| 21. |
- Green, Charlotte J., et al.
(författare)
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Studying non-alcoholic fatty liver disease : the ins and outs of in vivo, ex vivo and in vitro human models
- 2020
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Ingår i: Hormone Molecular Biology and Clinical Investigation. - : Walter de Gruyter GmbH. - 1868-1883 .- 1868-1891. ; 41:1
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Forskningsöversikt (refereegranskat)abstract
- The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. Determining the pathogenesis and pathophysiology of human NAFLD will allow for evidence-based prevention strategies, and more targeted mechanistic investigations. Various in vivo, ex situ and in vitro models may be utilised to study NAFLD; but all come with their own specific caveats. Here, we review the human-based models and discuss their advantages and limitations in regards to studying the development and progression of NAFLD. Overall, in vivo whole-body human studies are advantageous in that they allow for investigation within the physiological setting, however, limited accessibility to the liver makes direct investigations challenging. Non-invasive imaging techniques are able to somewhat overcome this challenge, whilst the use of stable-isotope tracers enables mechanistic insight to be obtained. Recent technological advances (i.e. normothermic machine perfusion) have opened new opportunities to investigate whole-organ metabolism, thus ex situ livers can be investigated directly. Therefore, investigations that cannot be performed in vivo in humans have the potential to be undertaken. In vitro models offer the ability to perform investigations at a cellular level, aiding in elucidating the molecular mechanisms of NAFLD. However, a number of current models do not closely resemble the human condition and work is ongoing to optimise culturing parameters in order to recapitulate this. In summary, no single model currently provides insight into the development, pathophysiology and progression across the NAFLD spectrum, each experimental model has limitations, which need to be taken into consideration to ensure appropriate conclusions and extrapolation of findings are made.
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| 22. |
- Gürdeniz, Gözde, et al.
(författare)
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Analysis of the SYSDIET Healthy Nordic Diet randomized trial based on metabolic profiling reveal beneficial effects on glucose metabolism and blood lipids
- 2021
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 41:2, s. 441-451
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Intake assessment in multicenter trials is challenging, yet important for accurate outcome evaluation. The present study aimed to characterize a multicenter randomized controlled trial with a healthy Nordic diet (HND) compared to a Control diet (CD) by plasma and urine metabolic profiles and to associate them with cardiometabolic markers.METHODS: During 18-24 weeks of intervention, 200 participants with metabolic syndrome were advised at six centres to eat either HND (e.g. whole-grain products, berries, rapeseed oil, fish and low-fat dairy) or CD while being weight stable. Of these 166/159 completers delivered blood/urine samples. Metabolic profiles of fasting plasma and 24 h pooled urine were analysed to identify characteristic diet-related patterns. Principal components analysis (PCA) scores (i.e. PC1 and PC2 scores) were used to test their combined effect on blood glucose response (primary endpoint), serum lipoproteins, triglycerides, and inflammatory markers.RESULTS: The profiles distinguished HND and CD with AUC of 0.96 ± 0.03 and 0.93 ± 0.02 for plasma and urine, respectively, with limited heterogeneity between centers, reflecting markers of key foods. Markers of fish, whole grain and polyunsaturated lipids characterized HND, while CD was reflected by lipids containing palmitoleic acid. The PC1 scores of plasma metabolites characterizing the intervention is associated with HDL (β = 0.05; 95% CI: 0.02, 0.08; P = 0.001) and triglycerides (β = -0.06; 95% CI: -0.09, -0.03; P < 0.001). PC2 scores were related with glucose metabolism (2 h Glucose, β = 0.1; 95% CI: 0.05, 0.15; P < 0.001), LDL (β = 0.06; 95% CI: 0.01, 0.1; P = 0.02) and triglycerides (β = 0.11; 95% CI: 0.06, 0.15; P < 0.001). For urine, the scores were related with LDL cholesterol.CONCLUSIONS: Plasma and urine metabolite profiles from SYSDIET reflected good compliance with dietary recommendations across the region. The scores of metabolites characterizing the diets associated with outcomes related with cardio-metabolic risk. Our analysis therefore offers a novel way to approach a per protocol analysis with a balanced compliance assessment in larger multicentre dietary trials. The study was registered at clinicaltrials.gov with NCT00992641.
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| 23. |
- Hjort, Anna, 1988, et al.
(författare)
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Glycemic variability assessed using continuous glucose monitoring in individuals without diabetes and associations with cardiometabolic risk markers: A systematic review and meta-analysis
- 2024
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Ingår i: Clinical Nutrition. - 1532-1983 .- 0261-5614. ; 43:4, s. 915-925
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Continuous glucose monitoring (CGM) provides data on short-term glycemic variability (GV). GV is associated with adverse outcomes in individuals with diabetes. Whether GV is associated with cardiometabolic risk in individuals without diabetes is unclear. We systematically reviewed the literature to assess whether GV is associated with cardiometabolic risk markers or outcomes in individuals without diabetes. Methods: Searches were performed in PubMed/Medline, Embase and Cochrane from inception through April 2022. Two researchers were involved in study selection, data extraction and quality assessment. Studies evaluating GV using CGM for ≥24 h were included. Studies in populations with acute and/or critical illness were excluded. Both narrative synthesis and meta-analyzes were performed, depending on outcome. Results: Seventy-one studies were included; the majority were cross-sectional. Multiple measures of GV are higher in individuals with compared to without prediabetes and GV appears to be inversely associated with beta cell function. In contrast, GV is not clearly associated with insulin sensitivity, fatty liver disease, adiposity, blood lipids, blood pressure or oxidative stress. However, GV may be positively associated with the degree of atherosclerosis and cardiovascular events in individuals with coronary disease. Conclusion: GV is elevated in prediabetes, potentially related to beta cell dysfunction, but less clearly associated with obesity or traditional risk factors. GV is associated with coronary atherosclerosis development and may predict cardiovascular events and type 2 diabetes. Prospective studies are warranted, investigating the predictive power of GV in relation to incident disease. GV may be an important risk measure also in individuals without diabetes.
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| 24. |
- Hodson, Leanne, et al.
(författare)
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The influence of dietary fatty acids on liver fat content and metabolism
- 2020
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Ingår i: Proceedings of the Nutrition Society. - : CAMBRIDGE UNIV PRESS. - 0029-6651 .- 1475-2719. ; 79:1, s. 30-41
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Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic fatty liver disease encompasses a spectrum of conditions from hepatic steatosis through to cirrhosis; obesity is a known risk factor. The liver plays a major role in regulating fatty acid metabolism and perturbations in intrahepatic processes have potential to impact on metabolic health. It remains unclear why intra-hepatocellular fat starts to accumulate, but it likely involves an imbalance between fatty acid delivery to the liver, fatty acid synthesis and oxidation within the liver and TAG export from the liver. As man spends the majority of the day in a postprandial rather than postabsorptive state, dietary fatty acid intake should be taken into consideration when investigating why intra-hepatic fat starts to accumulate. This review will discuss the impact of the quantity and quality of dietary fatty acids on liver fat accumulation and metabolism, along with some of the potential mechanisms involved. Studies investigating the role of dietary fat in liver fat accumulation, although surprisingly limited, have clearly demonstrated that it is total energy intake, rather than fat intake per se, that is a key mediator of liver fat content; hyperenergetic diets increase liver fat whilst hypoenergetic diets decrease liver fat content irrespective of total fat content. Moreover, there is now, albeit limited evidence emerging to suggest the composition of dietary fat may also play a role in liver fat accumulation, with diets enriched in saturated fat appearing to increase liver fat content to a greater extent when compared with diets enriched in unsaturated fats.
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| 25. |
- Hodson, Leanne, et al.
(författare)
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Using total plasma triacylglycerol to assess hepatic de novo lipogenesis as an alternative to VLDL triacylglycerol
- 2020
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 125:3, s. 211-216
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hepatic de novo lipogenesis (DNL) is ideally measured in very low-density lipoprotein (VLDL)-triacylglycerol (TAG). In the fasting state, the majority of plasma TAG typically represents VLDL-TAG; however, the merits of measuring DNL in total plasma TAG have not been assessed. This study aimed to assess the performance of DNL measured in VLDL-TAG (DNLVLDL-TAG) compared to that measured in total plasma TAG (DNLPlasma-TAG).Methods: Using deuterated water, newly synthesised palmitate was determined in fasting plasma VLDL-TAG and total TAG in 63 subjects taking part in multiple studies resulting in n = 123 assessments of DNL (%new palmitate of total palmitate). Subjects were split into tertiles to investigate if DNLPlasma-TAG could correctly classify subjects having ‘high’ (top tertile) and ‘low’ (bottom tertile) DNL. Repeatability was assessed in a subgroup (n = 16) with repeat visits.Results: DNLVLDL-TAG was 6.8% (IQR 3.6–10.7%) and DNLPlasma-TAG was 7.5% (IQR 4.0%−11.0%), and the correlation between the methods was rs = 0.62 (p < 0.0001). Bland–Altman plots demonstrated similar performance (mean difference 0.81%, p = 0.09); however, the agreement interval was wide (−9.6% to 11.2%). Compared to DNLVLDL-TAG, 54% of subjects with low DNL were correctly classified, whilst 66% of subjects with high DNL were correctly classified using DNLPlasma-TAG. Repeatability was acceptable (i.e. not different) at the group level, but the majority of subjects had an intra-individual variability over 25%.Conclusion: DNL in total plasma TAG performed similarly to DNL in VLDL-TAG at the group level, but there was large variability at the individual level. We suggest that plasma TAG could be useful for comparing DNL between groups.
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| 26. |
- Iggman, David, et al.
(författare)
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Role of dietary fats in modulating cardiometabolic risk during moderate weight gain : a randomized double-blind overfeeding trial (LIPOGAIN study)
- 2014
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Ingår i: Journal of the American Heart Association. - 2047-9980 .- 2047-9980. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study.METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001).CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA.CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.
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| 27. |
- Johansson, Hans-Erik, 1960-, et al.
(författare)
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Energy restriction in obese women suggest linear reduction of hepatic fat content and time-dependent metabolic improvements
- 2019
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Ingår i: Nutrition & Diabetes. - : Springer Science and Business Media LLC. - 2044-4052 .- 2044-4052. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Energy restriction reduces liver fat, improves hepatic insulin resistance and lipid metabolism. However, temporal data in which these metabolic improvements occur and their interplay is incomplete. By performing repeated MRI scans and blood analysis at day 0, 3, 7, 14 and 28 the temporal changes in liver fat and related metabolic factors were assessed at five times during a low-calorie diet (LCD, 800-1100 kcal/day) in ten obese non-diabetic women (BMI 41.7 ± 2.6 kg/m2) whereof 6 had NAFLD. Mean weight loss was 7.4 ± 1.2 kg (0.7 kg/day) and liver fat decreased by 51 ± 16%, resulting in only three subjects having NAFLD at day 28. Marked alteration of insulin, NEFA, ALT and 3-hydroxybuturate was evident 3 days after commencing LCD, whereas liver fat showed a moderate but a linear reduction across the 28 days. Other circulating-liver fat markers (e.g. triglycerides, adiponectin, stearoyl-CoA desaturase-1 index, fibroblast growth factor 21) demonstrated modest and variable changes. Marked elevations of NEFA, 3-hydroxybuturate and ALT concentrations occurred until day 14, likely reflecting increased tissue lipolysis, fat oxidation and upregulated hepatic fatty acid oxidation. In summary, these results suggest linear reduction in liver fat, time-specific changes in metabolic markers and insulin resistance in response to energy restriction.
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| 28. |
- Kolehmainen, Marjukka, et al.
(författare)
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Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome.
- 2015
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 101:1, s. 228-239
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previously, a healthy Nordic diet (ND) has been shown to have beneficial health effects close to those of Mediterranean diets.OBJECTIVE: The objective was to explore whether the ND has an impact on gene expression in abdominal subcutaneous adipose tissue (SAT) and whether changes in gene expression are associated with clinical and biochemical effects.DESIGN: Obese adults with features of the metabolic syndrome underwent an 18- to 24-wk randomized intervention study comparing the ND with the control diet (CD) (the SYSDIET study, carried out within Nordic Centre of Excellence of the Systems Biology in Controlled Dietary Interventions and Cohort Studies). The present study included participants from 3 Nordic SYSDIET centers [Kuopio (n = 20), Lund (n = 18), and Oulu (n = 18)] with a maximum weight change of ±4 kg, highly sensitive C-reactive protein concentration <10 mg/L at the beginning and the end of the intervention, and baseline body mass index (in kg/m(2)) <38. SAT biopsy specimens were obtained before and after the intervention and subjected to global transcriptome analysis with Gene 1.1 ST Arrays (Affymetrix).RESULTS: Altogether, 128 genes were differentially expressed in SAT between the ND and CD (nominal P < 0.01; false discovery rate, 25%). These genes were overrepresented in pathways related to immune response (adjusted P = 0.0076), resulting mainly from slightly decreased expression in the ND and increased expression in the CD. Immune-related pathways included leukocyte trafficking and macrophage recruitment (e.g., interferon regulatory factor 1, CD97), adaptive immune response (interleukin32, interleukin 6 receptor), and reactive oxygen species (neutrophil cytosolic factor 1). Interestingly, the regulatory region of the 128 genes was overrepresented for binding sites for the nuclear transcription factor κB.CONCLUSION: A healthy Nordic diet reduces inflammatory gene expression in SAT compared with a control diet independently of body weight change in individuals with features of the metabolic syndrome. The study was registered at clinicaltrials.gov as NCT00992641.
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| 29. |
- Lagergren, Fredrik, et al.
(författare)
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Kilometre-scale simulations over Fennoscandia reveal a large loss of tundra due to climate warming
- 2024
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Ingår i: Biogeosciences. - 1726-4170 .- 1726-4189. ; 21:5, s. 1093-1116
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Tidskriftsartikel (refereegranskat)abstract
- The Fennoscandian boreal and mountain regions harbour a wide range of vegetation types, from boreal forest to high alpine tundra and barren soils. The area is facing a rise in air temperature above the global average and changes in temperature and precipitation patterns. This is expected to alter the Fennoscandian vegetation composition and change the conditions for areal land use such as forestry, tourism and reindeer husbandry. In this study we used a unique high-resolution (3 km) climate scenario with considerable warming resulting from strongly increasing carbon dioxide emissions to investigate how climate change can alter the vegetation composition, biodiversity and availability of suitable reindeer forage. Using a dynamical vegetation model, including a new implementation of potential reindeer grazing, resulted in simulated vegetation maps of unprecedented high resolution for such a long time period and spatial extent. The results were evaluated at the local scale using vegetation inventories and for the whole area against satellite-based vegetation maps. A deeper analysis of vegetation shifts related to statistics of threatened species was performed in six “hotspot” areas containing records of rare and threatened species. In this high-emission scenario, the simulations show dramatic shifts in the vegetation composition, accelerating at the end of the century. Alarmingly, the results suggest the southern mountain alpine region in Sweden will be completely covered by forests at the end of the 21st century, making preservation of many rare and threatened species impossible. In the northern alpine regions, most vegetation types will persist but shift to higher elevations with reduced areal extent, endangering vulnerable species. Simulated potential for reindeer grazing indicates latitudinal differences, with higher potential in the south in the current climate. In the future these differences will diminish, as the potentials will increase in the north, especially for the summer grazing grounds. These combined results suggest significant shifts in vegetation composition over the present century for this scenario, with large implications for nature conservation, reindeer husbandry and forestry.
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| 30. |
- Lankinen, Maria, et al.
(författare)
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A Healthy Nordic Diet Alters the Plasma Lipidomic Profile in Adults with Features of Metabolic Syndrome in a Multicenter Randomized Dietary Intervention
- 2016
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Ingår i: Journal of Nutrition. - New York, USA : Oxford University Press. - 0022-3166 .- 1541-6100. ; 146:4, s. 662-672
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A healthy Nordic diet is associated with improvements in cardiometabolic risk factors, but the effect on lipidomic profile is not known.OBJECTIVE: The aim was to investigate how a healthy Nordic diet affects the fasting plasma lipidomic profile in subjects with metabolic syndrome.METHODS: Men and women (n = 200) with features of metabolic syndrome [mean age: 55 y; body mass index (in kg/m(2)): 31.6] were randomly assigned to either a healthy Nordic (n = 104) or a control (n = 96) diet for 18 or 24 wk at 6 centers. Of the participants, 156 completed the study with plasma lipidomic measurements. The healthy Nordic diet consisted of whole grains, fruits, vegetables, berries, vegetable oils and margarines, fish, low-fat milk products, and low-fat meat. An average Nordic diet served as the control diet and included low-fiber cereal products, dairy fat-based spreads, regular-fat milk products, and a limited amount of fruits, vegetables, and berries. Lipidomic profiles were measured at baseline, week 12, and the end of the intervention (18 or 24 wk) by using ultraperformance liquid chromatography mass spectrometry. The effects of the diets on the lipid variables were analyzed with linear mixed-effects models. Data from centers with 18- or 24-wk duration were also analyzed separately.RESULTS: Changes in 21 plasma lipids differed significantly between the groups at week 12 (false discovery rate P < 0.05), including increases in plasmalogens and decreases in ceramides in the healthy Nordic diet group compared with the control group. At the end of the study, changes in lipidomic profiles did not differ between the groups. However, when the intervention lasted 24 wk, changes in 8 plasma lipids that had been identified at 12 wk, including plasmalogens, were sustained. There were no differences in changes in plasma lipids between groups with an intervention of 18 wk. By the dietary biomarker score, adherence to diet did not explain the difference in the results related to the duration of the study.CONCLUSIONS: A healthy Nordic diet transiently modified the plasma lipidomic profile, specifically by increasing the concentrations of antioxidative plasmalogens and decreasing insulin resistance-inducing ceramides. This trial was registered at clinicaltrials.gov as NCT00992641.
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