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Sökning: LAR1:gu > Tidskriftsartikel > Refereegranskat > Sjöström Lars > Jacobson Peter 1962

  • Resultat 1-10 av 28
  • [1]23Nästa
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1.
  • Ahlin, Sofie, 1985-, et al. (författare)
  • Macrophage Gene Expression in Adipose Tissue is Associated with Insulin Sensitivity and Serum Lipid Levels Independent of Obesity.
  • 2013
  • Ingår i: Obesity (Silver Spring, Md.). - 1930-739X. ; 21:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Obesity is linked to both increased metabolic disturbances and increased adipose tissue macrophage infiltration. However, whether macrophage infiltration directly influences human metabolism is unclear. The aim of this study was to investigate if there are obesity-independent links between adipose tissue macrophages and metabolic disturbances. Design and Methods: Expression of macrophage markers in adipose tissue was analyzed by DNA microarrays in the SOS Sib Pair study and in patients with type 2 diabetes and a BMI-matched healthy control group. Results: The expression of macrophage markers in adipose tissue was increased in obesity and associated with several metabolic and anthropometric measurements. After adjustment for BMI, the expression remained associated with insulin sensitivity, serum levels of insulin, C-peptide, high density lipoprotein cholesterol (HDL-cholesterol) and triglycerides. In addition, the expression of most macrophage markers was significantly increased in patients with type 2 diabetes compared to the control group. Conclusion: Our study shows that infiltration of macrophages in human adipose tissue, estimated by the expression of macrophage markers, is increased in subjects with obesity and diabetes and associated with insulin sensitivity and serum lipid levels independent of BMI. This indicates that adipose tissue macrophages may contribute to the development of insulin resistance and dyslipidemia.
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2.
  • Anveden, Åsa, et al. (författare)
  • ITIH-5 Expression in Human Adipose Tissue Is Increased in Obesity.
  • 2012
  • Ingår i: Obesity. - 1930-7381. ; 20:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Adipocytes secrete many proteins that regulate metabolic functions. The gene inter-α (globulin) inhibitor H5 (ITIH-5) encodes a secreted protein and is known to be expressed abundantly in the placenta. However, using gene expression profiles data we observed high expression of ITIH-5 in adipose tissue. The aim of this study was to test the hypothesis that ITIH-5 is strongly expressed in human adipocytes and adipose tissue, and is related to obesity and clinical metabolic variables. ITIH-5 adipose tissue mRNA expression was analyzed with DNA microarray and real-time PCR, and its association with clinical variables was examined. ITIH-5 protein expression was analyzed using western blot. ITIH-5 mRNA expression was abundant in human adipose tissue, adipocytes, and placenta, and higher in subcutaneous (sc) compared to omental adipose tissue (P < 0.0001). ITIH-5 mRNA and protein expression in sc adipose tissue were higher in obese compared to lean subjects (P < 0.0001 and P < 0.001, respectively). ITIH-5 mRNA expression was reduced after diet-induced weight loss (P < 0.0001). ITIH-5 mRNA expression was associated with anthropometry and clinical metabolic variables. In conclusion, ITIH-5 is highly expressed in sc adipose tissue, increased in obesity, down regulated after weight loss, and associated with measures of body size and metabolism. Together, this indicates that ITIH-5 merits further investigation as a regulator of human metabolism.
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3.
  • Burza, Maria A, et al. (författare)
  • PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals
  • 2012
  • Ingår i: Digestive and Liver Disease. - 1590-8658. ; 44:12, s. 1037-1041
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Obesity is a risk factor for cancer, including hepatocellular carcinoma. Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) genetic variant has been associated with hepatocellular carcinoma (HCC) in individuals with chronic alcohol abuse or hepatic viral infection. In the present study we examined the association between the PNPLA3I148M genetic variant and hepatocellular carcinoma in obese individuals from the Swedish Obese Subjects cohort (n=4047). Methods: We performed a matched, prospective, controlled, interventional trial, investigating the effect of bariatric surgery (surgery group) compared to conventional treatment (control group) for obesity. Results: A total of 9 events were observed in the 15-year median follow up (5 in the control group and 4 in the surgery group). A significantly higher incidence of hepatocellular carcinoma in PNPLA3 148M allele carriers was found in obese individuals in the control group (log-rank P-value=0.001), but not in the surgery group (log-rank P-value=0.783). Consistently, an increased risk (for each PNPLA3 148M allele, hazard ratio: 5.9; 95% confidence interval 1.5-23.8; P-value=0.013) of developing hepatocellular carcinoma was observed only in the control group. Conclusion: The current study is the first prospective report showing the association of the PNPLA3I148M genetic variant and hepatocellular carcinoma in severely obese individuals.
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4.
  • Carlsson, Lena M S, 1957-, et al. (författare)
  • ALK7 expression is specific for adipose tissue, reduced in obesity and correlates to factors implicated in metabolic disease.
  • 2009
  • Ingår i: Biochemical and biophysical research communications. - 1090-2104. ; 382:2, s. 309
  • Tidskriftsartikel (refereegranskat)abstract
    • Human adipose tissue is a major site of expression of inhibin beta B (INHBB) which homodimerizes to form the novel adipokine activin B. Our aim was to determine if molecules needed for a local action of activin B are expressed in adipose tissue. Microarray analysis showed that adipose tissue expressed activin type I and II receptors and that the expression of activin receptor-like kinase 7 (ALK7) was adipose tissue specific. In obesity discordant siblings from the SOS Sib Pair study, adipose tissue ALK7 expression was higher in lean (n=90) compared to obese (n=90) subjects (p=4 x 10(-31)). Adipose tissue ALK7 expression correlated with several measures of body fat, carbohydrate metabolism and lipids. In addition, ALK7 and INHBB expression correlated but only in lean subjects and in subjects with normal glucose tolerance. We conclude that activin B may have local effects in adipose tissue and thereby influence obesity and its comorbidities.
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5.
  • Clark, Stephen J, et al. (författare)
  • Association of Sirtuin 1 (SIRT1) Gene SNPs and Transcript Expression Levels With Severe Obesity.
  • 2012
  • Ingår i: Obesity. - 1930-7381. ; 20:1, s. 178-85
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies have reported associations of sirtuin 1 (SIRT1) single nucleotide polymorphisms (SNPs) to both obesity and BMI. This study was designed to investigate association between SIRT1 SNPs, SIRT1 gene expression and obesity. Case-control analyses were performed using 1,533 obese subjects (896 adults, BMI >40 kg/m(2) and 637 children, BMI >97th percentile for age and sex) and 1,237 nonobese controls, all French Caucasians. Two SNPs (in high linkage disequilibrium (LD), r(2) = 0.96) were significantly associated with adult obesity, rs33957861 (P value = 0.003, odds ratio (OR) = 0.75, confidence interval (CI) = 0.61-0.92) and rs11599176 (P value: 0.006, OR = 0.74, CI = 0.61-0.90). Expression of SIRT1 mRNA was measured in BMI-discordant siblings from 154 Swedish families. Transcript expression was significantly correlated to BMI in the lean siblings (r(2) = 0.13, P value = 3.36 × 10(-7)) and lower SIRT1 expression was associated with obesity (P value = 1.56 × 10(-35)). There was also an association between four SNPs (rs11599176, rs12413112, rs33957861, and rs35689145) and BMI (P values: 4 × 10(-4), 6 × 10(-4), 4 × 10(-4), and 2 × 10(-3)) with the rare allele associated with a lower BMI. However, no SNP was associated with SIRT1 transcript expression level. In summary, both SNPs and SIRT1 gene expression are associated with severe obesity.
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6.
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7.
  • Jacobson, Peter, 1962-, et al. (författare)
  • Melanocortin 4 receptor sequence variations are seldom a cause of human obesity: the Swedish Obese Subjects, the HERITAGE Family Study, and a Memphis cohort.
  • 2002
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 87:10, s. 4442-6
  • Tidskriftsartikel (refereegranskat)abstract
    • The prevalence of mutations within and in the flanking regions of the gene encoding the melanocortin 4 receptor was investigated in severely obese and normal-weight subjects from the Swedish Obese Subjects study, the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family study, and a Memphis cohort. A total of 433 white and 95 black subjects (94% females) were screened for mutations by direct sequencing. Three previously described missense variants and nine novel (three missense, six silent) variants were detected. None of them showed significant association with obesity or related phenotypes. In addition, two novel deletions were found in two heterozygous obese women: a -65_-64delTG mutation within the 5' noncoding region and a 171delC frameshift mutation predicted to result in a truncated nonfunctional receptor. No pathogenic mutations were found among obese blacks or nonobese controls. Furthermore, none of the null mutations found in other populations was present in this sample. In conclusion, our results do not support the prevailing notion that sequence variation in the melanocortin 4 receptor gene is a frequent cause of human obesity.
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8.
  • Jacobson, Peter, 1962-, et al. (författare)
  • Spouse resemblance in body mass index: effects on adult obesity prevalence in the offspring generation.
  • 2007
  • Ingår i: American journal of epidemiology. - 0002-9262. ; 165:1, s. 101-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Accruing evidence indicates that mate selection is promoted by similarity in body fatness. Assortative mating for obesity may contribute genetically to the obesity epidemic by increasing the risk in subsequent generations. To test this hypothesis, the authors analyzed measured and validated questionnaire data on family members, obtained between 1987 and 2000 from 7,834 obese probands and from 829 subjects randomly ascertained from the general Swedish population. Spouse correlations in body mass index were strongest among couples with the shortest duration of cohabitation. Obesity concordance in parents was associated with an obesity prevalence of 20.1% in adult offspring compared with 1.4% if parents were concordantly nonobese (odds ratio = 18.3, 95% confidence interval: 9.0, 37.4). The prevalence was 8.2% if parents were obesity discordant (odds ratio = 6.5, 95% confidence interval: 3.2, 13.2). No association was found between rearing parents' and nonbiologic offspring's body mass index. These results agree with the hypothesis that assortative mating for obesity confers a higher risk of obesity in the offspring generation and thus contributes to the obesity epidemic. Parental obesity concordance is a strong, easily identifiable genetic risk factor that should be considered in the complex network of risk factors for obesity in designing primary prevention programs.
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9.
  • Jernås, Margareta, 1961-, et al. (författare)
  • Regulation of carboxylesterase 1 (CES1) in human adipose tissue.
  • 2009
  • Ingår i: Biochemical and biophysical research communications. - 1090-2104. ; 383:1, s. 63-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Carboxylesterase 1 (CES1) has recently been suggested to play a role in lipolysis. Our aim was to study the regulation of CES1 expression in human adipose tissue. In the SOS Sib Pair Study, CES1 expression was higher in obese compared with lean sisters (n=78 pairs, P=8.7x10(-18)) and brothers (n=12 pairs, P=0.048). CES1 expression was higher in subcutaneous compared with omental adipose tissue in lean (P=0.027) and obese subjects (P=0.00036), and reduced during diet-induced weight loss (n=24, weeks 8, 16, and 18 compared to baseline, P<0.0001 for all time points). CES1 expression was higher in isolated adipocytes compared with intact adipose tissue (P=0.0018) and higher in large compared with small adipocytes (P=4.1x10(-6)). Basal and stimulated lipolysis was not different in individuals with high, intermediate, and low expression of CES1. Thus, CES1 expression was linked to body fat and adipocyte fat content but not to lipolytic activity.
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10.
  • Moustafa, J. S. E., et al. (författare)
  • Novel association approach for variable number tandem repeats (VNTRs) identifies DOCK5 as a susceptibility gene for severe obesity
  • 2012
  • Ingår i: Human Molecular Genetics. - 0964-6906. ; 21:16, s. 3727-3738
  • Tidskriftsartikel (refereegranskat)abstract
    • Variable number tandem repeats (VNTRs) constitute a relatively under-examined class of genomic variants in the context of complex disease because of their sequence complexity and the challenges in assaying them. Recent large-scale genome-wide copy number variant mapping and association efforts have highlighted the need for improved methodology for association studies using these complex polymorphisms. Here we describe the in-depth investigation of a complex region on chromosome 8p21.2 encompassing the dedicator of cytokinesis 5 (DOCK5) gene. The region includes two VNTRs of complex sequence composition which flank a common 3975 bp deletion, all three of which were genotyped by polymerase chain reaction and fragment analysis in a total of 2744 subjects. We have developed a novel VNTR association method named VNTRtest, suitable for association analysis of multi-allelic loci with binary and quantitative outcomes, and have used this approach to show significant association of the DOCK5 VNTRs with childhood and adult severe obesity (P-empirical 8.9 10(8) and P 3.1 10(3), respectively) which we estimate explains approximate to 0.8 of the phenotypic variance. We also identified an independent association between the 3975 base pair (bp) deletion and obesity, explaining a further 0.46 of the variance (P-combined 1.6 10(3)). Evidence for association between DOCK5 transcript levels and the 3975 bp deletion (P 0.027) and both VNTRs (P-empirical 0.015) was also identified in adipose tissue from a Swedish family sample, providing support for a functional effect of the DOCK5 deletion and VNTRs. These findings highlight the potential role of DOCK5 in human obesity and illustrate a novel approach for analysis of the contribution of VNTRs to disease susceptibility through association studies.
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