| 11. |
- Svensson, Per-Arne, 1969, et al.
(författare)
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Characterization of Brown Adipose Tissue in the Human Perirenal Depot
- 2014
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 22:8, s. 1830-1837
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo characterize brown adipose tissue (BAT) in the human perirenal adipose tissue depot. MethodPerirenal adipose tissue biopsies were obtained from 55 healthy kidney donors. Expression analysis was performed using microarray, real-time PCR, immunoblotting and immunohistochemistry. Additional studies using human stem cells were performed. ResultsUCP1 gene expression analysis revealed a large intra-individual variation in the perirenal adipose tissue biopsies. Both multi- and unilocular UCP1-positive adipocytes were detected in several of the adipose tissue samples analyzed by immunohistochemical staining. Microarray analysis identified 54 genes that were overexpressed in UCP1-positive perirenal adipose tissue. Real-time PCR analysis of BAT candidate genes revealed a set of genes that were highly correlated to UCP1 and a set of three transcription factor genes (PRDM16, PGC1, and RXR) that were highly correlated to each other. RXR displayed nuclear immunoreactivity in brown adipocytes and an increased gene expression during brown adipogenesis in human stem cells. ConclusionOur data provides the first molecular characterization of BAT in the perirenal adipose tissue depot. Furthermore, it highlights the transcription factor RXR as a new player in BAT development.
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| 12. |
- Taube, Magdalena, et al.
(författare)
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Evaluation of reference genes for gene expression studies in human brown adipose tissue.
- 2015
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Ingår i: Adipocyte. - : Informa UK Limited. - 2162-3945 .- 2162-397X. ; 4:4, s. 280-5
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Tidskriftsartikel (refereegranskat)abstract
- Human brown adipose tissue (BAT) has during the last 5 year been subjected to an increasing research interest, due to its putative function as a target for future obesity treatments. The most commonly used method for molecular studies of human BAT is the quantitative polymerase chain reaction (qPCR). This method requires normalization to a reference gene (genes with uniform expression under different experimental conditions, e.g. similar expression levels between human BAT and WAT), but so far no evaluation of reference genes for human BAT has been performed. Two different microarray datasets with samples containing human BAT were used to search for genes with low variability in expression levels. Seven genes (FAM96B, GNB1, GNB2, HUWE1, PSMB2, RING1 and TPT1) identified by microarray analysis, and 8 commonly used reference genes (18S, B2M, GAPDH, LRP10, PPIA, RPLP0, UBC, and YWHAZ) were selected and further analyzed by quantitative PCR in both BAT containing perirenal adipose tissue and subcutaneous adipose tissue. Results were analyzed using 2 different algorithms (Normfinder and geNorm). Most of the commonly used reference genes displayed acceptably low variability (geNorm M-values <0.5) in the samples analyzed, but the novel reference genes identified by microarray displayed an even lower variability (M-values <0.25). Our data suggests that PSMB2, GNB2 and GNB1 are suitable novel reference genes for qPCR analysis of human BAT and we recommend that they are included in future gene expression studies of human BAT.
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| 13. |
- Afghahi, Henri, 1966, et al.
(författare)
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Ongoing treatment with renin-angiotensin-aldosterone-blocking agents does not predict normoalbuminuric renal impairment in a general type 2 diabetes population.
- 2013
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Ingår i: Journal of diabetes and its complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 27:3, s. 229-34
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To examine the prevalence and the clinical characteristics associated with normoalbuminuric renal impairment (RI) in a general type 2 diabetes (T2D) population. METHODS: We included 94 446 patients with T2D (56% men, age 68.3±11.6years, BMI 29.6±5.3kg/m(2), diabetes duration 8.5±7.1years; means±SD) with renal function (serum creatinine) reported to the Swedish National Diabetes Register (NDR) in 2009. RI was defined as estimated glomerular filtration (eGFR)<60ml/min/1.73m(2) and albuminuria as a urinary albumin excretion rate (AER)>20μg/min. We linked the NDR to the Swedish Prescribed Drug Register, and the Swedish Cause of Death and the Hospital Discharge Register to evaluate ongoing medication and clinical outcomes. RESULTS: 17% of the patients had RI, and 62% of these patients were normoalbuminuric. This group of patients had better metabolic control, lower BMI, lower systolic blood pressure and were more often women, non-smokers and more seldom had a history of cardiovascular disease as compared with patients with albuminuric RI. 28% of the patients with normoalbuminuric RI had no ongoing treatment with any RAAS-blocking agent. Retinopathy was most common in patients with RI and albuminuria (31%). CONCLUSIONS: The majority of patients with type 2 diabetes and RI were normoalbuminuric despite the fact that 25% of these patients had no ongoing treatment with RAAS-blocking agents. Thus, RI in many patients with type 2 diabetes is likely to be caused by other factors than diabetic microvascular disease and ongoing RAAS-blockade.
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| 14. |
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| 15. |
- Ahmed, Fozia, et al.
(författare)
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Role of Estrogen and Its Receptors in Adipose Tissue Glucose Metabolism in Pre- and Postmenopausal Women
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 107:5, s. E1879-E1889
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Tidskriftsartikel (refereegranskat)abstract
- Context: Reduced estrogen levels in postmenopausal women predispose them to metabolic side effects, including insulin resistance and type 2 diabetes; however, the cellular mechanisms are not well understood.Objective: This work aimed to study the expression of estrogen receptors in adipose tissue from pre- and postmenopausal women and the effects of estradiol (E2) on glucose uptake of adipocytes.Methods: Subcutaneous (SAT) and visceral adipose tissue (VAT) obtained from pre- and postmenopausal women (19-51 and 46-75 years old, respectively) were used to measure gene expression of ESR1 and ESR2. SAT tissue was incubated with E2, and glucose uptake and estrogen receptor levels were measured. Polymorphisms in ESR1 and ESR2 were addressed in public databases to identify single nucleotide polymorphisms associated with metabolic traits.Results: ESR2 expression was lower in pre- vs postmenopausal women, corresponding to lower ESR1:ESR2 gene expression ratio in postmenopausal women. In premenopausal women, the expression of ESR1 was higher in VAT than in SAT. In both pre- and postmenopausal women, ESR2 expression was lower in VAT than in SAT. In late, but not pre- or early postmenopausal women, E2 reduced glucose uptake and GLUT4 protein and increased expression of ESR2. ESR1 polymorphisms were associated with weight, body fat distribution, and total cholesterol, and ESR2 polymorphisms were associated with total cholesterol and triglyceride levels and with body fat percentage.Conclusion: E2 inhibits glucose utilization in human adipocytes in late postmenopausal women. Changes in glucose utilization over time since menopause may be explained by a lower ESR1:ESR2 ratio. This can have clinical implications on the timing of estrogen treatment in postmenopausal women.
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| 16. |
- Alsterholm, Mikael, 1977, et al.
(författare)
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Establishment and utility of SwedAD : a nationwide Swedish registry for patients with atopic dermatitis receiving systemic pharmacotherapy
- 2023
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 103
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Tidskriftsartikel (refereegranskat)abstract
- SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.
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| 17. |
- Banefelt, Jonas, et al.
(författare)
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Statin dose titration patterns and subsequent major cardiovascular events in very high-risk patients: estimates from Swedish population-based registry data.
- 2020
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Ingår i: European heart journal. Quality of care & clinical outcomes. - : Oxford University Press (OUP). - 2058-1742 .- 2058-1742 .- 2058-5225. ; 6:4, s. 323-331
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Tidskriftsartikel (refereegranskat)abstract
- Clinical studies have demonstrated the efficacy of intensive statin therapy in lowering low-density lipoprotein cholesterol and cardiovascular (CV) events. Our objective was to examine statin titration patterns and the association between titration patterns and subsequent CV events in very high-risk patients.Using Swedish national population-based registry data, we identified 192435 patients with very high risk of atherosclerotic CV disease initiated on moderate-intensity statin therapy between 2006 and 2013. Outcomes of interest were titration to high-intensity therapy and the major adverse cardiovascular events (MACE) composite (myocardial infarction, ischaemic stroke, and CV death) outcome. Cumulative incidence of MACE was assessed by titration status 1-year post-treatment initiation in patients adherent to treatment during the first year, using a 12-week cut-off from initiation to define early, delayed and no up-titration to high-intensity statins. Cox regression analysis was used to estimate adjusted hazard ratios (HRs). In 144498 eligible patients, early titration was associated with significantly lower risk of MACE in the subsequent 2 years compared to no up-titration (HR 0.76, P<0.01]. Delayed up-titration was associated with a smaller reduction (HR 0.88, P=0.08). The majority of patients did not up-titrate.Early up-titration to high-intensity statins was independently associated with lower risk of subsequent CV events compared to no up-titration. Delayed up-titration was not associated with the same benefit. Despite the higher risk associated with no up-titration, few patients at very high CV risk who started treatment on moderate-intensity up-titrated to high intensity, indicating a potential need for more aggressive lipid management of these patients in clinical practice.
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| 18. |
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| 19. |
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| 20. |
- Fields, James K., et al.
(författare)
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Antibodies targeting the shared cytokine receptor IL-1 receptor accessory protein invoke distinct mechanisms to block all cytokine signaling
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Ingår i: Cell Reports. - 2211-1247.
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-1 (IL-1)-family cytokines are potent modulators of inflammation, coordinating a vast array of immunological responses across innate and adaptive immune systems. Dysregulated IL-1-family cytokine signaling, however, is involved in a multitude of adverse health effects, such as chronic inflammatory conditions, autoimmune diseases, and cancer. Within the IL-1 family of cytokines, six—IL-1α, IL-1β, IL-33, IL-36α, IL-36β, and IL-36γ—require the IL-1 receptor accessory protein (IL-1RAcP) as their shared co-receptor. Common features of cytokine signaling include redundancy of signaling pathways, sharing of cytokines and receptors, pleiotropy of the cytokines themselves, and multifaceted immune responses. Accordingly, targeting multiple cytokines simultaneously is an emerging therapeutic strategy and can provide advantages over targeting a single cytokine pathway. Here, we show that two monoclonal antibodies, CAN10 and 3G5, which target IL-1RAcP for broad blockade of all associated cytokines, do so through distinct mechanisms and provide therapeutic opportunities for the treatment of inflammatory diseases.
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