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| 124. |
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| 125. |
- 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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| 126. |
- Johansson, Ulrica, 1974-, et al.
(författare)
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A randomized, controlled trial of a Nordic, protein-reduced complementary diet: effects on dietary intake, biomarkers and growth until 18 months of age
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Plant-based foods introduced during complementary feeding (CF) can contribute to long-term health andclimate friendly diet, but longitudinal multicomponent approaches are lacking.Objectives: To investigate the effects of a protein-reduced, Nordic complementary diet on dietary intake, biomarkers andgrowth and compared to the current Swedish dietary recommendations for infants until 18 mo of age.Design: Healthy, term infants (n=250) were recruited and randomly allocated to either a Nordic diet group (NG) or aconventional diet group (CG). From 4-6 mo of age, the NG followed a taste portions schedule with Nordic fruitand vegetables. From 6 mo up to 18 mo of age, the NG was supplied with Nordic homemade baby food recipes,protein-reduced baby food products and parental support. The CG followed the current Swedish dietaryrecommendations for infants. Dietary intake data, biomarkers and anthropometry were collected frombaseline up to 18 mo of age.Results: Of the 250 infants, 82% (n=206) completed the study. The NG consumed daily 42-45% more fruit andvegetables compared to the CG at 12 and 18 mo of age (p<0.001). Plasma folate was higher in the NGcompared to the CG at 12 mo (p<0.001) and 18 mo of age (p=0.003) and protein intake and blood ureanitrogen (BUN) were lower at both 12 and 18 mo of age (p<0.001). There were no group differences in energyintake (EI), growth, iron status or other biomarkers.Conclusions: The NG consumed significantly more plant-based Nordic foods compared to CG, a difference that lasted at leastuntil 18 mo of age. The lower protein intake in the NG had no effect on growth or iron status. The introductionof a protein-reduced, Nordic diet during CF is safe and feasible, and benefits a sustainable environment andhealth already during infancy and early childhood.
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| 128. |
- Karlsson Videhult, Frida, 1980-
(författare)
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Effects of early probiotic supplementation in a pediatric setting : Focus on body composition, metabolism and inflammation
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- We aimed to determine the short- and long-term effects on growth, body composition, metabolic and inflammatory markers following supplementation with the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) during weaning. Methods: One-hundred and seventy-nine healthy, infants in Umeå city, Västerbotten County were randomised to daily intake of cereals with (n=89) or without (n=90) LF19 108 colony-forming units from 4 to 13 months of age. Weight, length, head circumference and body composition, assessed by skinfold thickness, were examined at 4, 5.5, 6.5, 9, 12 and 13 months of age. Venous blood was drawn at 5.5 and 13 months. In all, 171 infants completed the intervention and were invited to a follow-up at 8-9 years of age between 2009 and 2011, 120 children participated. Weight, height, sagittal abdominal diameter and body composition (using Dual Energy X-ray Absorptiometry-scan) were measured. Data on weight and height at 4 years were collected from medical records. The families filled out a 4-day food record and a food frequency questionnaire, physical activity was assessed using a pedometer for 7 days. At 5.5, 13 months and 8-9 years of age we analysed the serum blood lipid profile. At 8-9 years fasting glucose, insulin, aspartate and alanine transaminases were analysed in serum. Homeostatic Model Assessment index was calculated. At follow-up serum adiponectin, high-sensitivity C-reactive protein and plasma C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide 1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin were analysed. For characterisation of the plasma metabolome, a subgroup (n=40) was analysed at 5.5 and 13 months of age by gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) analysis and in all (n=112) children at the follow-up using untargeted GC-GC/MS. Results: There were no differences between the LF19 and placebo group regarding body weight, length/height at any assessment from 4 months to 8-9 years of age; nor were there any differences between the groups in body composition. In the LF19 group 19 % were overweight/obese, the corresponding number was 21 % in the placebo group (p=0.78). Analysed metabolic and inflammatory markers, both during the intervention and the follow-up did not differ between the two groups. At 13 months of age lower levels of palmitic acid and palmitoleic acid (both p<0.04) and higher levels of putrescine (p<0.01) were seen in the LF19 compared to the placebo group. These differences did not persist at 8-9 years of age. At that age, we found statistically stronger models when comparing overweight/obese and normal weight children as well as in relation to sex. Conclusion: Early intervention with the probiotic LF19 at the time of weaning exerted transient effects on the metabolome. In a long-term perspective, we found neither benefit nor harm on growth, body composition, metabolic or inflammatory markers following supplementation with LF19 during weaning.
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| 129. |
- Karlsson Videhult, Frida, et al.
(författare)
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Impact of probiotics during weaning on the metabolic and inflammatory profile : follow-up at school age
- 2015
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Ingår i: International Journal of Food Sciences and Nutrition. - : Taylor & Francis Group. - 0963-7486 .- 1465-3478. ; 66:6, s. 686-691
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesised that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) (dep. nr LMG P-17806) during weaning would program the metabolic and inflammatory profile and studied its association with previously assessed body composition. In a double-blind, placebo-controlled trial, 179 infants were randomised to daily feeding of cereals with or without LF19 10 8 CFU from 4 to 13 months of age. At age 8-9 years, 120 children were reassessed. Using high-sensitivity multiplex immunoassay technology and ELISA, we found that overweight/obese children had increased plasma C-peptide, plasminogen activator inhibitor-1, leptin and serum high-sensitivity C-reactive protein (hsCRP) after overnight fasting compared with normal weight children, independently of LF19. After excluding the obese, leptin and hsCRP were still increased, revealing an aberrant metabolic and inflammatory state already in overweight, pre-pubertal children. Higher body mass index z-score, sagittal abdominal diameter, truncal and total body fat % were associated with an aberrant metabolic and inflammatory profile, emphasising the need for early prevention strategies although no programming effect of LF19 was observed.
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| 130. |
- Karlsson Videhult, Frida, et al.
(författare)
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Probiotics during weaning : a follow-up study on effects on body composition and metabolic markers at school age
- 2015
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 54:3, s. 355-363
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: An aberrant gut microbiome has been suggested to contribute to the worldwide epidemic of obesity. In animal models, the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) induced upregulation of genes involved in energy homoeostasis, reduced body fat and altered the serum (S) lipoprotein profile. In our previous report, feeding LF19 to infants during weaning impacted the global plasma metabolome. LF19 lowered palmitoleic acid, a monounsaturated fatty acid associated with hypertriglyceridemia and increased visceral adiposity. Therefore, we assessed if feeding LF19 from 4 to 13 months of age would have long-term effects on body composition, growth and metabolic markers.METHODS: Of 179 children included in our baseline study, 120 entered the follow-up at 8-9 years of age, n = 58 in the probiotic and n = 62 in the placebo group. Body composition was measured using dual energy X-ray absorptiometry. Anthropometrics of the child and accompanying parent(s) were assessed. S-lipids, insulin, glucose and transaminases were determined after overnight fasting.RESULTS: LF19 did not affect body mass index z-score, sagittal abdominal diameter, fat-free mass, fat mass index, truncal fat %, android or gynoid fat % and had no long-term impact on any of the assessed metabolic markers (p > 0.05).CONCLUSION: Feeding LF19 during infancy did not modulate body composition, growth or any of the assessed metabolic markers at school age. The steady increase in probiotic products targeting infants and children calls for long-term follow-up of initiated probiotic intervention studies.
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