| 1. |
- Hochberg, Z., et al.
(författare)
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Child health, developmental plasticity, and epigenetic programming
- 2011
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Ingår i: Endocrine reviews. - : The Endocrine Society. - 0163-769X .- 1945-7189. ; 32:2, s. 159-224
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Forskningsöversikt (refereegranskat)abstract
- Plasticity in developmental programming has evolved in order to provide the best chances of survival and reproductive success to the organism under changing environments. Environmental conditions that are experienced in early life can profoundly influence human biology and long-term health. Developmental origins of health and disease and life-history transitions are purported to use placental, nutritional, and endocrine cues for setting long-term biological, mental, and behavioral strategies in response to local ecological and/or social conditions. The window of developmental plasticity extends from preconception to early childhood and involves epigenetic responses to environmental changes, which exert their effects during life-history phase transitions. These epigenetic responses influence development, cell- and tissue-specific gene expression, and sexual dimorphism, and, in exceptional cases, could be transmitted transgenerationally. Translational epigenetic research in child health is a reiterative process that ranges from research in the basic sciences, preclinical research, and pediatric clinical research. Identifying the epigenetic consequences of fetal programming creates potential applications in clinical practice: the development of epigenetic biomarkers for early diagnosis of disease, the ability to identify susceptible individuals at risk for adult diseases, and the development of novel preventive and curative measures that are based on diet and/or novel epigenetic drugs.
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| 2. |
- van de Ven, Johannes P. H., et al.
(författare)
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A functional variant in the CFI gene confers a high risk of age-related macular degeneration
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:7, s. 813-813
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Tidskriftsartikel (refereegranskat)abstract
- Up to half of the heritability of age-related macular degeneration (AMD) is explained by common variants(1-5). Here, we report the identification of a rare, highly penetrant missense mutation in CFI encoding a p.Gly119Arg substitution that confers high risk of AMD (P = 3.79 x 10(-6); odds ratio (OR) = 22.20, 95% confidence interval (CI) = 2.98-164.49). Plasma and sera from cases carrying the p.Gly119Arg substitution mediated the degradation of C3b, both in the fluid phase and on the cell surface, to a lesser extent than those from controls. Recombinant protein studies showed that the Gly119Arg mutant protein is both expressed and secreted at lower levels than wild-type protein. Consistent with these findings, human CFI mRNA encoding Arg119 had reduced activity compared to wild-type mRNA encoding Gly119 in regulating vessel thickness and branching in the zebrafish retina. Taken together, these findings demonstrate that rare, highly penetrant mutations contribute to the genetic burden of AMD.
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| 3. |
- Bueter, Marco, et al.
(författare)
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Gastric bypass increases energy expenditure in rats.
- 2010
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Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 138:5, s. 1845-53
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Mechanisms underlying weight loss maintenance after gastric bypass are poorly understood. Our aim was to examine the effects of gastric bypass on energy expenditure in rats. METHODS: Thirty diet-induced obese male Wistar rats underwent either gastric bypass (n = 14), sham-operation ad libitum fed (n = 8), or sham-operation body weight-matched (n = 8). Energy expenditure was measured in an open circuit calorimetry system. RESULTS: Twenty-four-hour energy expenditure was increased after gastric bypass (4.50 +/- 0.04 kcal/kg/h) compared with sham-operated, ad libitum fed (4.29 +/- 0.08 kcal/kg/h) and sham-operated, body weight-matched controls (3.98 +/- 0.10 kcal/kg/h, P < .001). Gastric bypass rats showed higher energy expenditure during the light phase than sham-operated control groups (sham-operated, ad libitum fed: 3.63 +/- 0.04 kcal/kg/h vs sham-operated, body weight-matched: 3.42 +/- 0.05 kcal/kg/h vs bypass: 4.12 +/- 0.03 kcal/kg/h, P < .001). Diet-induced thermogenesis was elevated after gastric bypass compared with sham-operated, body weight-matched controls 3 hours after a test meal (0.41% +/- 1.9% vs 10.5% +/- 2.0%, respectively, P < .05). The small bowel of gastric bypass rats was 72.1% heavier because of hypertrophy compared with sham-operated, ad libitum fed rats (P < .0001). CONCLUSIONS: Gastric bypass in rats prevented the decrease in energy expenditure after weight loss. Diet-induced thermogenesis was higher after gastric bypass compared with body weight-matched controls. Raised energy expenditure may be a mechanism explaining the physiologic basis of weight loss after gastric bypass.
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| 4. |
- Bueter, Marco, et al.
(författare)
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Vagal sparing surgical technique but not stoma size affects body weight loss in rodent model of gastric bypass.
- 2010
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Ingår i: Obesity surgery. - : Springer Science and Business Media LLC. - 1708-0428 .- 0960-8923. ; 20:5, s. 616-22
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to evaluate whether gastric bypass with or without vagal preservation resulted in a different outcome. METHODS: Body weight, food intake and postprandial peptide YY (PYY) and glucagon-like peptide (GLP-1) levels were compared between gastric bypass (n = 55) and sham-operated rats (n = 27) in three groups. In group 1 (n = 17), the vagal nerve was not preserved, while in group 2 the vagal nerve was preserved during gastric bypass (n = 10). In group 3, gastric bypass rats (n = 28) were randomised for either one of the two techniques. RESULTS: Rats in which the vagal nerve was preserved during gastric bypass showed a lower body weight (p < 0.001) and reduced food intake (p < 0.001) compared to rats in which the vagal nerve was not preserved during the gastric bypass operation. Levels of PYY and GLP-1 were significantly increased after gastric bypass compared to sham-operated controls (p < 0.05), but there was no difference between gastric bypass rats with and without vagal preservation. Differences in food intake and body weight were not related to the size of the gastro-jejunostomy in gastric bypass rats. There were no signs of malabsorption or inflammation after gastric bypass. CONCLUSION: We propose that the vagal nerve should be preserved during the gastric bypass operation as this might play an important role for the mechanisms that induce weight loss and reduce food intake in rats. In contrast, the gastro-jejunal stoma size was found to be of minor relevance.
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| 5. |
- Cohen, R., et al.
(författare)
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Role of proximal gut exclusion from food on glucose homeostasis in patients with Type 2 diabetes
- 2013
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 30, s. 1482-1486
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To report Type 2 diabetes-related outcomes after the implantation of a duodenal-jejunal bypass liner device and to investigate the role of proximal gut exclusion from food in glucose homeostasis using the model of this device. Methods: Sixteen patients with Type 2 diabetes and BMI <36kg/m2 were evaluated before and 1, 12 and 52weeks after duodenal-jejunal bypass liner implantation and 26weeks after explantation. Mixed-meal tolerance tests were conducted over a period of 120min and glucose, insulin and C-peptide levels were measured. The Matsuda index and the homeostatic model of assessment of insulin resistance were used for the estimation of insulin sensitivity and insulin resistance. The insulin secretion rate was calculated using deconvolution of C-peptide levels. Results: Body weight decreased by 1.3kg after 1week and by 2.4kg after 52weeks (P<0.001). One year after duodenal-jejunal bypass liner implantation, the mean (sem) HbA1c level decreased from 71.3 (2.4) mmol/mol (8.6[0.2]%) to 58.1 (4.4) mmol/mol (7.5 [0.4]%) and mean (sem) fasting glucose levels decreased from 203.3 (13.5) mg/dl to 155.1 (13.1) mg/dl (both P<0.001). Insulin sensitivity improved by >50% as early as 1week after implantation as measured by the Matsuda index and the homeostatic model of assessment of insulin resistance (P<0.001), but there was a trend towards deterioration in all the above-mentioned variables 26weeks after explantation. Fasting insulin levels, insulin area under the curve, fasting C-peptide, C-peptide area under the curve, fasting insulin and total insulin secretion rates did not change during the duodenal-jejunal bypass liner implantation period or after explantation. Conclusions: The duodenal-jejunal bypass liner improves glycaemia in overweight and obese patients with Type 2 diabetes by rapidly improving insulin sensitivity. A reduction in hepatic glucose output is the most likely explanation for this improvement. Diabetic Medicine © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.
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| 6. |
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| 7. |
- Smailhodzic, Dzenita, et al.
(författare)
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Zinc supplementation inhibits complement activation in age-related macular degeneration.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. AMD is a multifactorial disorder but complement-mediated inflammation at the level of the retina plays a pivotal role. Oral zinc supplementation can reduce the progression of AMD but the precise mechanism of this protective effect is as yet unclear. We investigated whether zinc supplementation directly affects the degree of complement activation in AMD and whether there is a relation between serum complement catabolism during zinc administration and the complement factor H (CFH) gene or the Age-Related Maculopathy susceptibility 2 (ARMS2) genotype. In this open-label clinical study, 72 randomly selected AMD patients in various stages of AMD received a daily supplement of 50 mg zinc sulphate and 1 mg cupric sulphate for three months. Serum complement catabolism-defined as the C3d/C3 ratio-was measured at baseline, throughout the three months of supplementation and after discontinuation of zinc administration. Additionally, downstream inhibition of complement catabolism was evaluated by measurement of anaphylatoxin C5a. Furthermore, we investigated the effect of zinc on complement activation in vitro. AMD patients with high levels of complement catabolism at baseline exhibited a steeper decline in serum complement activation (p<0.001) during the three month zinc supplementation period compared to patients with low complement levels. There was no significant association of change in complement catabolism and CFH and ARMS2 genotype. In vitro zinc sulphate directly inhibits complement catabolism in hemolytic assays and membrane attack complex (MAC) deposition on RPE cells. This study provides evidence that daily administration of 50 mg zinc sulphate can inhibit complement catabolism in AMD patients with increased complement activation. This could explain part of the mechanism by which zinc slows AMD progression.
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| 8. |
- Sonnenschein-van der Voort, Agnes M. M, et al.
(författare)
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Preterm birth, infant weight gain, and childhood asthma risk: A meta-analysis of 147,000 European children
- 2014
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 133:5, s. 1317-1329
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. Objectives: We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). Methods: First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age less than 37 weeks) and low birth weight (less than 2500 g) with childhood asthma outcomes. Results: Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P less than. 05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27). Conclusion: Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.
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| 9. |
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| 10. |
- Verzijden, Machteld, et al.
(författare)
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The impact of learning on sexual selection and speciation.
- 2012
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Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 1872-8383 .- 0169-5347. ; 27:9, s. 511-519
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Tidskriftsartikel (refereegranskat)abstract
- Learning is widespread in nature, occurring in most animal taxa and in several different ecological contexts and, thus, might play a key role in evolutionary processes. Here, we review the accumulating empirical evidence for the involvement of learning in mate choice and the consequences for sexual selection and reproductive isolation. We distinguish two broad categories: learned mate preferences and learned traits under mate selection (such as bird song). We point out that the context of learning, namely how and when learning takes place, often makes a crucial difference to the predicted evolutionary outcome. Factors causing biases in learning and when one should expect the evolution of learning itself are also explored.
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| 11. |
- Vincent, Royce P, et al.
(författare)
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Higher circulating bile acid concentrations in obese patients with type 2 diabetes.
- 2013
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Ingår i: Annals of clinical biochemistry. - : SAGE Publications. - 1758-1001. ; 50:Pt 4, s. 360-4
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Tidskriftsartikel (refereegranskat)abstract
- Bile acids (BAs) play an important role in releasing incretin hormones via the enteroendocrine L-cell surface TGR5 receptors. The aim of this study was to investigate the difference in BA concentration at baseline and in response to a meal stimulus between type 2 diabetes mellitus (T2DM) and a matched normoglycaemic group.
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| 12. |
- Werling, Malin, 1967, et al.
(författare)
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Enhanced fasting and post-prandial plasma bile acid responses after Roux-en-Y gastric bypass surgery.
- 2013
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:11, s. 1257-1264
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Exogenous bile acid (BA) administration is associated with beneficial metabolic effects very similar to those seen after Roux-en-Y gastric bypass (RYGB) surgery. Re-routing of bile into a biliopancreatic limb with simultaneous exclusion of food occurs after RYGB, with subsequent increased fasting plasma BAs. The study assessed fasting and post-prandial plasma BA response before and 15 months after RYGB. Material and methods. The prospective study recruited 63 obese individuals (43 females), aged 43 (36-56) [median (IQR)] years. Blood samples were collected before and every 30 min for 120 min after a standard 400 kcal meal. Fasting and post-prandial plasma BAs, glucagons like peptide-1 (GLP-1), -tyrosine (PYY), fasting C-reactive protein (CRP), glucose and insulin were measured and homeostasis model assessment-insulin resistance (HOMA-IR) was calculated. Results. Following RYGB, body mass index, CRP, fasting glucose and HOMA-IR decreased; 43.7 (39.3-49.2) kg/m(2) to 29.2 (25.1-35.0) kg/m(2), 7.9 (4.1-11.9) mg/L to 0.4 (0.2-1.0) mg/L, 5.5 (5.0-6.0) mmol/L to 4.6 (4.3-4.9) mmol/L and 5.9 (3.5-9.2) to 1.7 (1.1-2.2), respectively, all P < 0.001. Fasting total BAs, GLP-1 and PYY increased after RYGB; 1.69 (0.70-2.56) µmol/L to 2.43 (1.23-3.82) µmol/L (P = 0.02), 6.8 (1.5-15.3) pmol/L to 17.1 (12.6-23.9) pmol/L (P < 0.001) and 4.0 (1.0-7.1) pmol/L to 15.2 (10.0-28.3) pmol/L (P < 0.001), respectively. The area under the curve for post-prandial total BAs, total glycine-conjugated BAs, GLP-1 and PYY were greater after RYGB; 486 (312-732) µmol/L/min versus 1012 (684-1921) µmol/L/min, 315 (221-466) µmol/L/min versus 686 (424-877) µmol/L/min, 3679 (3162-4537) pmol/L/min versus 5347 (4727-5781) pmol/L/min and 1887 (1423-2092) pmol/L/min versus 3296 (2534-3834) pmol/L/min, respectively, all P < 0.0001. Conclusion. Weight loss following RYGB is associated with an increase in post-prandial plasma BA response due to larger amounts of glycine-conjugated BAs. This suggests up regulation of BA production and conjugation after RYGB.
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