Serum lipids are associated with nonalcoholic fatty liver disease: a pilot case-control study in Mexico
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Blood
DISEASE(S): Fatty Liver Disease
PROVIDER: ST002091 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and cirrhosis. NAFLD is mediated by changes in lipid metabolism and known risk factors include obesity, metabolic syndrome, and diabetes. The aim of this study was to better understand differences in the lipid composition of individuals with NAFLD compared to controls, by performing direct infusion lipidomics on serum biospecimens from a cohort study of adults in Mexico.MethodsA nested case-control study was conducted with a sample of 98 NAFLD cases and 100 healthy controls who are participating in an on-going, longitudinal study in Mexico. NAFLD cases were clinically confirmed using elevated liver enzyme tests and liver ultrasound or liver ultrasound elastography, after excluding alcohol abuse, and 100 controls were identified as having at least two consecutive normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (< 40 U/L) results in a 6-month period, and a normal liver ultrasound elastography result in January 2018. Samples were analyzed on the Sciex Lipidyzer Platform and quantified with normalization to serum volume. As many as 1100 lipid species can be identified using the Lipidyzer targeted multiple-reaction monitoring list. The association between serum lipids and NAFLD was investigated using analysis of covariance, random forest analysis, and by generating receiver operator characteristic (ROC) curves.ResultsNAFLD cases had differences in total amounts of serum cholesterol esters, lysophosphatidylcholines, sphingomyelins, and triacylglycerols (TAGs), however, other lipid subclasses were similar to controls. Analysis of individual TAG species revealed increased incorporation of saturated fatty acyl tails in serum of NAFLD cases. After adjusting for age, sex, body mass index, and PNPLA3 genotype, a combined panel of ten lipids predicted case or control status better than an area under the ROC curve of 0.83.ConclusionsThese preliminary results indicate that the serum lipidome differs in patients with NAFLD, compared to healthy controls, and suggest that assessing the desaturation state of TAGs or a specific lipid panel may be useful clinical tools for the diagnosis of NAFLD.
| S-EPMC8504048 | biostudies-literature
Project description: Not available
| S-EPMC11022063 | biostudies-literature
Project description:BackgroundPolymorphisms have been identified to predispose to NAFLD. Here, we accessed the seven polymorphisms of rs1260326, rs780094 in GCKR, rs2954021 near TRIB1, rs2228603 in NCAN, rs58542926 in TM6SF2, rs12137855 near LYPLAL1, and rs10883437 near CPN1 on NAFLD susceptibility in the Uygur population.Material and methodsWe collected 620 samples (317 NAFLD and 303 controls) for this case-control study. Meta-analysis was performed using Stata Software.ResultsOur data detected that the rs1260326 (T vs. C: OR = 1.27, 95% CI = 1.01-1.59) and rs780094 (T vs. C: OR = 1.30, 95% CI = 1.04-1.63) were significantly associated with the susceptibility to NAFLD in Uygur population. The rs1260326 and rs780094 T/T genotype are significantly associated with soda, egg, and soybean intakes in the consumption group with twice or more in a week. Furthermore, a significant haplotype effect of rs1260326/T- rs780094/T was found (OR = 1.29, 95% CI: 1.03-1.62) compared with CC haplotype. An additional meta-analysis using 4352 cases and 10,168 controls established that rs780094 (OR = 1.21, 95%CI: 1.14-1.28) is significantly associated with NAFLD. Finally, among the 4 case-control studies on rs1260326, including 712 NAFLD and 658 controls, significant associations were found in Asian, liver biopsy, adult and pediatric groups.ConclusionCollectively, both our case-control study and meta-analysis confirm a significant association between rs780094 and NAFLD. Additionally, our results suggest Asian-specific, liver biopsy-specific, adult-specific and pediatric-specific associations between the rs1260326 and NAFLD. Moreover, the rs1260326 and rs780094 T/T genotype are significantly associated with food habits, such as soda, egg, and soybean.
| S-EPMC6334439 | biostudies-literature
Project description:BackgroundWhile aerobic training is generally recommended as therapeutic exercise in guidelines, the effectiveness of resistance training has recently been reported in the management of nonalcoholic fatty liver disease (NAFLD). Acceleration training (AT) is a new training method that provides a physical stimulation effect on skeletal muscles by increasing gravitational acceleration with vibration. AT has recently been indicated as a component of medicine. In this study, we evaluated the effectiveness of AT in the management of NAFLD in obese subjects.MethodsA total of 18 obese patients with NAFLD who had no improvement in liver function test abnormalities and/or steatosis grade after 12 weeks of lifestyle counseling were enrolled in an AT program. These patients attended a 20-minute session of AT twice a week for 12 consecutive weeks.ResultsDuring the AT program, the NAFLD patients showed a modest increase in the strength (+12.6%) and cross-sectional area (+3.1%) of the quadriceps, coupled with a significant reduction in intramyocellular lipids (-26.4%). Notably, they showed a modest reduction in body weight (-1.9%), abdominal visceral fat area (-3.4%), and hepatic fat content (-8.7%), coupled with a significant reduction in levels of aminotransferase (-15.7%), γ-glutamyltransferase (-14.4%), leptin (-9.7%), interleukin-6 (-26.8%), and tumor necrosis factor-α (-17.9%), and a significant increase of adiponectin (+8.7%). On a health-related quality of life survey, the patients showed an improvement in physical functioning (+17.3%), physical role (+9.7%), general health (+22.1), and social functioning (+6.0%).ConclusionAT reduced hepatic and intramyocellular fat contents and ameliorated liver function test abnormalities in obese patients with NAFLD, which was coupled with improved physical function and body adiposity. AT is clinically beneficial for the management of NAFLD.
| S-EPMC4230176 | biostudies-literature
Project description:Spontaneous insulin resistance and NAFLD emerged in AxB F1 male mice with parent-of-origin effects such that AB6F1 (AJ dam x B6 sire) were susceptible whereas B6AF1 (B6 dam x AJ sire) were resistant. We used microarrays to correlate gene expression with the NAFLD phenotype in 9-month-old male AB6F1 (affected) versus B6AF1 (unaffected) mice. Whole liver slices from two 9-month-old AB6F1 and B6AF1 males were collected for RNA extraction and hybridization on Affymetrix microarrays.
2011-01-05 | E-GEOD-26225 | biostudies-arrayexpress
Project description:BackgroundRecently genome-wide association studies identified that NCAN rs2228603 polymorphism was associated with non-alcoholic fatty liver disease (NAFLD) mainly in subjects of European ancestry. While no research have been conducted to demonstrate the relationship between NCAN rs2228603 and NAFLD in Chinese Han adults. The aim of this study was to investigate whether NCAN rs2228603 is associated with NAFLD in Chinese population.MethodsGene NCAN rs2228603 was genotyped in 182 patients with NAFLD and 195 healthy controls. The expression of NCAN was tested according to polymerase chain reaction analysis (PCR) and serum lipids were performed by biology techniques.ResultsNo significant difference was found in genotype and allele frequencies of NCAN rs2228603 between the NAFLD group and the controls (P > 0.05). Subjects with the NCAN rs2228603 CT genotype showed a higher level of alkaline phosphatase (AKP) (P = 0.017) and a higher high-density lipoprotein (HDL) (P < 0.05).ConclusionsOur study for the first time identified that the gene NCAN rs2228603 is not a risk factor for the incidence of NAFLD in Chinese population. Also we found the dual and opposite role of T variant in protecting liver with a higher level of HDL and conferring risk for liver damage with a higher level of AKP.Trial registrationChinese Clinical Trial Register.gov Identifier: ChiCTR-ROC-15006447 .
| S-EPMC5124242 | biostudies-literature
Project description:Obesity leads to fat infiltration of multiple organs including the heart, kidneys, and liver. Under conditions of oxidative stress, fat-derived cytokines are released locally and result in an inflammatory process and organ dysfunction. In the liver, fat infiltration has been termed nonalcoholic fatty liver disease, which may lead to nonalcoholic steatohepatitis. No data are available, however, on the influence of obesity on pancreatic fat and cytokines, and nonalcoholic fatty pancreas disease (NAFPD) has not been described. Therefore, we designed a study to determine whether obesity is associated with increased pancreatic fat and cytokines.Thirty C57BL/6J lean control and 30 leptin-deficient obese female mice were fed a 15% fat diet for 4 weeks. At 12 weeks of age all animals underwent total pancreatectomy. Pancreata from each strain were pooled for measurement of a) wet and dry weight, b) histologic presence of fat, c) triglycerides, free fatty acids (FFAs), cholesterol, phospholipids, and total fat, and d) interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha). Data were analyzed by Student's t test and Fisher's exact test.Pancreata from obese mice were heavier (p<0.05) and had more fat histologically (p<0.05). Pancreata from obese mice had more triglycerides, FFAs, cholesterol, and total fat (p<0.05). Triglycerides represented 11% of pancreatic fat in lean mice compared with 67% of pancreatic fat in obese mice (p<0.01). Cytokines IL-1beta and TNF-alpha also were elevated in the pancreata of obese mice (p<0.05).These data suggest that obese mice have 1) heavier pancreata, 2) more pancreatic fat, especially triglycerides and FFAs, and 3) increased cytokines. We conclude that obesity leads to nonalcoholic fatty pancreatic disease.
| S-EPMC2215403 | biostudies-other
Project description:Acetate, propionate and butyrate are the main short-chain fatty acids (SCFAs) that arise from the fermentation of fibers by the colonic microbiota. While many studies focus on the regulatory role of SCFAs, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. To investigate this aspect, we infused conscious mice with physiological quantities of stable isotopes [1-13C]acetate, [2-13C]propionate or [2,4-13C2]butyrate directly into the cecum, which is the natural production site in mice, and analyzed their interconversion by the microbiota as well as their metabolism by the host. Cecal interconversion - pointing to microbial cross-feeding - was high between acetate and butyrate, low between butyrate and propionate and almost absent between acetate and propionate. As much as 62% of infused propionate was used in whole-body glucose production, in line with its role as gluconeogenic substrate. Conversely, glucose synthesis from propionate accounted for 69% of total glucose production. The synthesis of palmitate and cholesterol in the liver was high from cecal acetate (2.8% and 0.7%, respectively) and butyrate (2.7% and 0.9%, respectively) as substrates, but low or absent from propionate (0.6% and 0.0%, respectively). Label incorporation due to chain elongation of stearate was approximately 8-fold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert only a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6h infusion period. Altogether, gut-derived acetate, propionate and butyrate play important roles as substrates for glucose, cholesterol and lipid metabolism. Mice were infused in cecum with stably-labelled isotopes of the three main short chain fatty acids or control solution. After 6 hrs, livers were removed and pooled RNA samples were subjected to gene expression profiling.
2013-10-21 | E-GEOD-45926 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-08-30 | E-GEOD-31803 | biostudies-arrayexpress
Project description:Nonalcoholic fatty liver disease represents a spectrum of pathology that ranges from benign steatosis to potentially-progressive steatohepatitis and affects more than 30% of US adults. Advanced NAFLD is associated with increased morbidity and mortality from cirrhosis, primary liver cancer, cardiovascular disease and extrahepatic cancers. Accurate identification of patients at risk for advanced NAFLD is challenging. The aims of this study were to define the liver gene expression patterns that distinguish mild from advanced NAFLD and to develop a gene expression profile associated with advanced NAFLD. We analyzed total RNA from 72 patients with NAFLD (40 with mild NAFLD, fibrosis stage 0-1 and 32 with advanced NAFLD, fibrosis stage 3-4) and developed a gene profile associated with advanced NAFLD. This dataset is part of the TransQST collection.
2013-08-30 | E-GEOD-49541 | biostudies-arrayexpress