| 1. |
- Magnusson, Björn, 1976, et al.
(author)
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Cell death-inducing DFF45-like effector C is reduced by caloric restriction and regulates adipocyte lipid metabolism.
- 2008
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In: Metabolism: clinical and experimental. - : Elsevier BV. - 1532-8600. ; 57:9, s. 1307-13
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Journal article (peer-reviewed)abstract
- Members of the cell death-inducing DFF45-like effector (CIDE) gene family have been shown to regulate lipid metabolism. In this article, we report that the third member of the human CIDE family, CIDEC, is down-regulated in response to a reduced caloric intake. The down-regulation was demonstrated by microarray and real-time polymerase chain reaction analysis of subcutaneous adipose tissue in 2 independent studies on obese patients undergoing treatment with a very low calorie diet. By analysis of CIDEC expression in 65 human tissues, we conclude that human CIDEC is predominantly expressed in subcutaneous adipocytes. Together, these observations led us to investigate the effect of decreased CIDEC expression in cultured 3T3-L1 adipocytes. Small interfering RNA-mediated knockdown of CIDEC resulted in an increased basal release of nonesterified fatty acids, decreased responsiveness to adrenergic stimulation of lipolysis, and increased oxidation of endogenous fatty acids. Thus, we suggest that CIDEC is a regulator of adipocyte lipid metabolism and may be important for the adipocyte to adapt to changes in energy availability.
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| 2. |
- Behre, Carl Johan, 1968, et al.
(author)
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Dissociation between adipose tissue expression and serum levels of adiponectin during and after diet-induced weight loss in obese subjects with and without the metabolic syndrome
- 2007
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In: Metabolism: Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 56:8, s. 1022-8
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Journal article (peer-reviewed)abstract
- The study aimed to examine if dysmetabolic subjects (MetS+) have lower adiponectin gene expression and lower circulating adiponectin levels than non-dysmetabolic obese subjects (MetS-) at baseline, if adiponectin expression and adiponectin concentration rise more in the dysmetabolic group during weight loss, and if v-SNARE Vti1a (vesicle transport soluble NSF attachment protein receptor vps10p tail interacting 1a) expression increases during the weight loss, as a mechanism for increased adiponectin secretion. Twenty-one obese MetS+ and 19 obese MetS- subjects underwent a very low-energy diet for 16 weeks followed by 2 weeks of refeeding. Abdominal subcutaneous adipose tissue biopsies and blood samples were taken before, during, and after dieting for DNA microarray, reverse transcriptase-polymerase chain reaction, and biochemical analyses. Serum adiponectin was also assessed in a sex- and age-matched healthy, nonobese reference group. Weight decreased by 26.3+/-9.8 kg in the MetS+ group and 28.2+/-8.4 kg in the MetS- group with concomitant reductions in insulin, hemoglobin A1c, and triglycerides that were more pronounced in the MetS+ group. Initially, the MetS+ subjects had lower serum adiponectin, but the differences disappeared at week 8, with a continuous increase in serum adiponectin throughout the study in both groups to a level that was higher than in the reference group. The expression of adiponectin and v-SNARE Vti1a did not differ between the groups or over time. In conclusion, obese subjects with the metabolic syndrome had lower circulating adiponectin than subjects without the syndrome. Weight loss increased serum levels of adiponectin without a parallel increase in adiponectin gene expression. The mechanisms involved in the regulation of adiponectin levels merits further investigation.
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| 3. |
- Ekman, Inger, 1952, et al.
(author)
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Can treatment with ACE-inhibitors in elderly patients with moderate to severe heart failure be improved by a nurse-monitored structured care program?
- 2003
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In: Heart & Lung. - 0147-9563. ; 32:1, s. 3-9
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Journal article (peer-reviewed)abstract
- Can treatment with angiotensin-converting enzyme inhibitors in elderly patients with moderate to severe chronic heart failure be improved by a nurse-monitored structured care program? A randomized controlled trial. OBJECTIVE: The purpose of this study was to examine whether a nurse-monitored structured care program resulted in a more effective use of angiotensin-converting enzyme (ACE) inhibitors in elderly patients compared with standard care in patients with chronic heart failure (CHF). METHODS: Hospitalized patients were screened to identify individuals with CHF, age more than 65 years, New York Heart Association classification III to IV, and no contraindications to ACE inhibitor treatment. One hundred forty-five patients were randomized to a nurse-monitored structured care program that included uptitration of enalapril to a target dose of 10 mg twice a day or to standard care. Six-month follow-up data were collected. RESULTS: The mean age of the randomized patients was 81 years. Although the proportion of patients treated with an ACE inhibitor did not differ between structured care (70%) and standard care (64%), the number of patients with the target ACE inhibitor dose was significantly higher in the structured care group (26% versus 11% in the standard care group; P <.018). Treatment had to be discontinued in 26% of the patients because of adverse effects. CONCLUSION: The patients in this study were older than in previous intervention studies and had considerable comorbidity and reduced tolerance for ACE inhibitors. ACE inhibitor treatment was underused but improved with the structured care program, although achieved treatment levels were below those in the large intervention trials in patients with CHF.
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| 4. |
- Englund, Katarina, et al.
(author)
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Beslutsstöd gav bättre diagnostik och vård av barn med fetma. : Decision support system improved the care of children and adolescents with obesity
- 2013
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In: Läkartidningen. - 0023-7205. ; 110:23-24, s. 1165-7
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Journal article (peer-reviewed)abstract
- Ett webbaserat beslutsstöd för hälsofrämjande, förebyggande och behandlande insatser mot fetma bland barn och vuxna har utvecklats i Västra Götalandsregionen. Eventuella förändringar i omhändertagandet vid barn- och ungdomsmedicinska mottagningar av detta utvärderades. Vid samtliga mottagningar vägdes och mättes barn i större utsträckning 2011 än 2005, och fetmadiagnosen baserades oftast på BMI-uträkning. Andelen barn och ungdomar som fått diagnosen fetma mer än fördubblades under perioden 2005–2011. Fler barnmottagningar och fler yrkesgrupper deltog 2011 i vården av barn med fetma. Trots det var det fortfarande en majoritet av barnen och ungdomarna med fetma som inte uppmärksammades av hälso- och sjukvården.
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| 5. |
- Gummesson, Anders, 1973, et al.
(author)
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Intestinal Permeability Is Associated With Visceral Adiposity in Healthy Women.
- 2011
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In: Obesity (Silver Spring, Md.). - : Wiley. - 1930-7381.
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Journal article (peer-reviewed)abstract
- Increased visceral fat, as opposed to subcutaneous/gluteal, most strongly relates to key metabolic dysfunctions including insulin resistance, hepatic steatosis, and inflammation. Mesenteric fat hypertrophy in patients with Crohn's disease and in experimental rodent models of gut inflammation suggest that impaired gut barrier function with increased leakage of gut-derived antigens may drive visceral lipid deposition. The aim of this study was to determine whether increased intestinal permeability is associated with visceral adiposity in healthy humans. Normal to overweight female subjects were recruited from a population-based cohort. Intestinal permeability was assessed using the ratio of urinary excretion of orally ingested sucralose to mannitol (S/M). In study 1 (n = 67), we found a positive correlation between waist circumference and S/M excretion within a time frame of urine collection consistent with permeability of the lower gastrointestinal tract (6-9 hours post-ingestion; P = 0.022). These results were followed up in study 2 (n = 55) in which we used computed tomography and dual energy X-ray absorptiometry to measure visceral and subcutaneous fat areas of the abdomen, liver fat content, and total body fat of the same women. The S/M ratio from the 6-12 h urine sample correlated with visceral fat area (P = 0.0003) and liver fat content (P = 0.004), but not with subcutaneous or total body fat. This novel finding of an association between intestinal permeability and visceral adiposity and liver fat content in healthy humans suggests that impaired gut barrier function should be further explored as a possible mediator of excess visceral fat accumulation and metabolic dysfunction.
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| 6. |
- Gummesson, Anders, 1973, et al.
(author)
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Relations of Adipose Tissue Cell Death-Inducing DFFA-like Effector A Gene Expression to Basal Metabolic Rate, Energy Restriction and Obesity: Population-based and Dietary Intervention Studies.
- 2007
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:12, s. 4759-65
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Journal article (peer-reviewed)abstract
- Context: Cell death-inducing DFFA-like effector A (CIDEA) could be a potential target for the treatment of obesity via the modulation of metabolic rate, based on the findings that CIDEA inhibits the brown adipose tissue uncoupling process in rodents. Objective: To investigate the putative link between CIDEA and basal metabolic rate in humans, and to further elucidate the role of CIDEA in human obesity. Design: We have explored CIDEA gene expression in adipose tissue in two different human studies: A cross-sectional and population-based study assessing body composition and metabolic rate (Mölndal Metabolic study, n=92), and a longitudinal intervention-study of obese subjects treated with a very low calorie diet (VLCD study, n=24). Results: The CIDEA gene was predominantly expressed in adipocytes as compared to other human tissues. CIDEA gene expression in adipose tissue was inversely associated with basal metabolic rate independently of body composition, age and gender (p=0.014). VLCD induced an increase in adipose tissue CIDEA expression (p<0.0001) with a subsequent decrease in response to refeeding (p<0.0001). Reduced CIDEA gene expression was associated with a high body fat content (p<0.0001) and with high insulin levels (p<0.01). No dysregulation of CIDEA expression was observed in individuals with the metabolic syndrome when compared with BMI-matched controls. In a separate sample of VLCD-treated subjects (n=10), uncoupling protein 1 expression was reduced during diet (p=0.0026) and inversely associated with CIDEA expression (p=0.0014). Conclusion: The findings are consistent with the concept that CIDEA plays a role in adipose tissue energy expenditure.
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| 7. |
- Hägg, Daniel, 1974, et al.
(author)
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Expression profiling of macrophages from subjects with atherosclerosis to identify novel susceptibility genes.
- 2008
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In: International journal of molecular medicine. - 1107-3756. ; 21:6, s. 697-704
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Journal article (peer-reviewed)abstract
- Although a number of environmental risk factors for atherosclerosis have been identified, heredity seems to be a significant independent risk factor. The aim of our study was to identify novel susceptibility genes for atherosclerosis. The screening process consisted of three steps. First, expression profiles of macrophages from subjects with atherosclerosis were compared to macrophages from control subjects. Secondly, the subjects were genotyped for promoter region polymorphisms in genes with altered gene expression. Thirdly, a population of subjects with coronary heart disease and control subjects were genotyped to test for an association with identified polymorphisms that affected gene expression. Twenty-seven genes were differentially expressed in both macrophages and foam cells from subjects with atherosclerosis. Three of these genes, IRS2, CD86 and SLC11A1 were selected for further analysis. Foam cells from subjects homozygous for the C allele at the -765C-->T SNP located in the promoter region of IRS2 had increased gene expression compared to foam cells from subjects with the nonCC genotype. Also, macrophages and foam cells from subjects homozygous for allele 2 at a repeat element in the promoter region of SLC11A1 had increased gene expression compared to macrophages and foam cells from subjects with the non22 genotype. Genotyping of 512 pairs of subjects with coronary heart disease (CHD) and matched controls revealed that subjects homozygous for C of the IRS2 SNP had an increased risk for CHD; odds ratio 1.43, p=0.010. Immunohistochemical staining of human carotid plaques showed that IRS2 expression was localised to macrophages and endothelial cells in vivo. Our method provides a reliable approach for identifying susceptibility genes for atherosclerosis, and we conclude that elevated IRS2 gene expression in macrophages may be associated with an increased risk of CHD.
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| 8. |
- Sachdev, P. S., et al.
(author)
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STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease
- 2017
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 7, s. 11-23
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Journal article (peer-reviewed)abstract
- Introduction The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). Methods Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. Results Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3months to 21years. Discussion Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes. © 2016 The Authors
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| 9. |
- Svensson, Per Anders, 1959, et al.
(author)
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Identification of genes predominantly expressed in human macrophages
- 2004
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In: Atherosclerosis. - : Elsevier BV. ; 177, s. 287-290
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Journal article (peer-reviewed)abstract
- Identification of cell and tissue specific genes may provide novel insights to signaling systems and functions. Macrophages play a key role in many diseases including atherosclerosis. Using DNA microarrays we compared the expression of approximately 10,000 genes in 56 human tissues and identified 23 genes with predominant expression in macrophages. The identified genes include both genes known to be macrophage specific and genes previously not well described in this cell type. Tissue distribution of two genes, liver X receptor (LXR) alpha and interleukin-1 receptor antagonist (IL1RN), was verified by real-time RT-PCR. We conclude that comparison of expression profiles from a large number of tissues can be used to identify genes that are predominantly expressed in certain tissues. Identification of novel macrophage specific genes may increase our understanding of the role of this cell in different diseases.
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| 10. |
- Svensson, Per-Arne, 1969, et al.
(author)
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Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques
- 2005
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In: BMC Cardiovasc Disord. - : Springer Science and Business Media LLC. - 1471-2261. ; 5
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Journal article (peer-reviewed)abstract
- BACKGROUND: The protective role of high-density lipoprotein (HDL) in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI) binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans. The aim of this study was to investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques. METHODS: The effect of hypoxia and minimally modified low-density lipoprotein (mmLDL), two proatherogenic stimuli, on SR-BI expression was studied in human monocyte-derived macrophages from healthy subjects using real-time PCR. In addition, SR-BI expression was determined in macrophages obtained from subjects with atherosclerosis (n = 15) and healthy controls (n = 15). Expression of SR-BI isoforms was characterized in human atherosclerotic plaques and macrophages using RT-PCR and DNA sequencing. RESULTS: SR-BI expression was decreased in macrophages after hypoxia (p < 0.005). In contrast, SR-BI expression was increased by exposure to mmLDL (p < 0.05). There was no difference in SR-BI expression in macrophages from patients with atherosclerosis compared to controls. In both groups, SR-BI expression was increased by exposure to mmLDL (p < 0.05). Transcripts corresponding to SR-BI and SR-BII were detected in macrophages. In addition, a third isoform, referred to as SR-BIII, was discovered. All three isoforms were also expressed in human atherosclerotic plaque. Compared to the other isoforms, the novel SR-BIII isoform was predicted to have a unique intracellular C-terminal domain containing 53 amino acids. CONCLUSION: We conclude that SR-BI is regulated by proatherogenic stimuli in humans. However, we found no differences between subjects with atherosclerosis and healthy controls. This indicates that altered SR-BI expression is not a common cause of atherosclerosis. In addition, we identified SR-BIII as a novel isoform expressed in human macrophages and in human atherosclerotic plaques.
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