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Sökning: WFRF:(Hakkarainen A.)

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  • Sevastianova, K., et al. (författare)
  • Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans
  • 2012
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 96:4, s. 727-734
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cross-sectional studies have identified a high intake of simple sugars as an important dietary factor predicting nonalcoholic fatty liver disease (NAFLD). Objective: We examined whether overfeeding overweight subjects with simple sugars increases liver fat and de novo lipogenesis (DNL) and whether this is reversible by weight loss. Design: Sixteen subjects [BMI (kg/m(2)): 30.6 +/- 1.2] were placed on a hypercaloric diet (>1000 kcal simple carbohydrates/d) for 3 wk and, thereafter, on a hypocaloric diet for 6 mo. The subjects were genotyped for rs739409 in the PNPLA3 gene. Before and after overfeeding and after hypocaloric diet, metabolic variables and liver fat (measured by proton magnetic resonance spectroscopy) were measured. The ratio of palmitate (16:0) to linoleate (18:2n-6) in serum and VLDL triglycerides was used as an index of DNL. Results: Carbohydrate overfeeding increased weight (+/- SEM) by 2% (1.8 +/- 0.3 kg; P < 0.0001) and liver fat by 27% from 9.2 +/- 1.9% to 11.7 +/- 1.9% (P = 0.005). DNL increased in proportion to the increase in liver fat and serum triglycerides in subjects with PNPLA3-148II but not PNPLA3-148MM. During the hypocaloric diet, the subjects lost 4% of their weight (3.2 +/- 0.6 kg; P < 0.0001) and 25% of their liver fat content (from 11.7 +/- 1.9% to 8.8 +/- 1.8%; P < 0.05). Conclusions: Carbohydrate overfeeding for 3 wk induced a >10-fold greater relative change in liver fat (27%) than in body weight (2%). The increase in liver fat was proportional to that in DNL. Weight loss restores liver fat to normal. These data indicate that the human fatty liver avidly accumulates fat during carbohydrate overfeeding and support a role for DNL in the pathogenesis of NAFLD. This trial was registered at www.hus.fi as 235780. Am J Clin Nutr 2012;96:727-34.
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  • Naukkarinen, J., et al. (författare)
  • Characterising metabolically healthy obesity in weight-discordant monozygotic twins
  • 2014
  • Ingår i: Diabetologia. - New York, USA : Springer. - 0012-186X .- 1432-0428. ; 57:1, s. 167-176
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: Not all obese individuals display the metabolic disturbances commonly associated with excess fat accumulation. Mechanisms maintaining this ‘metabolically healthy obesity’ (MHO) are as yet unknown. We aimed to study different fat depots and transcriptional pathways in subcutaneous adipose tissue (SAT) as related to the MHO phenomenon.Methods: Sixteen rare young adult obesity-discordant monozygotic (MZ) twin pairs (intra-pair difference (∆) in BMI ≥3 kg/m2), aged 22.8–35.8 years, were examined for detailed characteristics of metabolic health (subcutaneous, intra-abdominal and liver fat [magnetic resonance imaging/spectroscopy]), OGTT, lipids, adipokines and C-reactive protein (CRP). Affymetrix U133 Plus 2.0 chips were used to analyse transcriptomics pathways related to mitochondrial function and inflammation in SAT.Results: Based on liver fat accumulation, two metabolically different subgroups emerged. In half (8/16) of the pairs (∆weight 17.1 ± 2.0 kg), the obese co-twin had significantly higher liver fat (∆718%), 78% increase in AUC insulin during OGTT and CRP, significantly more disturbance in the lipid profile and greater tendency for hypertension compared with the lean co-twin. In these obese co-twins, SAT expression of mitochondrial oxidative phosphorylation, branched-chain amino acid catabolism, fatty acid oxidation and adipocyte differentiation pathways were downregulated and chronic inflammation upregulated. In the other eight pairs (∆weight 17.4 ± 2.8 kg), the obese co-twin did not differ from the non-obese co-twin in liver fat (∆8%), insulin sensitivity, CRP, lipids, blood pressure or SAT transcriptomics.Conclusions/interpretation: Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in SAT are associated with low liver fat and MHO.
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  • Heinonen, S., et al. (författare)
  • Mitochondria-related transcriptional signature is downregulated in adipocytes in obesity: a study of young healthy MZ twins
  • 2017
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 60:1, s. 169-181
  • Tidskriftsartikel (refereegranskat)abstract
    • Low mitochondrial activity in adipose tissue is suggested to be an underlying factor in obesity and its metabolic complications. We aimed to find out whether mitochondrial measures are downregulated in obesity also in isolated adipocytes. We studied young adult monozygotic (MZ) twin pairs discordant (n = 14, intrapair difference Delta BMI ae 3 kg/m(2)) and concordant (n = 5, Delta BMI
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  • Matikainen, N., et al. (författare)
  • Fructose intervention for 12 weeks does not impair glycemic control or incretin hormone responses during oral glucose or mixed meal tests in obese men
  • 2017
  • Ingår i: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753. ; 27:6, s. 534-542
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. Methods and results: As many as 66 obese (BMI 26-40 kg/m(2)) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). Conclusion: In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge. (C) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
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  • Taskinen, M. R., et al. (författare)
  • Adverse effects of fructose on cardiometabolic risk factors and hepatic lipid metabolism in subjects with abdominal obesity
  • 2017
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 282, s. 187-201
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017 The Association for the Publication of the Journal of Internal Medicine Background: Overconsumption of dietary sugars, fructose in particular, is linked to cardiovascular risk factors such as type 2 diabetes, obesity, dyslipidemia and nonalcoholic fatty liver disease. However, clinical studies have to date not clarified whether these adverse cardiometabolic effects are induced directly by dietary sugars, or whether they are secondary to weight gain. Objectives: To assess the effects of fructose (75 g day −1 ), served with their habitual diet over 12 weeks, on liver fat content and other cardiometabolic risk factors in a large cohort (n = 71) of abdominally obese men. Methods: We analysed changes in body composition, dietary intake, an extensive panel of cardiometabolic risk markers, hepatic de novo lipogenesis (DNL), liver fat content and postprandial lipid responses after a standardized oral fat tolerance test (OFTT). Results: Fructose consumption had modest adverse effects on cardiometabolic risk factors. However, fructose consumption significantly increased liver fat content and hepatic DNL and decreased β-hydroxybutyrate (a measure of β-oxidation). The individual changes in liver fat were highly variable in subjects matched for the same level of weight change. The increase in liver fat content was significantly more pronounced than the weight gain. The increase in DNL correlated positively with triglyceride area under the curve responses after an OFTT. Conclusion: Our data demonstrated adverse effects of moderate fructose consumption for 12 weeks on multiple cardiometabolic risk factors in particular on liver fat content despite only relative low increases in weight and waist circumference. Our study also indicates that there are remarkable individual differences in susceptibility to visceral adiposity/liver fat after real-world daily consumption of fructose-sweetened beverages over 12 weeks.
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  • Gazzotti, Stefano, et al. (författare)
  • DOX mediated synthesis of PLA-co-PS graft copolymers with matrix-driven self-assembly in PLA-based blends
  • 2022
  • Ingår i: European Polymer Journal. - : Elsevier BV. - 0014-3057 .- 1873-1945. ; 170, s. 111157-
  • Tidskriftsartikel (refereegranskat)abstract
    • Intriguing phase morphology was formed through self-assembly of polylactide-polystyrene (PLA-co-PS) graft copolymers blended with polylactide (PLA). PLA-co-PS graft copolymers were synthesized by exploiting a styrene-functionalized 1,3-Dioxolan-4-one (StyDOX) monomer through a two-step procedure and their structure was confirmed. Different amounts of PLA-co-PS and commercial PLA were solution cast to blend films. Etching of amorphous PLA revealed the presence of spherical micrometer sized domains dispersed within the films, arising from the self-assembly behavior of PLA-co-PS caused by the immiscibility of PS-grafts in the PLA matrix. EDS and IR imaging analyses further revealed that these microspheres were characterized by a PS-rich core opposed to the PLA-rich outer shell, which is expected to be miscible and able to form favorable interactions with the PLA matrix. PLA/PS blends were also prepared with different loadings of PLA-co-PS. The ability of PLA-co-PS to compatibilize the two phases was assessed through rheological analyses. Finally, the possibility to chemically recycle the copolymer was evaluated. 
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