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.
Laparoscopic Roux-en-Y gastric bypass (RYGB) induces a more favorable metabolic profile than expected by weight loss alone. In this study, we investigated the effect of RYGB on serum bile acid levels and their relation to clinical outcomes.
We included 30 obese patients who underwent RYGB (BMI?=?46.1?±?5.9 kg/m(2)). Clinical measurements and laboratory determinations were performed before surgery and 1 year after surgery. Fasting serum bile acids were measured by an enzymatic method and individual bile acids were quantified by HLPC-tandem mass spectrometry. Indirect calorimetry was performed to measure the rates of energy expenditure and substrate oxidation.
Fasting total serum bile acid levels increased twofold after RYGB (pre, 3.68?±?2.03 vs. post, 7.06?±?9.65 µmol/l, +92 %, p?=?0.002). This increase in total bile acids was accompanied by a decrease in conjugated bile acids, which correlated with decreased glucose oxidation (r?=?0.571, p?=?0.002) and with increased lipid oxidation (r?=?-0.626, p?=?0.0004). The change in taurine-conjugated bile acids correlated with altered DIO2 mRNA expression in adipose tissue (r?=?-0.498, p?=?0.013) potentially linking bile acid conjugation to substrate oxidation through DIO2.
Fasting serum bile acid levels increase after RYGB. More specifically, changes in bile acid conjugation after RYGB associate with altered energy metabolism.
Epigenetic variation may contribute to the development of complex metabolic diseases such as type 2 diabetes (T2D). Hepatic insulin resistance is a hallmark of T2D. However, it remains unknown whether epigenetic alterations take place in the liver from diabetic subjects. Therefore, we investigated the genome-wide DNA methylation pattern in the liver from subjects with T2D and nondiabetic controls and related epigenetic alterations to gene expression and circulating folate levels.
Liver biopsies were obtained from 35 diabetic and 60 nondiabetic subjects, which are part of the Kuopio Obesity Surgery Study. The genome-wide DNA methylation pattern was analyzed in the liver using the HumanMethylation450 BeadChip. RNA expression was analyzed from a subset of subjects using the HumanHT-12 Expression BeadChip.
After correction for multiple testing, we identified 251 individual CpG sites that exhibit differential DNA methylation in liver obtained from T2D compared with nondiabetic subjects (Q
Non-alcoholic steatohepatitis (NASH) is associated with changes in fatty acid (FA) metabolism. However, specific changes in metabolism and hepatic mRNA expression related to NASH independent of simple steatosis, obesity and diet are unknown.
Liver histology, serum and liver FA composition and estimated enzyme activities based on the FA ratios in cholesteryl esters and triglycerides were assessed in 92 obese participants of the Kuopio Obesity Surgery Study (KOBS) divided to those with normal liver, steatosis or NASH (30 men and 62 women, age 46.8±9.5years (mean±SD), BMI 44.2±6.2kg/m(2)). Plasma FA composition was also investigated in the Metabolic Syndrome in Men (METSIM) Study (n=769), in which serum alanine aminotransferase (ALT) was used as a marker of liver disease.
Obese individuals with NASH had higher activity of estimated activities of delta-6 desaturase (D6D, p
Approximately one third of the Finnish adult population are affected with overweight-related non-alcoholic fatty liver disease (NAFLD). NAFLD can appear as a simple fat accumulation in the liver of the liver, but in some individuals the condition may advance to non-alcoholic steatohepatitis (NASH) and even to liver cirrhosis. In many cases, NAFLD is detected as an incidental finding. In differential diagnosis, the most common alternatives are alcohol use, drugs and viral hepatites. For a patient with NAFLD, the risk factors of cardiovascular diseases should be investigated and the possibility of having NASH and liver fibrosis assessed. Targeted therapy for NASH is not yet available.
Limited information exists on how the relationship between dietary intake of fat and fatty acids in erythrocytes and plasma is modulated by polymorphisms in the FADS gene cluster. We examined gene-diet interaction of total marine PUFA intake with a known gene encoding ?-5 desaturase enzyme (FADS1) variant (rs174550) for fatty acids in erythrocyte membranes and plasma phospholipids (PL), cholesteryl esters (CE), and triglycerides (TG).
In this cross-sectional study, fatty acid compositions were measured using GC, and total intake of polyunsaturated fat from fish and fish oil was estimated using a food frequency questionnaire in a subsample (n = 962) of the Metabolic Syndrome in Men Study. We found nominally significant gene-diet interactions for eicosapentaenoic acid (EPA, 20:5n-3) in erythrocytes (pinteraction = 0.032) and for EPA in plasma PL (pinteraction = 0.062), CE (pinteraction = 0.035), and TG (pinteraction = 0.035), as well as for docosapentaenoic acid (22:5n-3) in PL (pinteraction = 0.007). After excluding omega-3 supplement users, we found a significant gene-diet interaction for EPA in erythrocytes (pinteraction
Nonalcoholic steatohepatitis (NASH) is associated with increased synthesis of triglycerides and cholesterol coupled with increased VLDL synthesis in the liver. In addition, increased cholesterol content in the liver associates with NASH. Here we study the association of lipoprotein subclass metabolism with NASH. To this aim, liver biopsies from 116 morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, BMI 45.1 ± 6.1 kg/m², 39 men and 77 women] were used for histological assessment. Proton NMR spectroscopy was used to measure lipid concentrations of 14 lipoprotein subclasses in native serum samples at baseline and after obesity surgery. We observed that total lipid concentration of VLDL and LDL subclasses, but not HDL subclasses, associated with NASH [false discovery rate (FDR)
Cites: Nat Genet. 2008 Dec;40(12):1461-518820647
Cites: J Hepatol. 2009 Apr;50(4):789-9619231010
Cites: Analyst. 2009 Sep;134(9):1781-519684899
Cites: Hepatology. 2009 Sep;50(3):772-8019650159
Cites: Circulation. 2009 Oct 27;120(17):e149; author reply e15019858422
In animal experiments persistent organic pollutants (POPs) cause hepatosteatosis. In epidemiological studies POPs have positive associations with serum markers of nonalcoholic fatty liver disease (NAFLD) and together with obesity synergistic association with insulin resistance. Because insulin resistance and obesity are critical in NAFLD pathogenesis, we investigated the association of serum pollutant levels with liver histology and alanine aminotransferase (ALT) in morbidly obese.
Liver biopsies were from 161 participants of the Kuopio Obesity Surgery Study (KOBS) who underwent bariatric surgery 2005-2011. Liver histology was categorized as normal, steatosis and non-alcoholic steatohepatitis (NASH). Liver phenotype at baseline and ALT at baseline and 12 months post-surgery were correlated to serum POP concentrations at respective time points. As lipophilic POPs concentrate to smaller fat volume during weight loss, serum levels before and 12 months after bariatric surgery were compared.
Baseline serum concentration of PCB-118, ?-HCH and several PFAAs had an inverse association with lobular inflammation possibly due to changes in bile acid metabolism. ALT had negative associations with many POPs at baseline that turned positive at 12 months after major clinical improvements. There was an interaction between some POPs and sex at 12 months, and in stratified data positive associations were observed mainly in females but not in males.
We found a negative association between serum concentrations of PCB-118, ?-HCH and several PFAAs with lobular inflammation at baseline. Positive POPs-ATL associations at 12 months among women suggest that increased POP concentrations may decrease the degree of liver recovery.
Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology.
Clinical characteristics, PNPLA3 genotype at rs738409, and serum cytokeratin 18 fragments were measured in 296 consecutive bariatric surgery patients who underwent a liver biopsy to discover and validate a NASH score ('NASH score'). We also defined the cut-off for NASH for a previously validated NAFLD liver fat score to diagnose NASH in the same cohort ('NASH liver fat score'). Both scores were validated in an Italian cohort comprising of 380, mainly non-bariatric surgery patients, who had undergone a liver biopsy for NASH. The cut-offs were utilized in the Finnish population-based D2D-study involving 2849 subjects (age 45-74 years) to estimate the population prevalence of NASH.
The final 'NASH Score' model included PNPLA3 genotype, AST and fasting insulin. It predicted NASH with an AUROC 0.774 (0.709, 0.839) in Finns and 0.759 (0.711, 0.807) in Italians (NS). The AUROCs for 'NASH liver fat score' were 0.734 (0.664, 0.805) and 0.737 (0.687, 0.787), respectively. Using 'NASH liver fat score' and 'NASH Score', the prevalences of NASH in the D2D study were 4.2% (95% CI: 3.4, 5.0) and 6.0% (5.0, 6.9%). Sensitivity analysis was performed by taking into account stochastic false-positivity and false-negativity rates in a Bayesian model. This analysis yielded population prevalences of NASH of 3.1% (95% stimulation limits 0.2-6.8%) using 'NASH liver fat score' and 3.6% (0.2-7.7%) using 'NASH Score'.
The population prevalence of NASH in 45-74 year old Finnish subjects is ~ 5%.