| 1. |
- Li, Xiaonan, et al.
(författare)
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Adiponectin and peroxisome proliferator-activated receptor gamma expression in subcutaneous and omental adipose tissue in children
- 2008
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 97:5, s. 630-5
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To compare the expression levels of the adiponectin and peroxisome proliferator -activated receptor gamma (PPARgamma) genes in subcutaneous adipose tissue (SC) and omental adipose tissue (OM) in children with relation to age and anthropometric variables. METHODS: Paired biopsies (SC and OM) were obtained from 53 children (age 0.2-14 years, BMI 12.5-25.8 kg/m(2)). Adiponectin and PPARgamma mRNA levels in adipose tissue were measured by real-time PCR. RESULTS: In overweight, but not in normal weight children, the median adiponectin mRNA level was significantly lower in OM [0.51 (0.1-2.17)] compared to SC [1.29 (0.16-5.08)], (p = 0.03). Adiponectin mRNA levels were strongly associated with PPARgamma mRNA levels in both SC (r = 0.73, p < 0.001) and OM (r = 0.78, p < 0.001). CONCLUSIONS: The lower adiponectin expression in OM relative to SC in overweight children indicates that metabolic-endocrine alterations begin already in childhood. The close association between adiponectin and PPARgamma expression supports the hypothesis this transcription factor is involved in adiponectin gene regulation.
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| 2. |
- Li, X., et al.
(författare)
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Depot-specific messenger RNA expression of 11 beta-hydroxysteroid dehydrogenase type 1 and leptin in adipose tissue of children and adults
- 2007
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Ingår i: International Journal of Obesity. - London : Macmillan. - 0307-0565 .- 1476-5497. ; 31:5, s. 820-828
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare expression of messenger RNA (mRNA) coding for the cortisol regenerating enzyme 11-hydroxysteroid dehydrogenase type 1 (11-HSD1), and the adipocytokines leptin and resistin in paired biopsies of subcutaneous adipose tissue (SC) and omental adipose tissue (OM) from children. Design: Paired biopsies (SC and OM) were obtained from 54 children (age 0.17–16 years, body mass index (BMI) 12.5–28.3 kg/m2, BMI standard deviation score (SDS) -2.5–4.5) and 16 adults (age 27–79 years, BMI 19–46 kg/m2) undergoing open abdominal surgery. mRNA levels of 11-HSD1, leptin and resistin were measured using quantitative real-time polymerase chain reaction (PCR). Results: 11-HSD1 mRNA level was higher in OM than in SC (P<0.05), whereas leptin mRNA was higher in SC than in OM (P<0.001). There was no difference in the resistin mRNA level between SC and OM. These results were consistent in children and adults. In children, 11-HSD1 mRNA in SC was positively associated with BMI SDS (P<0.05), whereas in OM it was positively associated with age (P<0.05). The association between 11-HSD1 expression and age remained significant after adjustment for BMI SDS and gender. Leptin mRNA was positively associated with BMI SDS (SC:P<0.001, OM: P<0.001) but not with age in children. In multiple regression analyses, including anthropometric variables and age, BMI SDS was independently associated with mRNA levels of 11-HSD1 (P<0.05) and leptin (P<0.001) in SC. When normal weight and overweight children were analyzed separately, 11-HSD1 mRNA levels were positively associated with leptin in OM in the overweight group (P<0.05). Conclusion: There are depot-specific differences in mRNA levels of 11-HSD1 and leptin in children and adults. The positive association of 11-HSD1 mRNA in OM with age may reflect a causal role in visceral fat accumulation during growth. Increasing 11-HSD1 and leptin mRNA in SC with increasing BMI SDS could suggest that the risk of metabolic consequences of obesity may be established early in life.
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| 3. |
- Andersson, Eva-Lotta, et al.
(författare)
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Bile salt-stimulated lipase and pancreatic lipase-related protein 2 : key enzymes for lipid digestion in the newborn examined using the Caco-2 cell line
- 2011
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Ingår i: Journal of Lipid Research. - : American Society for Biochemistry and Molecular Biology. - 0022-2275 .- 1539-7262. ; 52:11, s. 1949-1956
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Tidskriftsartikel (refereegranskat)abstract
- In rodents, bile salt-stimulated lipase (BSSL) and pancreatic lipase-related protein 2 (PLRP2) are the dominant lipases expressed in the exocrine pancreas in early life, when milk is the main food. The aim of the present study was to evaluate if BSSL and PLRP2 are also key enzymes in neonatal intestinal fat digestion. Using Caco-2 cells as a model for the small intestinal epithelium, purified human enzymes were incubated in the apical chamber with substrates and bile salt concentrations resembling the milieu of the small intestine of newborn infants. BSSL and PLRP2 hydrolyzed triglycerides (TG) to free fatty acids (FA) and glycerol. The cells took up the FA, which were reesterfied to TG. Together, BSSL and PLRP2 have a synergistic effect, increasing cellular uptake 4-fold compared to the sum of each lipase alone. A synergistic effect was also observed with retinyl ester as a substrate. PLRP2 hydrolyzed cholesteryl ester but not as efficiently as BSSL, and the two had an additive rather than synergistic effect. We conclude the key enzymes in intestinal fat digestion are different in newborns than later in life. Further studies are needed to fully understand this difference and its implication for designing optimal neonatal nutrition.
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| 4. |
- Andersson, Yvonne, et al.
(författare)
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Lactoferrin is responsible for the fungistatic effect of human milk.
- 2000
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Ingår i: Early Human Development. - 0378-3782 .- 1872-6232. ; 59:2, s. 95-105
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Tidskriftsartikel (refereegranskat)abstract
- Human milk has recognized anti-microbial effects and it has been repeatedly shown that breast-fed infants have fewer and less severe infections than formula-fed infants. While most studies have focused on anti-bacterial and anti-viral activities few have focused on the anti-fungal effect of human milk. Dermal and other infections caused by fungi are common in very low birth weight (VLBW) infants. Using a liquid culturing method and Candida albicans and Rhodotorula rubra as representative fungi, we studied the anti-fungal effect of human milk and certain human milk proteins. In vitro, human milk showed potent inhibitory effect on fungal growth. Most, if not all of this effect was caused by lactoferrin via its iron-binding capacity; increasing the iron content of the incubation medium abolished the inhibitory effect. In contrast, other human milk proteins with known or suggested anti-microbial effects rather increased fungal growth. Viability test and electron microscopy revealed that the growth inhibitory effect of human milk, i.e. mediated by lactoferrin, is fungistatic rather than fungicidal.
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| 5. |
- Andersson, Yvonne, et al.
(författare)
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Three variants of parathyroid hormone-related protein messenger RNA are expressed in human mammary gland.
- 1997
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Ingår i: Pediatric Research. - 0031-3998 .- 1530-0447. ; 41:3, s. 380-3
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Tidskriftsartikel (refereegranskat)abstract
- PTH-related protein (PTHrP) is found in a variety of tissues; particularly high levels are present in human milk. The structure of the human PTHrP gene is complex, and alternative splicing allows expression of three different variants PTHrP139, PTHrP173, and PTHrP141, respectively. To determine which of the variants are expressed in human mammary gland a reverse transcriptase polymerase chain reaction (RT-PCR) method was elaborated, distinguishing the three variants. mRNA isolated from human milk cells, human mammary epithelial cells (HMEC) and human nonlactating mammary gland cells were analyzed. The RT-PCR experiments resulted in amplification of DNA fragments corresponding to all three variants for all three cell sources tested. The nucleotide sequences of the PCR fragments were determined and verified to be identical to the reported sequences. Hence, it is concluded that human mammary gland epithelial cells express three variants of PTHrP. Whether these have different physiologic effects in the mammary gland or in the breast fed infant remain to be explored.
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| 6. |
- Johansson, Bente B, et al.
(författare)
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Diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl-ester lipase gene (CEL-MODY) : a protein misfolding disease
- 2011
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Ingår i: Journal of Biological Chemistry. - Bethesda, Md. : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 286:40, s. 34593-34605
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Tidskriftsartikel (refereegranskat)abstract
- CEL-MODY, diabetes with pancreatic lipomatosis and exocrine dysfunction, is due to dominant frame-shift mutations in the acinar cell carboxyl-ester lipase gene (CEL). As Cel knock-out mice do not express the phenotype and the mutant protein has an altered, intrinsically disordered tandem repeat domain, we hypothesized that the disease mechanism might involve a negative effect of the mutant protein. In silico analysis showed that the pI of the tandem repeat was markedly increased from pH 3.3 in wild-type (WT) to 11.8 in mutant (MUT) human CEL. By stably over-expressing CEL-WT and CEL-MUT in HEK293 cells, we found similar glycosylation, ubiquitination, constitutive secretion and quality control of the two proteins. The CEL-MUT protein demonstrated, however, a high propensity to form aggregates found intracellularly and extracellularly. Different physico-chemical properties of the intrinsically disordered tandem repeat domains of WT and MUT proteins may contribute to different short-range and long-range interactions with the globular core domain and other macromolecules, including cell membranes. Thus, we propose that CEL-MODY is a protein misfolding disease caused by a negative gain-of-function effect of the mutant proteins in pancreatic tissues.
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| 7. |
- Li, Xiaonan, et al.
(författare)
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Bile Salt-Stimulated Lipase and Pancreatic Lipase-Related Protein 2 Are the Dominating Lipases in Neonatal Fat Digestion in Mice and Rats.
- 2007
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Ingår i: Pediatr Res. - 0031-3998.
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Tidskriftsartikel (refereegranskat)abstract
- During infancy, the basic conditions for digestion of dietary fat differ from later in life. The bile salt-stimulated lipase (BSSL) is an enzyme expressed in the exocrine pancreas and in some species (including human) also in the lactating mammary gland and secreted with the milk. The aim of this study was to compare the ontogeny of four pancreatic lipases [BSSL, pancreatic triglyceride lipase (PL), pancreatic lipase-related protein 2 (PLRP2), and phospholipase A2 (PLA2)] in one species that supplies BSSL with milk (the mouse) and one that does not (the rat). We followed expression of the four pancreatic lipases from postnatal d 1 until after weaning in both species. We found that BSSL and PLRP2, two lipases with broad substrate specificity, dominated. It was not until weaning that significant expression of PL and PLA2 were induced. Thus, BSSL and PLRP2 seem to be responsible for fat digestion as long as milk is the main food. Moreover, the early temporal pattern of BSSL expression differed between species. We speculate that the milk-borne BSSL is able to compensate for a slower ontogeny of pancreatic BSSL expression in the mouse.PMID: 17805199 [PubMed - as supplied by publisher]
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| 8. |
- Lindquist, Susanne, et al.
(författare)
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A novel target for treatment of inflammatory joint diseases
- 2019
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 78, s. 1525-1526
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The bile salt-stimulated lipase (BSSL) is a hitherto unrecognized player in inflammation. Animals devoid of BSSL (knockout mice) are protected from developing collagen induced arthritis (CIA) and collagen antibody induced arthritis (CAIA), and antibodies directed towards BSSL has been proven to prevent or mitigate arthritis in mouse and rat arthritis models1. In humans, BSSL is present in blood2 and accumulate at sites of inflammation. Patients with acute pancreatitis have significantly increased plasma BSSL levels compared to healthy controls. Whether BSSL in blood originates from pancreas, inflammatory cells, or both remains to be elucidated.Objectives: To determine BSSL concentration in blood samples from patients with inflammatory joint disorders and to evaluate possible relationships between circulating BSSL levels and disease-activity variables.Methods: BSSL concentrations in plasma or serum were determined in patients with rheumatoid arthritis (RA), psoriasis arthritis (PsA), and juvenile idiopathic arthritis (JIA) by a sandwich enzyme-linked immunosorbent assay (ELISA). Correlations between BSSL concentrations and disease activity score, erythrocyte sedimentation rate (ESR), blood levels of C-reactive protein (CRP), S100A8/9, leukocyte- and neutrophil counts, proinflammatory cytokines and chemokines were analyzed using Spearman rank-order correlation.Results: Significant correlations between BSSL concentration in plasma and disease activity score (DAS28, rS=0.31, p=0.007), ESR (rS=0.58, p<0.000), CRP (rS=0.42, p=0.012), leukocytes (rS=0.66, p<0.000), and neutrophils (rS=0.71, p<0.000) were found in RA. The BSSL plasma concentration decreased with duration of treatment with the TNFα inhibitor infliximab, in parallel with decreasing DAS28 score.BSSL concentration was significantly higher in sera from PsA patients with both oligo- and polyarthritis compared with healthy controls. Moreover, BSSL concentration in serum correlated significantly with S100A8/A9 and CRP concentrations (rS=0.54, p<0.001 and rS=0.49, p<0.001, respectively). No correlation between levels of BSSL and cytokines or chemokines were found in RA or PsA plasma or serum, respectively.In JIA, levels of BSSL in serum correlated significantly with JIA disease activity score (JADAS27) (rS=0.26, p=0.007), ESR (rS=0.47, p<0.000), and leukocytes (rS=0.32, p<0.000).Conclusion: BSSL concentration in serum and plasma correlated with disease activity in patients with inflammatory joint disorders, i.e. RA, PsA and JIA. These data in humans support the relevance of our previous studies in rodents and therefore also our hypothesis 1 that BSSL is a novel target for treatment of inflammatory diseases.
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| 9. |
- Lindquist, Susanne, et al.
(författare)
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Bile salt-stimulated lipase plays an unexpected role in arthritis development in rodents
- 2012
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Ingår i: PLOS ONE. - San Fransisco, USA : Public Library Science. - 1932-6203. ; 7:10, s. e47006-
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The present study aimed to explore the hypothesis that bile salt-stimulated lipase (BSSL), in addition to being a key enzyme in dietary fat digestion during early infancy, plays an important role in inflammation, notably arthritis. Methods: Collagen-induced arthritis (CIA) and pristane-induced arthritis (PIA) in rodents are commonly used experimental models that reproduce many of the pathogenic mechanisms of human rheumatoid arthritis, i.e. increased cellular infiltration, synovial hyperplasia, pannus formation, and erosion of cartilage and bone in the distal joints. We used the CIA model to compare the response in BSSL wild type (BSSL-WT) mice with BSSL-deficient 'knock-out' (BSSL-KO) and BSSL-heterozygous (BSSL-HET) littermates. We also investigated if intraperitoneal injection of BSSL-neutralizing antibodies affected the development or severity of CIA and PIA in mice and rats, respectively. Results: In two consecutive studies, we found that BSSL-KO male mice, in contrast to BSSL-WT littermates, were significantly protected from developing arthritis. We also found that BSSL-HET mice were less prone to develop disease compared to BSSL-WT mice, but not as resistant as BSSL-KO mice, suggesting a gene-dose effect. Moreover, we found that BSSL-neutralizing antibody injection reduced both the incidence and severity of CIA and PIA in rodents. Conclusion: Our data strongly support BSSL as a key player in the inflammatory process, at least in rodents. It also suggests the possibility that BSSL-neutralizing agents could serve as a therapeutic model to reduce the inflammatory response in humans.
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| 10. |
- Lindquist, Susanne, et al.
(författare)
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Effects of bile salt-stimulated lipase on blood cells and associations with disease activity in human inflammatory joint disorders
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:8
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Tidskriftsartikel (refereegranskat)abstract
- The bile salt-stimulated lipase (BSSL) was originally recognized as a lipolytic enzyme expressed by the exocrine pancreas and in some species, notably humans, the lactating mammary gland, being secreted into the duodenum and with the mother’s milk, respectively. However, BSSL is also present in the blood and has been assigned additional functions, even beyond the gastrointestinal tract. Conventional BSSL knockout mice are protected from developing disease in animal models of arthritis, and antibodies directed towards BSSL prevent or mitigate disease in similar models. The aim of this study was to investigate the role of BSSL as a newly discovered player in inflammation and specifically in inflammatory joint disorders. As part of mechanism of action, we here show that BSSL is secreted by neutrophils, interacts with monocytes and stimulates their migration in vitro. An anti-BSSL antibody that blocks the human BSSL-monocyte interaction was shown to simultaneously prevent the signaling pathway by which BSSL induce cell migration. Moreover, in this cohort study we show that BSSL levels are significantly higher in blood samples from patients with rheumatoid arthritis and psoriatic arthritis compared to healthy controls. The BSSL levels in patients’ blood also correlated with disease activity scores and established inflammatory markers. Hence, although the mode of action is not yet fully clarified, we conclude that BSSL could be considered a proinflammatory component in the innate immune system and thus a possible novel target for treatment of chronic inflammation.
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