the agreement between LLV measurements derived from CM every 4th cm (V4), 8th cm (V8), and 12th cm (V12), and to evaluate the intrarater test-retest reliability for each of the three measurement methods in persons with lower limb lymphedema (LLL). Methods and Results: Forty-two persons with unilateral or bilateral LLL were measured twice, 2 weeks apart. Volume measurements for the V4, V8, and V12 methods were derived using CM. The agreement was evaluated using intraclass correlation coefficient (ICC3.1) and Bland-Altman graphs including 95% limits of agreement (LOA). The reliability was evaluated using ICC2.1 and standard error of measurement (SEM%) and smallest real difference (SRD%). The agreement was high for the V4 and V8 methods (ICC 0.999), and for the V4 and V12 methods (ICC 0.998). The graphs revealed slightly higher agreement between the V4 and V8 than between the V4 and V12 methods visualized by the 95% LOA (-117 to 62 and -236 to 132 mL, respectively). For all three measurement methods, the test-retest reliability was high (ICC 0.993-0.995) and the measurement error low (SEM%: 1.2%-1.4% and SRD%: 3.4%-3.8%). Conclusions: The higher agreement between the V4 and V8 methods than between V4 and V12, and the high test-retest reliability in LLV measurements support the V8 method to replace the V4 method in persons with LLL.
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| 11. |
- Jönsson, Charlotta, et al.
(författare)
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Impedance of Extracellular Fluid, Volume, and Local Tissue Water Can Be Reliably Measured in People with Lower Limb Lymphedema
- 2022
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Ingår i: Physical Therapy. - : Oxford University Press (OUP). - 0031-9023 .- 1538-6724. ; 102:5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Lower limb lymphedema (LLL) is a chronic condition. To be able to evaluate changes of LLL over time and effects of interventions reliable measurement methods are important. Currently, there is limited knowledge of the reliability of commonly used measurement methods in LLL. The study objective was to evaluate the test-retest (intrarater) reliability of impedance of extracellular fluid, volume, and local tissue water measurements in people with unilateral or bilateral LLL and measurement errors both for a group of people and for a single individual.METHODS: Forty-two people with mild to moderate unilateral or bilateral, primary or secondary LLL were measured twice, 2 weeks apart. Impedance of extracellular fluid was measured by bioimpedance spectroscopy and calculated as arm-to-leg ratio, volume with circumference measurements every 4 cm, and local tissue water with tissue dielectric constant at 14 points. Test-retest reliability was evaluated using the ICC(2,1), changes in the mean, standard error of measurement in relative terms (SEM%), and the smallest real difference in relative terms (SRD%).RESULTS: For the impedance ratio, the reliability was high [ICC(2,1) = 0.79 to 0.90] and the measurement errors were acceptable (SEM% = 5.0%-5.2%; SRD% = 14.0%-14.4%). For volume, the reliability was high (ICC = 0.99) and the measurement errors were low (SEM% = 1.1%-1.7%; SRD% = 3.1%-4.6%). For the tissue dielectric constant, the reliability was fair to excellent [ICC(2,1) = 0.68 to 0.96] and the measurement errors were acceptable (SEM% = 4.2%-9.7%; SRD% = 11.7%-26.8%).CONCLUSIONS: Impedance of extracellular fluid, volume, and local tissue water are reliable in people with mild to moderate LLL. The measurement errors were acceptable in all 3 methods indicating that real, clinical changes in lymphedema can be measured both for a group of people and a single individual.
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| 12. |
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| 13. |
- Jönsson, Charlotta, et al.
(författare)
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Test-Retest Reliability of Volume and Local Tissue Water Measurements in Lower Limbs of Healthy Women and Men
- 2020
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Ingår i: Lymphatic Research and Biology. - : Mary Ann Liebert Inc. - 1539-6851 .- 1557-8585. ; 18:3, s. 261-269
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Tidskriftsartikel (refereegranskat)abstract
- Background: Measurements of lower limb (LL) volume and local tissue water by tissue dielectric constant (TDC) are common in lymphedema management. Knowledge of normal variability in health subjects is important and can serve as a base for early lymphedema diagnosis but is currently lacking. The aim of this study was to evaluate test-retest reliability of LL volume and TDC values in healthy women and men. Methods and Results: Thirty-three women and 28 men were measured twice, 2 weeks apart. Volume was calculated from circumferential measurements every 4 cm and TDC in 14 points. Test-retest reliability was evaluated using intraclass correlation coefficient (ICC), changes in the mean, standard error of measurement in percentage (SEM%), and smallest real difference in percentage (SRD%). For volume, reliability was high (ICC 0.99) and measurement errors were low in both women and men (SEM%: 1.1%-1.3%; SRD%: 3.1%-3.6%). For TDC, reliability was fair to excellent in women (ICC 0.63-0.93) and poor to excellent in men (ICC 0.21-0.89). Measurement errors were acceptable in all points in women (SEM%: 3.9%-10.2%; SRD% 10.8%-28.2%), but only in 11 points in men (SEM%: 3.9%-14.5%; SRD%: 10.9%-40.1%). The points close to bone and tendons in men had lower reliability and higher measurement errors. Conclusion: Measurements of LL volume and TDC are reliable in healthy women and men; both methods can be recommended. However, TDC points close to bone and tendons in men should be used with caution.
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| 14. |
- Levay, Charlotta, et al.
(författare)
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Quantified control in healthcare work : Suggestions for future research
- 2020
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Ingår i: Financial Accountability & Management. - : Wiley. - 1468-0408 .- 0267-4424. ; 36:4, s. 461-478
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Tidskriftsartikel (refereegranskat)abstract
- This paper outlines promising avenues for empirical research on quantified control in healthcare work. A review of key insights from accounting, organization studies, and the emergent sociology of quantification indicates that numbers are productive as well as deceptive and seductive, that they enable control but can be evaded, and that they typically have unintended effects. It remains to be further explored how multiple forms of measurement and quantified control play out in everyday healthcare work. Other questions worth probing concern the limits and capabilities of numbers as a shared language, the differential and disciplinary effects of numbers on social groups, the use of numbers for impression management, and how people manage to resist or mobilize numbers for different purposes. Calling for additional qualitative, close-up studies, the paper proposes a research focus on everyday practices and the interactions of diverse control measures. It sets out several fruitful methodological pathways, both the well-established approaches of ethnography and Actor-Network Theory and the more novel approaches of investigating numbers as communicative acts or as dramaturgical performances.
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| 15. |
- Lövfors, William, 1991-, et al.
(författare)
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A comprehensive mechanistic model of adipocyte signaling with layers of confidence
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Adipocyte cellular signaling, normally and in type 2 diabetes, is far from fully studied. We have earlier developed detailed dynamic mathematical models for some well-studied, and partially overlapping, signaling pathways in adipocytes. Still, these models only cover a fraction of the total cellular response. For a broader coverage of the response, large-scale phosphoproteomic data is key. There exists such data for the insulin response of adipocytes, as well as prior knowledge on possible protein-protein interactions associated with a confidence level. However, methods to combine detailed dynamic models with large-scale data, using information about the confidence of included interactions, are lacking. In our new method, we first establish a core model by connecting our partially overlapping models of adipocyte cellular signaling with focus on: 1) lipolysis and fatty acid release, 2) glucose uptake, and 3) the release of adiponectin. We use the phosphoproteome data and prior knowledge to identify phosphosites adjacent to the core model, and then try to add the adjacent phosphosites to the model. The additions of the adjacent phosphosites is tested in a parallel, pairwise approach with low computation time. We then iteratively collect the accepted additions into a layer, and use the newly added layer to find new adjacent phosphosites. We find that the first 15 layers (60 added phosphosites) with the highest confidence can correctly predict independent inhibitor-data (70-90 % correct), and that this ability decrease when we add layers of decreasing confidence. In total, 60 layers (3926 phosphosites) can be added to the model and still keep predictive ability. Finally, we use the comprehensive adipocyte model to simulate systems-wide alterations in adipocytes in type 2 diabetes. This new method provide a tool to create large models that keeps track of varying confidence.Competing Interest StatementThe authors have declared no competing interest.
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| 16. |
- Lövfors, William, 1991-, et al.
(författare)
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A comprehensive mechanistic model of adipocyte signaling with layers of confidence
- 2023
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Ingår i: npj Systems Biology and Applications. - : Springer Nature. - 2056-7189. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Adipocyte signaling, normally and in type 2 diabetes, is far from fully understood. We have earlier developed detailed dynamic mathematical models for several well-studied, partially overlapping, signaling pathways in adipocytes. Still, these models only cover a fraction of the total cellular response. For a broader coverage of the response, large-scale phosphoproteomic data and systems level knowledge on protein interactions are key. However, methods to combine detailed dynamic models with large-scale data, using information about the confidence of included interactions, are lacking. We have developed a method to first establish a core model by connecting existing models of adipocyte cellular signaling for: (1) lipolysis and fatty acid release, (2) glucose uptake, and (3) the release of adiponectin. Next, we use publicly available phosphoproteome data for the insulin response in adipocytes together with prior knowledge on protein interactions, to identify phosphosites downstream of the core model. In a parallel pairwise approach with low computation time, we test whether identified phosphosites can be added to the model. We iteratively collect accepted additions into layers and continue the search for phosphosites downstream of these added layers. For the first 30 layers with the highest confidence (311 added phosphosites), the model predicts independent data well (70–90% correct), and the predictive capability gradually decreases when we add layers of decreasing confidence. In total, 57 layers (3059 phosphosites) can be added to the model with predictive ability kept. Finally, our large-scale, layered model enables dynamic simulations of systems-wide alterations in adipocytes in type 2 diabetes.
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