| 1. |
- Fridén, Michael, et al.
(författare)
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Hepatic Unsaturated Fatty Acids Are Linked to Lower Degree of Fibrosis in Non-alcoholic Fatty Liver Disease
- 2022
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The hepatic lipidome of patients with early stages of non-alcoholic fatty liver disease (NAFLD) has been fairly well-explored. However, studies on more progressive forms of NAFLD, i.e., liver fibrosis, are limited. Materials and methods: Liver fatty acids were determined in cholesteryl esters (CE), phospholipids (PL), and triacylglycerols (TAG) by gas chromatography. Cross-sectional associations between fatty acids and biopsy-proven NAFLD fibrosis (n = 60) were assessed using multivariable logistic regression models. Stages of fibrosis were dichotomized into none-mild (F0–1) or significant fibrosis (F2–4). Models were adjusted for body-mass index (BMI), age and patatin-like phospholipase domain-containing protein 3 (PNPLA3 rs738409) (I148M) genotype. A secondary analysis examined whether associations from the primary analysis could be confirmed in the corresponding plasma lipid fractions. Results: PL behenic acid (22:0) was directly associated [OR (95% CI): 1.86 (1.00, 3.45)] whereas PL docosahexaenoic acid (22:6n-3) [OR (95% CI): 0.45 (0.23, 0.89)], TAG oleic acid (18:1n-9) [OR (95% CI): 0.52 (0.28, 0.95)] and 18:1n-9 and vaccenic acid (18:1n-7) (18:1) [OR (95% CI): 0.52 (0.28, 0.96)] were inversely associated with liver fibrosis. In plasma, TAG 18:1n-9 [OR (95% CI): 0.55 (0.31, 0.99)], TAG 18:1 [OR (95% CI): 0.54 (0.30, 0.97)] and PL 22:0 [OR (95% CI): 0.46 (0.25, 0.86)] were inversely associated with liver fibrosis. Conclusion: Higher TAG 18:1n-9 levels were linked to lower fibrosis in both liver and plasma, possibly reflecting an altered fatty acid metabolism. Whether PL 22:6n-3 has a protective role, together with a potentially adverse effect of hepatic 22:0, on liver fibrosis warrants large-scale studies.
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| 2. |
- Rosqvist, Fredrik, 1985-, et al.
(författare)
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Fatty acids in multiple circulating lipid fractions reflects the composition of liver triglycerides in humans
- 2022
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 1532-1983 .- 0261-5614. ; 41:4, s. 805-809
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Fatty acids (e.g. 16:1n-7) and desaturase indices (e.g. stearoyl-CoA desaturase, SCD) in plasma cholesteryl esters (CE) and phospholipids (PL) are used as biomarkers of dietary fat quality and lipid metabolism and are associated with disease outcomes. Endogenously produced circulating fatty acids are believed to reflect composition of the liver, yet little data exist to support such relationship. We investigated associations between circulating fatty acids and fatty acids within the liver. Methods: Liver biopsies and blood were collected from n = 60 patients with non-alcoholic fatty liver disease. Fatty acids in CE, PL and triglycerides (TG) in plasma and liver were analyzed using gas chromatography. Associations were assessed using Spearman rank correlations. Results: Overall, fatty acids and desaturase indices in plasma PL and TG showed moderate–strong correlations with fatty acids and desaturase indices in corresponding lipid fractions in liver. For plasma CE, 16:1n-7 and SCD were correlated with 16:1n-7 and SCD in liver CE. Noteworthy, fatty acids in plasma CE and PL also showed moderate–strong correlations with fatty acids in liver TG (e.g. r = 0.82–0.87 for 16:1n-7 and r = 0.77 for SCD). Conclusion: We demonstrate that fatty acids in circulating lipid fractions, including CE, TG and PL, reflects the composition of liver TG in humans, suggesting that circulating fatty acids might be useful biomarkers for the fatty acid composition of the liver. As liver tissue is rarely available in cohort studies, our findings could enhance our understanding of plasma fatty acids as markers of hepatic lipid metabolism and their links to metabolic diseases.
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| 3. |
- Fridén, Michael, et al.
(författare)
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Effects of a low-carbohydrate high polyunsaturated fat diet or a healthy Nordic diet versus usual care on liver fat content and cardiometabolic risk factors in people with type 2 diabetes and prediabetes: a randomized controlled trial (NAFLDiet)
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Previous trials have shown that plant-derived polyunsaturated fatty acids (PUFA) in place of saturated fat reduces liver fat, a prerequisite for non-alcoholic fatty liver disease (NAFLD). The effect on liver fat from a novel “anti-lipogenic diet” replacing carbohydrates with PUFA or a healthy Nordic diet (HND) higher in whole-grains but lower in saturated fat has not yet been examined. Objectives: To investigate the effects on changes in liver fat (primary outcome) and other cardiometabolic risk factors after 12 months of follow-up in individuals with prediabetes or T2D from three different diet comparisons: a low carbohydrate high PUFA (LCPUFA) diet versus a HND, a LCPUFA diet versus usual care (UC) and a HND versus UC. Methods: A three-arm parallel ad libitum randomized trial was conducted. Adult men and women (n=148) were randomized to one of the three diet groups. Participants in all groups received key food items on a monthly/bimonthly basis. Liver fat and cardiometabolic risk factors were assessed at baseline and after 12 months. Dietary adherence was assessed using weighed food diaries and objective biomarkers. General linear models were employed to estimate the intention-to-treat (ITT) effect. Results: Dietary adherence was high for all diet groups. Liver fat was reduced to a similar extent in the LCPUFA and the HND group compared to UC (-1.46% (95% CI: -2.42, -0.51)) and -1.76 % (95% CI: -2.96, -0.57), respectively. No difference in liver fat between LCPUFA and HND was observed. Body weight and HbA1c decreased more in the HND compared to the other diet groups whereas no differences were observed between LCPUFA and UC. Similar reductions in LDL-cholesterol were observed for the HND and the LCPUFA group compared to UC, but only the HND reduced triglycerides and C-reactive protein (CRP) compared with UC. No differences were observed for any other secondary outcomes.Conclusions: A LCPUFA diet and a HND both reduced liver fat as compared with UC. Given the sustained weight loss after the HND compared to the other groups, together with improvements in other cardiometabolic markers, the HND in particular seems to be useful for the treatment of T2D and NAFLD.
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| 4. |
- Rosqvist, Fredrik, 1985-, et al.
(författare)
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Circulating fatty acids from high-throughput metabolomics platforms as potential biomarkers of dietary fatty acids
- 2022
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 41:12, s. 2637-2643
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Tidskriftsartikel (refereegranskat)abstract
- Background Some fatty acids, i.e. n-3 and n-6 polyunsaturated fatty acids (PUFA), from metabolomics platforms based on nuclear magnetic resonance imaging (NMR) or liquid chromatography mass-spectrometry (LC-MS) are suggested to reflect dietary exposure. NMR and LC-MS are both relatively fast and cheap, however few studies have investigated their validity. Linoleic acid (LA) and docosahexaenoic acid (DHA), measured using gas chromatography (GC), are established biomarkers of dietary n-6 and n-3 PUFA intake, respectively.Objective To examine if circulating fatty acids derived from two commonly applied metabolomics platforms (using NMR and LC-MS) provide similar information compared to GC in two pooled population-based cohorts, one patient cohort, and in a randomized controlled trial (RCT).Methods Spearman rank correlations were conducted between LA and DHA in cholesteryl esters (CE) from GC and whole serum/plasma LA and DHA from the metabolomics platforms in a pooled population-based cohort of men and women (n ˜ 1100) (primary analysis). Secondary correlation analyses included fatty acid classes such as n-3 PUFA, n-6 PUFA, saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and total PUFA. Additionally, correlations were investigated for LA, DHA and the five fatty acid classes in phospholipids (PL), triacylglycerols (TAG) and non-esterified fatty acids (NEFA) in a RCT of n = 60 as well as in a population with biopsy-verified non-alcoholic fatty liver disease (NAFLD) (n = 59). Misclassification was examined using cross-tabulation and visualized using alluvial plots.Results Moderate to strong correlations (r = 0.51–0.81) were observed for LA and DHA in multiple lipid fractions in all cohorts using the NMR platform. For the pooled cohort, LA (r = 0.67, P < 0.0001) and DHA (r = 0.68, P < 0.0001) assessed in CE were strongly correlated with LA and DHA derived using NMR. Nearly half (49%) were correctly classified into their respective quartiles. Using LC-MS, only DHA (r = 0.44, P < 0.0001) demonstrated moderate correlations with DHA from GC.Conclusions Unless fatty acid data from GC analysis is available or feasible, NMR-based technology might be a better option than a LC-MS-based platform, at least for certain PUFA. This should be taken into account in future studies aiming to use circulating fatty acids as dietary biomarkers for the investigation of diet-disease relationships.
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| 5. |
- 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. - : Elsevier. - 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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| 6. |
- Retterstøl, Kjetil, et al.
(författare)
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Fat and fatty acids : a scoping review for Nordic Nutrition Recommendations 2023
- 2024
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Ingår i: Food & Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 68
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Forskningsöversikt (refereegranskat)abstract
- Two de novo NNR2022 systematic reviews (SRs) as well as 21 qualified SRs (qSRs) were available. A literature search yielded an additional ~70 SRs, meta-analyses and biomarker papers. Diets lower in total fat are associated with reductions in body weight and blood pressure compared with diets higher in total fat in adults. Partial replacement of saturated fatty acid (SFA) with n-6 polyunsaturated fatty acid (PUFA) improves blood lipid profile, decreases the risk of cardiovascular disease (CVD), improves glucose-insulin homeostasis and may decrease the risk of total mortality. Long-chain n-3 PUFAs (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) decrease triglycerides and are associated with lower risk of CVD. Dietary PUFAs, both n-3 and n-6, may be associated with reduced risk of type 2 diabetes (T2D). There is inconclusive evidence to suggest that the type of dietary fat is associated with blood pressure, risk of hypertension or musculoskeletal health. Higher intake of total PUFA is associated with lower mortality from any cancer. Long-chain n-3 PUFA is associated with reduced risk of breast cancer, whereas biomarker levels of n-6 PUFA are associated with lower risk of any cancer. Intake of long-chain n-3 PUFA during pregnancy increases length of gestation and child birth weight and reduces the risk of preterm delivery, but there is inconclusive evidence to suggest that it may influence child neurodevelopment, growth or development of allergic disease. In studies with higher versus lower dietary cholesterol intake levels, total blood cholesterol increased or were unaffected by the dietary cholesterol, resulting in inconclusive results. Trans fatty acid (TFA), regardless of source, impairs blood lipid profile compared to unsaturated fat. In observational studies, TFA is positively associated with CVD and total mortality but whether associations differ by source is inconclusive. Ruminant TFA, as well as biomarker levels of odd-chain fatty acids, might be associated with lower risk of T2D.
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| 7. |
- 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. ; 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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| 8. |
- Leder, Lena, et al.
(författare)
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Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome : A SYSDIET sub-study
- 2016
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Ingår i: Genes & Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diet has a great impact on the risk of developing features of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD). We evaluated whether a long-term healthy Nordic diet (ND) can modify the expression of inflammation and lipid metabolism-related genes in peripheral blood mononuclear cells (PBMCs) during a 2-h oral glucose tolerance test (OGTT) in individuals with MetS. Methods: A Nordic multicenter randomized dietary study included subjects (n = 213) with MetS, randomized to a ND group or a control diet (CD) group applying an isocaloric study protocol. In this sub-study, we included subjects (n = 89) from three Nordic centers: Kuopio (n =26), Lund (n = 30), and Oulu (n = 33) with a maximum weight change of ±4 kg, high-sensitivity C-reactive protein concentration ≤10 mg L-1, and baseline body mass index -2. PBMCs were isolated, and the mRNA gene expression analysis was measured by quantitative real-time polymerase chain reaction (qPCR). We analyzed the mRNA expression changes of 44 genes before and after a 2hOGTT at the beginning and the end of the intervention. Results: The healthy ND significantly down-regulated the expression of toll-like receptor 4 (TLR4), interleukin 18 (IL18), and thrombospondin receptor (CD36) mRNA transcripts and significantly up-regulated the expression of peroxisome proliferator-activated receptor delta (PPARD) mRNA transcript after the 2hOGTT compared to the CD. Conclusions: A healthy ND is able to modify the gene expression in PBMCs after a 2hOGTT. However, more studies are needed to clarify the biological and clinical relevance of these findings.
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| 9. |
- Eichelmann, Fabian, et al.
(författare)
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Lipidome changes due to improved dietary fat quality inform cardiometabolic risk reduction and precision nutrition
- 2024
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Ingår i: Nature Medicine. - 1078-8956 .- 1546-170X. ; In Press
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Tidskriftsartikel (refereegranskat)abstract
- Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabolite concentrations. In the EPIC-Potsdam cohort, a difference in the MLS, reflecting better dietary fat quality, was associated with a significant reduction in the incidence of cardiovascular disease (−32%; 95% confidence interval (95% CI): −21% to −42%) and type 2 diabetes (−26%; 95% CI: −15% to −35%). We built a closely correlated simplified score, reduced MLS (rMLS), and observed that beneficial rMLS changes, suggesting improved dietary fat quality over 10 years, were associated with lower diabetes risk (odds ratio per standard deviation of 0.76; 95% CI: 0.59 to 0.98) in the Nurses’ Health Study. Furthermore, in the PREDIMED trial, an olive oil-rich Mediterranean diet intervention primarily reduced diabetes incidence among participants with unfavorable preintervention rMLS levels, suggestive of disturbed lipid metabolism before intervention. Our findings indicate that the effects of dietary fat quality on the lipidome can contribute to a more precise understanding and possible prediction of the health outcomes of specific dietary fat modifications.
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| 10. |
- Fridén, Michael, et al.
(författare)
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Substitutions of saturated fat intakes with other macronutrients and foods and risk of NAFLD cirrhosis and all-cause hepatocellular carcinoma : a prospective cohort study
- 2024
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. ; 120:1, s. 187-195
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundShort-term trials have shown a reduction in liver fat when saturated fatty acids (SFAs) are substituted with polyunsaturated fatty acids (PUFA), or with low-glycemic carbohydrates. However, few cohort studies have been conducted to investigate the associations of replacing SFA and SFA-rich foods with different macronutrients and foods in more severe stages of liver disease; nonalcoholic fatty liver disease (NAFLD) cirrhosis and hepatocellular carcinoma (HCC).ObjectivesTo investigate associations between the substitution of SFA and SFA-rich foods with other macronutrients and foods and NAFLD cirrhosis and HCC in a middle-aged to elderly Swedish population of n = 77,059 males and females.MethodsTime-to-event analyses were performed to investigate associations between the food and macronutrient substitutions and NAFLD cirrhosis and HCC. Multivariable Cox regression models were constructed to estimate hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Statistical isocaloric and equal-mass substitutions were performed using the leave-one-out method. Prespecified nutrient and food substitutions of interest were SFA with carbohydrates, SFA with fiber, SFA with PUFA, butter with margarine and vegetable oils, unprocessed red meat with fish, and milk with fermented milk.ResultsOver a median follow-up of 24 y, 566 cases of NAFLD cirrhosis and 205 cases of HCC were registered. Overall, dietary substitutions showed no clear associations with either NAFLD cirrhosis or HCC. Substituting SFA with carbohydrates showed an HR of 0.87 (95% CI: 0.74, 1.02) for HCC and 1.00 (95% CI: 0.89, 1.11) for NAFLD cirrhosis. Substituting milk with fermented milk showed an HR of 0.93 (95% CI: 0.85, 1.01) for HCC and 0.97 (95% CI: 0.92, 1.03) for NAFLD cirrhosis.ConclusionsNo clear associations were observed between diet and NAFLD cirrhosis or HCC. Although accompanied by low precision, possible lowered risks of HCC by substituting SFA with carbohydrates or milk with fermented milk might be of interest, but needs replication in other cohorts.
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