| 1. |
- Fridén, Michael, et al.
(författare)
-
Associations between fatty acid composition in serum cholesteryl esters and liver fat, basal fat oxidation, and resting energy expenditure : a population-based study
- 2021
-
Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 114:5, s. 1743-1751
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We have repeatedly shown in short-term feeding trials that a high intake of dietary n-6 PUFAs, i.e. linoleic acid, prevents liver fat accumulation compared with saturated fat. However, population-based data is lacking and the mechanisms behind such effects are unclear.OBJECTIVE: To investigate associations between serum cholesteryl ester (CE) fatty acids and liver fat, basal fat oxidation [respiratory quotient (RQ)], and resting energy expenditure (REE). We hypothesized that PUFA in particular is inversely associated with liver fat and that such a relation is partly explained by a PUFA-induced increase in basal fat oxidation or REE.METHODS: Cross-sectional analyses using linear regression models in a population-based cohort with data on serum CE fatty acid composition and liver fat (n = 308).RESULTS: Linoleic acid (18:2n-6) (β = -0.03, 95% CI: -0.06, -0.001) and Δ5 desaturase index were inversely associated, whereas, γ-linolenic acid (18:3n-6) (β = 0.59, 95% CI: 0.28, 0.90), dihomo-γ-linolenic acid (20:3n-6) (β = 1.20, 95% CI: 0.65, 1.75), arachidonic acid (20:4n-6) (β = 0.08, 95% CI: 0.002, 0.16), palmitoleic acid (16:1n-7) (β = 0.37, 95% CI: 0.04, 0.70), Δ6 desaturase, and stearoyl CoA desaturase-1 (SCD-1) index were directly associated with liver fat after adjustment for confounders. Several serum CE fatty acids were correlated with both liver fat and REE, but only the association between DHA (22:6n-3) and liver fat was clearly attenuated after adjustment for REE (from β = -0.63 95% CI: -1.24, -0.02 to β = -0.34, 95% CI: -0.95, 0.27). Palmitoleic acid and SCD-1 were weakly inversely correlated with RQ but could not explain a lower liver fat content.CONCLUSIONS: Several serum CE fatty acids are associated with liver fat, among them linoleic acid. Although we identified novel associations between individual fatty acids and RQ and REE, our findings imply that PUFAs might prevent liver fat accumulation through mechanisms other than enhanced whole-body energy metabolism.
|
|
| 2. |
- Fridén, Michael, et al.
(författare)
-
Diet composition, nutrient substitutions and circulating fatty acids in relation to ectopic and visceral fat depots
- 2023
-
Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 42:10, s. 1922-1931
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Short-term randomized trials have demonstrated that replacing saturated fat (SFA) with polyunsaturated fat (PUFA) causes a reduction or prevention of liver fat accumulation, but population-based studies on diet and body fat distribution are limited. We investigated cross-sectional associations between diet, circulating fatty acids and liver fat, visceral adipose tissue (VAT), intermuscular adipose tissue (IMAT) and other fat depots using different energy-adjustment models.METHODS: Sex-stratified analyses of n = 9119 (for serum fatty acids) to 13 849 (for nutrients) participants in UK Biobank were conducted. Fat depots were assessed by MRI, circulating fatty acids by NMR spectroscopy and diet by repeated 24-h recalls. Liver fat, VAT and IMAT were primary outcomes; total adipose tissue (TAT) and abdominal subcutaneous adipose tissue (ASAT) were secondary outcomes. Three a priori defined models were constructed: the all-components model, standard model and leave-one-out model (main model including specified nutrient substitutions). Imiomics (MRI-derived) was used to confirm and visualize associations.RESULTS: In women, substituting carbohydrates and free sugars with saturated fat (SFA) was positively associated with liver fat (β (95% CI) = 0.19 (0.02, 0.36) and β (95% CI) = 0.20 (0.05-0.35), respectively) and IMAT (β (95% CI) = 0.07 (0.00, 0.14) and β (95% CI) = 0.08 (0.02, 0.13), respectively), whereas substituting animal fat with plant fat was inversely associated with IMAT, ASAT and TAT. In the all-components and standard models, SFA and animal fat were positively associated with liver fat, IMAT and VAT whereas plant fat was inversely associated with IMAT in women. Few associations were observed in men. Circulating polyunsaturated fatty acids (PUFA) were inversely associated with liver fat, IMAT and VAT in both men and women, whereas SFA and monounsaturated fatty acids were positively associated.CONCLUSIONS: Type of dietary fat may be an important determinant of ectopic fat in humans consuming their habitual diet. Plant fat and PUFA should be preferred over animal fat and SFA. This is corroborated by circulating fatty acids and overall consistent through different energy adjustment models.TWITTER SUMMARY: In UK Biobank, intake of saturated- and animal fat were positively whereas biomarkers of polyunsaturated fat were inversely associated with liver-, visceral- and intermuscular fat. Type of dietary fat may be a determinant of ectopic fat, a risk factor for cardiometabolic disease.
|
|
| 3. |
- Fridén, Michael, et al.
(författare)
-
Intake of Ultra-Processed Food and Ectopic-, Visceral- and Other Fat Depots : A Cross-Sectional Study.
- 2022
-
Ingår i: Frontiers in nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The purpose of this study was to investigate associations between intake of ultra-processed food (UPF) and liver fat, pancreas fat and visceral adipose tissue (VAT) but also subcutaneous adipose tissue (SAT), VAT/SAT ratio and total fat mass.Materials and Methods: Cross-sectional analysis of n = 286 50-year old men and women. Energy percentage (%E) from UPF was calculated from a semi-quantitative food frequency questionnaire. Food items were categorized according to the NOVA-classification system and fat depots were assessed using magnetic resonance imaging (MRI) and bioelectrical impedance analysis (BIA). Associations were analyzed using linear regression, adjusted for sex, education, physical activity, smoking, dietary factors and BMI.Results: Mean intake of UPF was 37.8 ± 10.2 %E and the three largest contributors to this were crisp- and wholegrain breads and spreads, indicating overall healthy food choices. Consumption of UPF was associated with higher intake of energy, carbohydrates and fiber and lower intake of protein and polyunsaturated fat but no differences were observed for total fat, saturated fat (SFA), monounsaturated fat, sugar or alcohol between tertiles of UPF. Intake of UPF was positively associated with liver- and pancreas fat, VAT, VAT/SAT and inversely associated with total fat mass in crude models. The association for VAT remained after full adjustment (β = 0.01 (95% CI: 0.002, 0.02), P = 0.02) and was driven by women.Conclusion: Energy intake from UPF is not associated with ectopic fat, SAT or total fat after adjustment for multiple confounders in this population having overall healthy food habits. However, a positive association between UPF and VAT was observed which was driven by women.
|
|
| 4. |
- Johansson, Hans-Erik, 1960-, et al.
(författare)
-
Energy restriction in obese women suggest linear reduction of hepatic fat content and time-dependent metabolic improvements
- 2019
-
Ingår i: Nutrition & Diabetes. - : Springer Science and Business Media LLC. - 2044-4052. ; 9:1
-
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.
|
|
| 5. |
- Rosqvist, Fredrik, 1985-, et al.
(författare)
-
Abdominal Fat and Metabolic Health Markers but Not PNPLA3 Genotype Predicts Liver Fat Accumulation in Response to Excess Intake of Energy and Saturated Fat in Healthy Individuals
- 2020
-
Ingår i: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Saturated fat (SFA) has consistently been shown to increase liver fat, but the response appears variable at the individual level. Phenotypic and genotypic characteristics have been demonstrated to modify the hypercholesterolemic effect of SFA but it is unclear which characteristics that predict liver fat accumulation in response to a hypercaloric diet high in SFA.Objective: To identify predictors of liver fat accumulation in response to an increased intake of SFA.Design: We pooled our two previously conducted double-blind randomized trials (LIPOGAIN and LIPOGAIN-2, clinicaltrials.gov NCT01427140 and NCT02211612) and used data from the n = 49 metabolically healthy men (n = 32) and women (n = 17) randomized to a hypercaloric diet through addition of SFA-rich muffins for 7-8 weeks. Associations between clinical and metabolic variables at baseline and changes in liver fat during the intervention were analyzed using Spearman rank correlation. Linear regression was used to generate a prediction model.Results: Liver fat increased by 33% (IQR 5.4-82.7%; P < 0.0001) in response to excess energy intake and this was not associated (r = 0.17, P = 0.23) with the increase in body weight (1.9 kg; IQR 1.1-2.9 kg). Liver fat accumulation was similar (P = 0.28) in carriers (33%, IQR 14-79%) and non-carriers (33%, IQR -11 to +87%) of the PNPLA3-I148M variant. Baseline visceral and liver fat content, as well as levels of the liver enzyme gamma-glutamyl transferase (GT), were the strongest positive predictors of liver fat accumulation-in contrast, adiponectin and the fatty acid 17:0 in adipose tissue were the only negative predictors in univariate analyses. A regression model based on eight clinical and metabolic variables could explain 81% of the variation in liver fat accumulation.Conclusion: Our results suggest there exists a highly inter-individual variation in the accumulation of liver fat in metabolically healthy men and women, in response to an increased energy intake from SFA and carbohydrates that occurs over circa 2 months. This marked variability in liver fat accumulation could largely be predicted by a set of clinical (e.g., GT and BMI) and metabolic (e.g., fatty acids, HOMA-IR, and adiponectin) variables assessed at baseline.
|
|
| 6. |
- Rosqvist, Fredrik, 1985-, et al.
(författare)
-
Fatty acid composition in serum cholesterol esters and phospholipids is linked to visceral and subcutaneous adipose tissue content in elderly individuals : a cross-sectional study
- 2017
-
Ingår i: Lipids in Health and Disease. - : Springer Science and Business Media LLC. - 1476-511X. ; 16, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Visceral adipose tissue (VAT) and truncal fat predict cardiometabolic disease. Intervention trials suggest that saturated fatty acids (SFA), e. g. palmitic acid, promote abdominal and liver fat storage whereas polyunsaturated fatty acids (PUFA), e. g. linoleic acid, prevent fat accumulation. Such findings require investigation in population-based studies of older individuals. We aimed to investigate the relationships of serum biomarkers of PUFA intake as well as serum levels of palmitic acid, with abdominal and total adipose tissue content.Methods: In a population-based sample of 287 elderly subjects in the PIVUS cohort, we assessed fatty acid composition in serum cholesterol esters (CE) and phospholipids (PL) by gas chromatography and the amount of VAT and abdominal subcutaneous (SAT) adipose tissue by magnetic resonance imaging (MRI), liver fat by MR spectroscopy (MRS), and total body fat, trunk fat and leg fat by dual-energy X-ray absorptiometry (DXA). Insulin resistance was estimated by HOMA-IR.Results: VAT and trunk fat showed the strongest correlation with insulin resistance (r = 0.49, P < 0.001). Linoleic acid in both CE and PL was inversely related to all body fat depots (r = -0.24 to -0.33, P < 0.001) including liver fat measured in a sub-group (r = -0.26, P < 0.05, n = 73), whereas n-3 PUFA showed weak inverse (18: 3n-3) or positive (20: 5n-3) associations. Palmitic acid in CE, but not in PL, was directly correlated with VAT (r = 0.19, P < 0.001) and trunk fat (r = 0.18, P = 0.003). Overall, the significant associations remained after adjusting for energy intake, height, alcohol, sex, smoking, education and physical activity. The inverse correlation between linoleic acid and VAT remained significant after further adjustment for total body fat.Conclusions: Serum linoleic acid is inversely related to body fat storage including VAT and trunk fat whereas palmitic acid was less consistently but directly associated, in line with recent feeding studies. Considering the close link between VAT and insulin resistance, a potential preventive role of plant-based PUFA in VAT accumulation warrants further study.
|
|
| 7. |
- Rosqvist, Fredrik, 1985-, et al.
(författare)
-
Overeating saturated fat promotes fatty liver and ceramides compared to polyunsaturated fat : a randomized trial
- 2019
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 104:12, s. 6207-6219
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Saturated fat (SFA) versus polyunsaturated fat (PUFA) may promote non-alcoholic fatty liver disease (NAFLD) by yet unclear mechanisms.OBJECTIVE: To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.DESIGN: Double-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction.SETTING: General community.Participants: n=61 overweight or obese men and women.INTERVENTION: Muffins high in either palm (SFA)- or sunflower oil (PUFA) were added to the habitual diet.MAIN OUTCOME MEASURE: Lean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots.RESULTS: By design, body weight gain was similar in SFA (2.31±1.38 kg) and PUFA (2.01±1.90 kg) groups, P=0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat or total body fat compared with PUFA. SFA consistently increased, while PUFA reduced circulating ceramides; changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction.CONCLUSIONS: Saturated fat markedly induces liver fat and serum ceramides whereas dietary polyunsaturated fat prevent liver fat accumulation, reduce ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.
|
|
| 8. |
- Rosqvist, Fredrik, 1985-, et al.
(författare)
-
Overfeeding polyunsaturated fat compared to saturated fat does not differentially influence lean tissue accumulation in overweight individuals : a randomized controlled trial
- 2024
-
Ingår i: American Journal of Clinical Nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. ; 120:1, s. 121-128
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fatty acids may influence lean tissue volume and skeletal muscle function. We previously reported in young lean participants that overfeeding polyunsaturated fat (PUFA) compared with saturated fat (SFA) induced greater lean tissue accumulation despite similar weight gain.OBJECTIVE: In a double-blind randomized controlled trial (RCT), we aimed to investigate if the differential effects of overfeeding SFA and PUFA on lean tissue accumulation could be replicated in individuals with overweight, and identify potential determinants. Further, using substitution models, we investigated associations between SFA and PUFA levels with lean tissue volume, in a large population-based sample (UK Biobank).METHODS: Sixty-one males and females with overweight (BMI 27.3 (interquartile range 25.4 to 29.3), age 43 (interquartile range 36 to 48)) were overfed SFA (palm oil) or n-6 PUFA (sunflower oil) for 8 weeks. Lean tissue was assessed by magnetic resonance imaging (MRI). We had access to n=13849 participants with data on diet, covariates and MRI measurements of lean tissue, as well as 9119 participants with data on circulating fatty acids, in the UK Biobank.RESULTS: Body weight gain (mean±SD) was similar in PUFA (2.01±1.90 kg) and SFA (2.31±1.38 kg) groups. Lean tissue increased to a similar extent (0.54±0.93 L and 0.67±1.21 L for PUFA and SFA group, respectively, with a difference between groups of 0.07 (-0,21, 0,35)). We observed no differential effects on circulating amino acids, myostatin or interleukin-15 and no clear determinants of lean tissue accumulation. Similar non-significant results for SFA and PUFA were observed in UK Biobank, but circulating fatty acids demonstrated ambiguous and sex-dependent associations.CONCLUSION: Overfeeding SFA or PUFA does not differentially affect lean tissue accumulation during 8 weeks in individuals with overweight. A lack of dietary fat type-specific effects on lean tissue is supported by specified substitution models in a large population-based cohort consuming their habitual diet.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02211612.
|
|
| 9. |
- Straniero, S., et al.
(författare)
-
Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity
- 2017
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 281:5, s. 507-517
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundBile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver.MethodsTen morbidly obese women (BMI 42 ± 2.6 kg m−2) were monitored on days 0, 3, 7, 14 and 28 after beginning a low‐calorie diet (800–1100 kcal day−1). Serum was collected and liver size and fat content determined. Synthesis of BAs and cholesterol was evaluated from serum markers, and the serum levels of lipoproteins, BAs, proprotein convertase subtilisin/kexin type 9 (PCSK9), insulin, glucose and FGF19 were monitored. Fifty‐four nonobese women (BMI <25 kg m−2) served as controls.ResultsAt baseline, synthesis of both BAs and cholesterol and serum levels of BAs and PCSK9 were elevated in the obese group compared to controls. Already after 3 days on a low‐calorie diet, BA and cholesterol synthesis and serum BA and PCSK9 levels normalized, whereas LDL cholesterol increased. FGF19 and triglyceride levels were unchanged, and liver volume was reduced by 10%.ConclusionsThe results suggest that hepatic BAs and cholesterol are deficient in morbid obesity. Caloric restriction rapidly counteracts these deficiencies, normalizing BA and cholesterol synthesis and circulating PCSK9 levels, indicating that overproduction of cholesterol in enlarged peripheral tissues cannot explain this phenotype. We propose that excessive food intake promotes faecal loss of BAs and cholesterol contributing to their hepatic deficiencies.
|
|
