This cross sectional study aims to investigate the associations between ectopic lipid accumulation in liver and skeletal muscle and biochemical measures, estimates of insulin resistance, anthropometry, and blood pressure in lean and overweight/obese children.
Fasting plasma glucose, serum lipids, serum insulin, and expressions of insulin resistance, anthropometry, blood pressure, and magnetic resonance spectroscopy of liver and muscle fat were obtained in 327 Danish children and adolescents aged 8-18 years.
In 287 overweight/obese children, the prevalences of hepatic and muscular steatosis were 31% and 68%, respectively, whereas the prevalences in 40 lean children were 3% and 10%, respectively. A multiple regression analysis adjusted for age, sex, body mass index z-score (BMI SDS), and pubertal development showed that the OR of exhibiting dyslipidemia was 4.2 (95%CI: [1.8; 10.2], p = 0.0009) when hepatic steatosis was present. Comparing the simultaneous presence of hepatic and muscular steatosis with no presence of steatosis, the OR of exhibiting dyslipidemia was 5.8 (95%CI: [2.0; 18.6], p = 0.002). No significant associations between muscle fat and dyslipidemia, impaired fasting glucose, or blood pressure were observed. Liver and muscle fat, adjusted for age, sex, BMI SDS, and pubertal development, associated to BMI SDS and glycosylated hemoglobin, while only liver fat associated to visceral and subcutaneous adipose tissue and intramyocellular lipid associated inversely to high density lipoprotein cholesterol.
Hepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased cardiovascular disease risk.
Cites: Child Obes. 2012 Dec;8(6):533-4123181919
Cites: Int J Pediatr Obes. 2011 Aug;6(3-4):188-9621529264
Cites: Int J Obes (Lond). 2014 Jan;38(1):40-523828099
It has been hypothesized that visceral fat releases free fatty acids and adipokines and thereby exposes the liver to fat accumulation. The authors aimed to evaluate current epidemiologic evidence for an association between abdominal fat and liver fat content. Clinical and epidemiologic studies with data on abdominal fat and liver fat content were reviewed. Studies using waist circumference to estimate abdominal fat mass suggested a direct association between abdominal fat and liver fat content. Studies using imaging methods suggested a direct association between intraabdominal fat and liver fat content, but not between subcutaneous abdominal fat and liver fat content. In conclusion, clinical and epidemiologic studies of abdominal fat and liver fat content suggest a direct association between abdominal fat and liver fat content which is probably accounted for by visceral fat. However, results from the included studies do not allow strong conclusions regarding the temporal sequence of events. Future longitudinal studies are recommended to obtain additional information on associations and mechanisms. Both abdominal fat depots and other body compartments of interest should be included to further investigate the association between specific fat depots and liver fat content. Biomarkers may provide insight into underlying mechanisms.
Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. Electronic address: email@example.com.
Noninvasive scoring systems are used to identify persons with advanced liver fibrosis. We investigated the ability of scoring systems to identify individuals in the general population at risk for future liver-related events.
We collected data from the Swedish Apolipoprotein Mortality Risk cohort on persons 35 to 79 years old who had blood samples collected from 1985 through 1996. We collected APRI (n = 127,302), BARD (n = 75,303), FIB-4 (n = 126,941), Forns (n = 122,419), and the nonalcoholic fatty liver disease (NAFLD) fibrosis scores (NFS, n = 13,160). We ascertained incident cases of cirrhosis or complications by linking Swedish health data registers. Cox regression was used to estimate hazard ratios (HRs) for severe liver disease at 5, 10, and a maximum follow-up time of 27 years. The predictive ability of the scores was evaluated using area under the receiver operating characteristic (AUROC) curve and C-statistics analyses. Our specific aims were to investigate the predictive capabilities of scoring systems for fatal and nonfatal liver disease, determine which scoring system has the highest level of accuracy, and investigate the predictive abilities of the scoring systems in persons with a higher probability of NAFLD at baseline.
A similar proportion of individuals evaluated by each scoring system developed cirrhosis or complications thereof (1.0%-1.4%). The incidence of any outcome was increased in intermediate- and high-risk groups compared with low-risk groups, with HRs at 10 years in the high-risk group ranging from 1.67 for the BARD score to 45.9 for the APRI score. The predictive abilities of all scoring systems decreased with time and were higher in men. All scoring systems were more accurate in persons with risk factors for NAFLD at baseline, with AUROCs reaching 0.83.
Higher scores from noninvasive scoring systems to evaluate fibrosis are associated with an increased risk of cirrhosis in a general population, but their predictive ability is modest. Performance was better when patients were followed for shorter time periods and in persons with a higher risk of NAFLD, with AUROC values reaching 0.83. New scoring systems are needed to evaluate risk of fibrosis in the general population and in primary care.
The effects of acquired obesity on lipid profile and lipoprotein composition in rare BMI-discordant monozygotic (MZ) twin pairs were studied.
Abdominal fat distribution, liver fat (magnetic resonance imaging and spectroscopy), fasting serum lipid profile (ultracentrifugation, gradient gel-electrophoresis, and colorimetric enzymatic methods), and lifestyle factors (questionnaires and diaries) were assessed in 15 BMI-discordant (within-pair difference [?] in BMI >3 kg/m2) and nin concordant (?BMI
Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease in the world, but little is known about its potential association with pregnancy outcomes. We aimed to investigate pregnancy outcomes in NAFLD.
The Swedish Medical Birth Register (MBR) was used to identify births between 1992 and 2011 (N = 1 960 416). By linkage with the National Patient Register, we identified women with a diagnosis of NAFLD. The MBR was then used to identify outcomes: gestational diabetes, pre-eclampsia, Caesarean section, Apgar score
Alisma orientale (Sam.) Juzepczuk (Alismataceae) is an indigenous medicinal herb that has been traditionally used for diuretic, hypolipidemic, anti-inflammatory, and antidiabetic proposes in northern and eastern Asia.
This study examined the mechanisms underlying the cytoprotective effect of an aqueous extract of A. orientale (AEAO) against long-chain saturated fatty acid-induced cellular injury.
HepG2 cells were treated with 0.5 mM palmitate to generate a cellular model of nonalcoholic fatty liver disease (NAFLD). Using this cellular model, the cytoprotective effect of AEAO (100 µg/mL) against long-chain saturated fatty acid-induced cellular injury was evaluated by measuring the steatosis, ROS accumulation, and apoptosis.
AEAO significantly attenuated palmitate-induced intracellular steatosis and cellular damage up to 54 and 33%, respectively. Palmitate-induced intracellular levels of reactive oxygen species (ROS) and reactive aldehydes were significantly reduced in the presence of AEAO to 40 and 75%, respectively, suggesting that oxidative stress plays a role in the palmitate-induced damage. AEAO inhibited the palmitate-mediated activation of c-Jun NH(2)-terminal kinase (JNK), a kinase that is correlated with NAFLD. Inhibition of JNK by SP600125 or addition of AEAO significantly reduced palmitate-induced steatosis, ROS accumulation, and apoptosis, indicating that the protective effects of AEAO against palmitate-induced cellular damage result from blocking ROS-activated JNK signaling.
The combined properties of AEAO in cellular steatosis and ROS production are beneficial for treating NAFLD, which includes complex metabolic changes, such that modulation of a single target is often not sufficient to achieve the desired therapeutic effect.
Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is recommended in clinical guidelines. In real-life management, surveillance rates below 20% have been reported from the United States. We aimed to determine the use of HCC-surveillance in patients diagnosed with HCC in a European setting, and to identify the reasons for surveillance failures.
Age, gender, tumour characteristics, BCLC classification, Child-Pugh stage, pre-existing liver disease, treatment, survival, frequency of HCC surveillance and reasons for surveillance failures were retrospectively determined in 616 patients diagnosed with HCC at Karolinska University Hospital 2005-2012.
Hepatitis C, alcoholic liver disease and non-alcoholic fatty liver disease (NAFLD) were the most common diagnoses. The proportion of HCC patients diagnosed through surveillance was 22%. In 35% of cases, surveillance was missed due to doctor's failure to order surveillance or to diagnose the underlying liver disease. Diagnosis of NAFLD or alcoholic liver disease increased the risk of not receiving surveillance more than two-fold. Undiagnosed liver disease was most common in NAFLD patients. Patients who underwent surveillance had smaller tumours, more frequently received curative treatment, and had better survival compared to those in whom surveillance was indicated but missed.
In a European setting, only 22% of HCCs were diagnosed by surveillance, and in more than one-third of cases, surveillance was indicated but missed. NAFLD and alcoholic liver disease were associated with deficient surveillance. Survival was significantly better in patients who underwent surveillance compared with those in whom surveillance was missed although indicated.
There is growing evidence that fruit polyphenols exert beneficial effects on the metabolic syndrome, but the underlying mechanisms remain poorly understood. In the present study, we aimed to analyse the effects of polyphenolic extracts from five types of Arctic berries in a model of diet-induced obesity.
Male C57BL/6 J mice were fed a high-fat/high-sucrose (HFHS) diet and orally treated with extracts of bog blueberry (BBE), cloudberry (CLE), crowberry (CRE), alpine bearberry (ABE), lingonberry (LGE) or vehicle (HFHS) for 8 weeks. An additional group of standard-chow-fed, vehicle-treated mice was included as a reference control for diet-induced obesity. OGTTs and insulin tolerance tests were conducted, and both plasma insulin and C-peptide were assessed throughout the OGTT. Quantitative PCR, western blot analysis and ELISAs were used to assess enterohepatic immunometabolic features. Faecal DNA was extracted and 16S rRNA gene-based analysis was used to profile the gut microbiota.
Treatment with CLE, ABE and LGE, but not with BBE or CRE, prevented both fasting hyperinsulinaemia (mean ± SEM [pmol/l]: chow 67.2?±?12.3, HFHS 153.9?±?19.3, BBE 114.4?±?14.3, CLE 82.5?±?13.0, CRE 152.3?±?24.4, ABE 90.6?±?18.0, LGE 95.4?±?10.5) and postprandial hyperinsulinaemia (mean ± SEM AUC [pmol/l?×?min]: chow 14.3?±?1.4, HFHS 31.4?±?3.1, BBE 27.2?±?4.0, CLE 17.7?±?2.2, CRE 32.6?±?6.3, ABE 22.7?±?18.0, LGE 23.9?±?2.5). None of the berry extracts affected C-peptide levels or body weight gain. Levels of hepatic serine phosphorylated Akt were 1.6-, 1.5- and 1.2-fold higher with CLE, ABE and LGE treatment, respectively, and hepatic carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-1 tyrosine phosphorylation was 0.6-, 0.7- and 0.9-fold increased in these mice vs vehicle-treated, HFHS-fed mice. These changes were associated with reduced liver triacylglycerol deposition, lower circulating endotoxins, alleviated hepatic and intestinal inflammation, and major gut microbial alterations (e.g. bloom of Akkermansia muciniphila, Turicibacter and Oscillibacter) in CLE-, ABE- and LGE-treated mice.
Our findings reveal novel mechanisms by which polyphenolic extracts from ABE, LGE and especially CLE target the gut-liver axis to protect diet-induced obese mice against metabolic endotoxaemia, insulin resistance and hepatic steatosis, which importantly improves hepatic insulin clearance. These results support the potential benefits of these Arctic berries and their integration into health programmes to help attenuate obesity-related chronic inflammation and metabolic disorders.
All raw sequences have been deposited in the public European Nucleotide Archive server under accession number PRJEB19783 ( https://www.ebi.ac.uk/ena/data/view/PRJEB19783 ).
Fatty liver disease (FLD) has been identified as constituting cardiometabolic risk. However, evidence on the association of fatty liver index (FLI) with cardiovascular disease (CVD) is largely cross-sectional, with limited evidence on the predictability of incident CVD, and specifically, acute myocardial infarction (AMI). Therefore, we aimed to investigate the prospective associations between fatty liver as estimated by FLI and incident CVD, and specifically AMI, in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort.
Our patients were 1205 middle-aged men free of CVD at baseline. The associations of baseline FLI with incident CVD and incident AMI were analyzed using multivariable-adjusted Cox regression models.
During a median follow-up of 17 years, a total of 690 incident cases of CVD and 269 cases of AMI were recorded through Finnish registries. For incident CVD, for the high (FLI=60) versus the low (=30) FLI category, the hazard ratio (HR) was 1.77 [95% confidence interval (CI): 1.46-2.14] in the minimally adjusted model. With increasing adjustment, the association was attenuated progressively. In the most adjusted model, the HR was 1.41 (95% CI: 1.10-1.79). For incident AMI, for the high FLI category, the HR was 1.65 (95% CI: 1.22-2.23) in the minimally adjusted model, but in most comprehensive models when we included metabolic factors, the HR was not significant (HR=1.136, 95% CI: 0.777-1.662).
FLI can predict incident CVD. However, the predictability of AMI using FLI is subject to interactions of metabolic factors. Individuals with FLI in the moderate to high category should be evaluated and monitored for subclinical or overt cardiovascular (including coronary) disease.