BACKGROUND: Although metabolic associate fatty liver disease (MAFLD) is associated with obesity, it can also occur in lean patients. MAFLD is more aggressive in lean patients compared to obese patients, with a higher risk of mortality. Specific biomarkers to diagnose differentially lean or overweight MAFLD are missing. Histones and nucleosomes are released in the bloodstream upon cell death. Here, we propose a new, fast, imaging and epigenetics based approach to investigate the severity of steatosis in lean MAFLD patients. RESULTS: A total of 53 non-obese patients with histologically confirmed diagnosis of MAFLD were recruited. Twenty patients displayed steatosis grade 1 (0-33%), 24 patients with steatosis grade 2 (34-66%) and 9 patients with steatosis grade 3 (67-100%). The levels of circulating nucleosomes were assayed using enzyme-linked immunosorbent assay, while individual histones or histone dimers were assayed in serum samples by means of a new advanced flow cytometry ImageStream(X)-adapted method. Circulating nucleosome levels associated poorly with MAFLD in the absence of obesity. We implemented successfully a multi-channel flow methodology on ImageStream(X), to image single histone staining (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2). We report here a significant depletion of the levels of histone variants macroH2A1.1 and macroH2A1.2 in the serum of lean MAFLD patients, either individually or in complex with H2B. CONCLUSIONS: In summary, we identified a new circulating histone signature able to discriminate the severity of steatosis in individuals with lean MAFLD, using a rapid and non-invasive ImageStream(X)-based imaging technology.

• Klíčová slova
• Epigenetics, Histones, ImageStream, Lean MAFLD, Liquid biopsy, Metabolic health,
• MeSH
• dospělí MeSH
• histony krev   MeSH
• hubenost krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolické nemoci krev   komplikace   MeSH
• stupeň závažnosti nemoci MeSH
• ztučnělá játra krev   komplikace   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histony MeSH

First intron variability of the fat mass and obesity associated gene (FTO) has strong impact on adiposity. We focused on lean women carrying the most "obesity-risk" haplotype to study their anthropometric parameters and hormonal and metabolic profile. Genotype-phenotype correlation was performed in a group of 172 lean women (body mass index (BMI) >/=18.5 and 25 kg/m(2); age 26.8+/-7.26 years), 77 of them used hormonal contraceptives. Even in lean women the association of the risk haplotype CAGA with BMI was confirmed but it did not influence the anthropometric indices of body composition. CAGA carriers compared to non-carriers had significantly higher both fasting (p=0.016) and post glucose load (p<0.001) levels of growth hormone (GH), significantly higher glucose, insulin and C-peptide levels in the late phase of oGTT and lower fasting concentration of total cholesterol and LDL-cholesterol. Administration of hormonal contraceptives further increased observed hormonal and metabolic effects in CAGA carriers. We conclude that higher levels of GH in lean women carrying the FTO "obesity risk" haplotype could protect them from the development of obesity. The relation between the FTO gene variability and GH secretion has to be elucidated. This is the first study demonstrating the interaction of FTO genotype with hormonal contraception.

• MeSH
• adipozita fyziologie   MeSH
• dospělí MeSH
• gen pro FTO MeSH
• genetická variace genetika   MeSH
• glukosa metabolismus   MeSH
• hubenost krev   diagnóza   genetika   MeSH
• index tělesné hmotnosti MeSH
• kohortové studie MeSH
• lidé MeSH
• lidský růstový hormon krev   MeSH
• metabolismus lipidů fyziologie   MeSH
• mladý dospělý MeSH
• obezita krev   genetika   MeSH
• proteiny genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• FTO protein, human MeSH Prohlížeč
• gen pro FTO MeSH
• glukosa MeSH
• lidský růstový hormon MeSH
• proteiny MeSH

Personal food preferences can either enhance or suppress the development of obesity and the selection and proportion of macronutrients in the diet seem to have a heritable component. In the present study, we therefore focused on dietary composition as a specific trait related to obesity and we determined whether genetic variations in leptin (LEP), LEP receptor (LEPR), adiponectin (ADIPOQ), IL-6 and pro-opiomelanocortin (POMC) underlie specific native food preferences and obesity-related anthropometric parameters. The total of 409 individuals of Czech Caucasian origin were enrolled into the present study and 7 d food records were obtained from the study subjects along with selected anthropometric measurements. In a subset of study subjects, plasma levels of ADIPOQ, LEP and soluble LEPR were measured. Independently of the BMI of the individuals, common variations in LEP and LEPR genes were associated with specific eating patterns, mainly with respect to timing of eating. The LEP + 19A/G polymorphism served as an independent predictor for BMI, percentage of body fat and skinfold thickness and significantly affected the time structure of the daily energy intake. The POMC RsaI polymorphism was associated with percentage of body fat. The ADIPOQ 45 T/G polymorphism was associated with the thickness of the subscapular skinfold. The LEPR Gln223Arg polymorphism was associated with multiple parameters, including diastolic blood pressure, meal sizes during the day and plasma ADIPOQ levels. In a separate analysis, soluble leptin receptor (sObR) plasma levels and LEP:sObR ratio were significantly correlated with systolic blood pressure (beta = - 0.66, P = 0.002; beta = - 1.23, P = 0.02) and sObR plasma levels also served as an independent predictor for diastolic blood pressure (beta = - 0.50; P = 0.04). To conclude, we report common allelic variants associated with specific feeding behaviour and obesity-related anthropometric traits. Moreover, we identified allelic variants that significantly influence the time structure of food intake during the day.

• MeSH
• adiponektin krev   genetika   MeSH
• běloši genetika   MeSH
• dospělí MeSH
• energetický příjem * MeSH
• genotyp * MeSH
• hubenost krev   genetika   MeSH
• interleukin-6 genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• leptin krev   genetika   MeSH
• leptinové receptory krev   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• morbidní obezita krev   genetika   MeSH
• obezita krev   genetika   MeSH
• polymorfismus genetický * MeSH
• preference v jídle * MeSH
• pro-opiomelanokortin genetika   MeSH
• referenční hodnoty MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• adiponektin MeSH
• interleukin-6 MeSH
• leptin MeSH
• leptinové receptory MeSH
• pro-opiomelanokortin MeSH