Browsing by Subject "STEATOSIS"

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  • Ydreborg, Magdalena; Lisovskaja, Vera; Lagging, Martin; Christensen, Peer Brehm; Langeland, Nina; Buhl, Mads Rauning; Pedersen, Court; Morch, Kristine; Wejstal, Rune; Norkrans, Gunnar; Lindh, Magnus; Farkkila, Martti; Westin, Johan (2014)
  • Bian, Hua; Hakkarainen, Antti; Zhou, You; Lundbom, Nina; Yki-Järvinen, Hannele (2018)
    Aims: To examine the distribution of liver fat (LFAT) in non-diabetic subjects and test whether the fat in the right as compared to the left lobe correlates better with components of the metabolic syndrome or not. Methods: In this cross sectional study, we determined LFAT by H-1-MRS in the right lobe (LFAT%(MRS)), and by MRI (LFAT%(MRI)) in four regions of interest (ROIs 1-4, two in the right and two in the left lobe) in 97 non-diabetic subjects (age range 22-74 years, BMI 18-41 kg/m(2)) and compared the accuracy of LFAT(MRI) in the different ROIs in diagnosing non-alcoholic fatty liver disease (NAFLD) using areas under the receiver operator characteristic (AUROC) curves. Results: 38% of the subjects had NAFLD (LFAT%(MRS)). LFAT%(MRI) was significantly higher in the right (5.7 +/- 0.5%) than the left (5.1 +/- 0.4%) lobe (p <0.02). The AUROC for LFAT%(MRI) in the right lobe for diagnosing NAFLD was significantly better than that in the left lobe. The relationships between several metabolic parameters and LFAT%(MRI) in the left lobe were significantly worse than those for LFAT%(MRS) while there was no difference between LFAT%(MRS) and right lobe ROIs. Conclusions: Liver right lobe contains more fat and correlates better with components of the metabolic syndrome than the left in non-diabetic subjects. (C) 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
  • Roumans, Kay H. M.; Lindeboom, Lucas; Veeraiah, Pandichelvam; Remie, Carlijn M. E.; Phielix, Esther; Havekes, Bas; Bruls, Yvonne M. H.; Brouwers, Martijn C. G. J.; Stahlman, Marcus; Alssema, Marjan; Peters, Harry P. F.; de Mutsert, Renee; Staels, Bart; Taskinen, Marja-Riitta; Boren, Jan; Schrauwen, Patrick; Schrauwen-Hinderling, Vera B. (2020)
    Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design (ClinicalTrials.gov ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy (H-1-MRS). DNL is positively associated with SFA fraction and is elevated in patients with non-alcoholic fatty liver and type 2 diabetes. Intriguingly, SFA fraction shows a strong, negative correlation with hepatic insulin sensitivity. Our results show that the hepatic lipid composition, as determined by our H-1-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity. Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Here, the authors use H-1-MRS methodology to show hepatic SFA fraction is a measure of DNL and specifically may hamper hepatic insulin sensitivity.
  • Depommier, Clara; Van Hul, Matthias; Everard, Amandine; Delzenne, Nathalie M.; De Vos, Willem M.; Cani, Patrice D. (2020)
    Accumulating evidence points to Akkermansia muciniphila as a novel candidate to prevent or treat obesity-related metabolic disorders. We recently observed, in mice and in humans, that pasteurization of A. muciniphila increases its beneficial effects on metabolism. However, it is currently unknown if the observed beneficial effects on body weight and fat mass gain are due to specific changes in energy expenditure. Therefore, we investigated the effects of pasteurized A. muciniphila on whole-body energy metabolism during high-fat diet feeding by using metabolic chambers. We confirmed that daily oral administration of pasteurized A. muciniphila alleviated diet-induced obesity and decreased food energy efficiency. We found that this effect was associated with an increase in energy expenditure and spontaneous physical activity. Strikingly, we discovered that energy expenditure was enhanced independently from changes in markers of thermogenesis or beiging of the white adipose tissue. However, we found in brown and white adipose tissues that perilipin2, a factor associated with lipid droplet and known to be altered in obesity, was decreased in expression by pasteurized A. muciniphila. Finally, we observed that treatment with pasteurized A. muciniphila increased energy excretion in the feces. Interestingly, we demonstrated that this effect was not due to the modulation of intestinal lipid absorption or chylomicron synthesis but likely involved a reduction of carbohydrates absorption and enhanced intestinal epithelial turnover. In conclusion, this study further dissects the mechanisms by which pasteurized A. muciniphila reduces body weight and fat mass gain. These data also further support the impact of targeting the gut microbiota by using specific bacteria to control whole-body energy metabolism.
  • Petäjä, Elina; Zhou, You; Havana, Marika; Hakkarainen, Antti; Lundbom, Nina; Ihalainen, Jarkko; Yki-Jarvinen, Hannele (2016)
    Insulin-like growth factor binding protein 1 (IGFBP-1) is a potentially interesting marker for liver fat in NAFLD as it is exclusively produced by the liver, and insulin is its main regulator. We determined whether measurement of fasting serum phosphorylated IGFBP-1 (fS-pIGFBP-1) helps to predict liver fat compared to routinely available clinical parameters and PNPLA3 genotype at rs738409. Liver fat content (proton magnetic resonance spectroscopy) was measured in 378 subjects (62% women, age 43 [30-54] years, BMI 32.7 [28.1-39.7] kg/m(2), 46% with NAFLD). Subjects were randomized to discovery and validation groups, which were matched for clinical and biochemical parameters and PNPLA3 genotype. Multiple linear regression and Random Forest modeling were used to identify predictors of liver fat. The final model, % Liver Fat Equation', included age, fS-pIGFBP-1, S-ALT, waist-to-hip ratio, fP-Glucose and fS-Insulin (adjusted R-2 = 0.44 in the discovery group, 0.49 in the validation group, 0.47 in all subjects). The model was significantly better than a model without fS-pIGFBP-1 or S-ALT or S-AST alone. Random Forest modeling identified fS-p-IGFBP-1 as one of the top five predictors of liver fat (adjusted R-2 = 0.39). Therefore, measurement of fS-pIGFBP-1 may help in non-invasive prediction of liver fat content.
  • Rembeck, Karolina; Maglio, Cristina; Lagging, Martin; Christensen, Peer Brehm; Färkkilä, Martti Antero; Langeland, Nina; Buhl, Mads Rauning; Pedersen, Court; Morch, Kristine; Norkrans, Gunnar; Hellstrand, Kristoffer; Lindh, Magnus; Pirazzi, Carlo; Burza, Maria Antonella; Romeo, Stefano; Westin, Johan; NORDynamIC Grp (2012)
  • LITMUS Consortium; Hardy, Timothy; Wonders, Kristy; Younes, Ramy; Aithal, Guruprasad P.; Yki-Järvinen, Hannele (2020)
    Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive liver disease that is closely associated with obesity, type 2 diabetes, hypertension and dyslipidaemia, represents an increasing global public health challenge. There is significant variability in the disease course: the majority exhibit only fat accumulation in the liver but a significant minority develop a necroinflammatory form of the disease (non-alcoholic steatohepatitis, NASH) that may progress to cirrhosis and hepatocellular carcinoma. At present our understanding of pathogenesis, disease natural history and long-term outcomes remain incomplete. There is a need for large, well characterised patient cohorts that may be used to address these knowledge gaps and to support the development of better biomarkers and novel therapies. The European NAFLD Registry is an international, prospectively recruited observational cohort study that aims to establish a large, highly-phenotyped patient cohort and linked bioresource. Here we describe the infrastructure, data management and monitoring plans, and the standard operating procedures implemented to ensure the timely and systematic collection of high-quality data and samples. Already recruiting subjects at secondary/tertiary care centres across Europe, the Registry is supporting the European Union IMI2-funded LITMUS 'Liver Investigation: Testing Marker Utility in Steatohepatitis' consortium, which is a major international effort to robustly validate biomarkers that diagnose, risk stratify and/or monitor NAFLD progression and liver fibrosis stage. The European NAFLD Registry has the demonstrable capacity to support research and biomarker development at scale and pace.
  • Qadri, Sami; Lallukka-Brück, Susanna; Luukkonen, Panu K.; Zhou, You; Gastaldelli, Amalia; Orho-Melander, Marju; Sammalkorpi, Henna; Juuti, Anne; Penttilä, Anne K.; Perttilä, Julia; Hakkarainen, Antti; Lehtimäki, Tiina E.; Oresic, Matej; Hyötyläinen, Tuulia; Hodson, Leanne; Olkkonen, Vesa M.; Yki-Järvinen, Hannele (2020)
    Background & Aims The I148M variant in PNPLA3 is the major genetic risk factor for non-alcoholic fatty liver disease (NAFLD). The liver is enriched with polyunsaturated triglycerides (PUFA-TGs) in PNPLA3-I148M carriers. Gene expression data indicate that PNPLA3 is liver-specific in humans, but whether it functions in adipose tissue (AT) is unknown. We investigated whether PNPLA3-I148M modifies AT metabolism in human NAFLD. Methods Profiling of the AT lipidome and fasting serum non-esterified fatty acid (NEFA) composition was conducted in 125 volunteers (PNPLA3(148MM/MI), n = 63; PNPLA3(148II), n = 62). AT fatty acid composition was determined in 50 volunteers homozygous for the variant (PNPLA3(148MM), n = 25) or lacking the variant (PNPLA3(148II), n = 25). Whole-body insulin sensitivity of lipolysis was determined using [H-2(5)]glycerol, and PNPLA3 mRNA and protein levels were measured in subcutaneous AT and liver biopsies in a subset of the volunteers. Results PUFA-TGs were significantly increased in AT in carriers versus non-carriers of PNPLA3-I148M. The variant did not alter the rate of lipolysis or the composition of fasting serum NEFAs. PNPLA3 mRNA was 33-fold higher in the liver than in AT (P <.0001). In contrast, PNPLA3 protein levels per tissue protein were three-fold higher in AT than the liver (P <.0001) and nine-fold higher when related to whole-body AT and liver tissue masses (P <.0001). Conclusions Contrary to previous assumptions, PNPLA3 is highly abundant in AT. PNPLA3-I148M locally remodels AT TGs to become polyunsaturated as it does in the liver, without affecting lipolysis or composition of serum NEFAs. Changes in AT metabolism do not contribute to NAFLD in PNPLA3-I148M carriers.