| 1. |
- de Man Lapidoth, Julia, et al.
(författare)
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Trends in renal function in Northern Sweden 1986-2014 : data from the seven cross-sectional surveys within the Northern Sweden MONICA study
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The prevalence of chronic kidney disease (CKD) is increasing globally, and CKD is closely related to cardiovascular disease (CVD). CKD and CVD share several risk factors (RF), such as diabetes, hypertension, obesity and smoking, and the prevalence of these RF has changed during the last decades, and we aimed to study the effect on renal function over time.Design: Repeated cross-sectional population-based studies.Setting: The two Northern counties (Norr- and Vasterbotten) in Sweden.Participants: Within the MONitoring Trends and Determinants of CArdiovascular Disease (MONICA) study, seven surveys were performed between 1986 and 2014, including participants aged 25-64 years (n=10 185).Interventions: None.Measures: Information on anthropometry, blood pressure and cardiovascular risk factors was collected. Creatinine and cystatin C were analysed in stored blood samples and the estimated glomerular filtration rate (eGFR) calculated using the creatinine-based Lund-Malmo revised and Chronic Kidney Disease Epidemiology Collaboration (eGFR(crea)) equations as well as the cystatin C-based Caucasian, Asian, Paediatric and Adult cohort (CAPA) equation (eGFR(cysC)). Renal function over time was analysed using univariable and multivariable linear regression models.Results: Renal function, both eGFR(crea) and eGFR(cysC), decreased over time (both p<0.001) and differed between counties and sexes. In a multivariable analysis, study year remained inversely associated with both eGFR(crea) and eGFR(cysC) (both p<0.001) after adjustment for classical cardiovascular RF.Conclusion: Renal function has deteriorated in Northern Sweden between 1986 and 2014.
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| 2. |
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| 3. |
- 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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| 4. |
- Lindh, Maria, et al.
(författare)
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Cardiovascular event rates in a high atherosclerotic cardiovascular disease risk population : estimates from Swedish population-based register data
- 2019
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : OXFORD UNIV PRESS. - 2058-5225 .- 2058-1742. ; 5:3, s. 225-232
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study aimed to estimate the rate of cardiovascular (CV) events in the real world in patients at high risk of recurrent CV events similar to the FOURIER trial population.Methods and results: A retrospective population-based cohort study was conducted using Swedish national registers from 1 July 2001 to 31 December 2015. Patients in the atherosclerotic cardiovascular disease (ASCVD) prevalent cohort met the FOURIER-like inclusion criteria, including treatment with high/moderate-intensity statins, on 1 July 2006. Additionally, two cohorts defined by diagnosis of incident ischaemic stroke (IS) and incident myocardial infarction (MI), meeting the FOURIER-like inclusion criteria were followed from date of diagnosis. Event rates were calculated for the hard major adverse cardiovascular events (MACE) composite: MI, IS, and CV death; and the ASCVD composite: MI, IS, unstable angina, coronary revascularization, and CV death. Approximately half of patients experienced a CV event (ASCVD composite) during follow-up. The MACE composite rates/100 person-years were 6.3, 11.9, and 12.3 in the ASCVD prevalent (n = 54 992), MI incident (n = 45 895), and IS incident (n = 36 134) cohorts, respectively. The ASCVD composite rates/100 person-years were 7.0, 21.7, and 12.9 in the ASCVD prevalent, MI incident, and IS incident cohorts, respectively. The multiple-event MACE composite rates/100 person-years were 8.5 (ASCVD prevalent cohort), 15.4 (MI incident cohort), and 14.4 (IS incident cohort).Conclusion: In this real-world setting, CV event rates were high in all studied cohorts. In particular, the MACE composite rates were two to three times higher than in the FOURIER clinical trial, indicating a substantial disease burden despite treatment with moderate or high-intensity statins.
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| 5. |
- Pereira, Maria J., 1981-, et al.
(författare)
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CDKN2C expression in adipose tissue is reduced in type II diabetes and central obesity: impact on adipocyte differentiation and lipid storage?
- 2022
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Ingår i: Translational Research. - : Elsevier BV. - 1931-5244 .- 1878-1810. ; 242, s. 105-121
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Tidskriftsartikel (refereegranskat)abstract
- CDKN2C/p18 (Cyclin-Dependent Kinase Inhibitor 2C) is a cell growth regulator that controls cell cycle progression and has previously been associated with increased risk for type II diabetes (T2D) and reduced peripheral adipose tissue (AT) storage capacity. This study explored the role of CDKN2C in AT lipid and glucose metabolism in T2D. Expression of CDKN2C and other genes was analyzed by transcriptomics, or real-time PCR in subcutaneous AT (SAT) samples obtained from T2D and control subjects matched for sex, age and BMI and also in paired SAT and omental AT (OAT) samples. Functional studies included adipocyte glucose uptake and lipolysis rates. CRISPR/Cas9 CDKN2C gene knockdown was performed in human preadipocytes to assess adipogenesis. CDKN2C mRNA expression in SAT and OAT was reduced in T2D and obese subjects compared to controls. CDKN2C expression in SAT was inversely correlated with measures of hyperglycemia, insulin resistance and visceral adiposity and positively correlated with expression of genes in several metabolic pathways, including insulin signaling and fatty acid and carbohydrate metabolism. CDKN2C protein was mainly expressed in adipocytes compared to stromal vascular cells, and its gene and protein expression was up-regulated during adipocyte differentiation. Knockdown of CDKN2C did not affect the percentage of differentiating cells compared to wild type cultures. However, CDKN2C knockdown cultures had significantly lower expression of differentiation markers CEBPA, ADIPOQ and FASN and transiently reduced lipid accumulation per adipocyte during differentiation. Our findings suggest that adipose CDKN2C expression might be reduced as a consequence of insulin resistance and obesity, and this can further contribute to impairment of SAT lipid storage. © 2021 The Authors
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| 7. |
- Pereira, Maria J, 1981, et al.
(författare)
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The immunosuppressive agents rapamycin, cyclosporin A and tacrolimus increase lipolysis, inhibit lipid storage and alter expression of genes involved in lipid metabolism in human adipose tissue.
- 2013
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Ingår i: Molecular and cellular endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 365:2, s. 260-9
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Tidskriftsartikel (refereegranskat)abstract
- Cyclosporin A (CsA), tacrolimus and rapamycin are immunosuppressive agents (IAs) associated with insulin resistance and dyslipidemia, although their molecular effects on lipid metabolism in adipose tissue are unknown. We explored IAs effects on lipolysis, lipid storage and expression of genes involved on lipid metabolism in isolated human adipocytes and/or adipose tissue obtained via subcutaneous and omental fat biopsies. CsA, tacrolimus and rapamycin increased isoproterenol-stimulated lipolysis and inhibited lipid storage by 20-35% and enhanced isoproterenol-stimulated hormone-sensitive lipase Ser552 phosphorylation. Rapamycin also increased basal lipolysis (∼20%) and impaired insulin's antilipolytic effect. Rapamycin, down-regulated the gene expression of perilipin, sterol regulatory element-binding protein 1 (SREBP1) and lipin 1, while tacrolimus down-regulated CD36 and aP2 gene expression. All three IAs increased IL-6 gene expression and secretion, but not expression and secretion of TNF-α or adiponectin. These findings suggest that CsA, tacrolimus and rapamycin enhance lipolysis, inhibit lipid storage and expression of lipogenic genes in adipose tissue, which may contribute to the development of dyslipidemia and insulin resistance associated with immunosuppressive therapy.
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| 8. |
- Sidibeh, Cherno O., et al.
(författare)
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Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance
- 2017
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 55:3, s. 839-852
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Tidskriftsartikel (refereegranskat)abstract
- We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone. CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity. Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue. Subcutaneous adipose tissue was obtained from well-controlled type 2 diabetes subjects and controls. Subcutaneous adipose tissue gene expression levels of CNR1 and endocannabinoid synthesizing and degrading enzymes were assessed. Furthermore, paired human subcutaneous adipose tissue and omental adipose tissue from non-diabetic volunteers undergoing kidney donation or bariatric surgery, was incubated with or without dexamethasone. Subcutaneous adipose tissue obtained from volunteers through needle biopsy was incubated with or without dexamethasone and in the presence or absence of the CNR1-specific antagonist AM281. CNR1 gene and protein expression, lipolysis and glucose uptake were evaluated. Subcutaneous adipose tissue CNR1 gene expression levels were 2-fold elevated in type 2 diabetes subjects compared with control subjects. Additionally, gene expression levels of CNR1 and endocannabinoid-regulating enzymes from both groups correlated with markers of insulin resistance. Dexamethasone increased CNR1 expression dose-dependently in subcutaneous adipose tissue and omental adipose tissue by up to 25-fold. Dexamethasone pre-treatment of subcutaneous adipose tissue increased lipolysis rate and reduced glucose uptake. Co-incubation with the CNR1 antagonist AM281 prevented the stimulatory effect on lipolysis, but had no effect on glucose uptake. CNR1 is upregulated in states of type 2 diabetes and insulin resistance. Furthermore, CNR1 is involved in glucocorticoid-regulated lipolysis. Peripheral CNR1 could be an interesting drug target in type 2 diabetes and dyslipidemia.
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| 9. |
- 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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