INTRODUCTION: The study of single nucleotide polymorphisms (SNPs) of the leptin receptor gene (LEPR) based on next generation genomic sequencing (NGS) data is becoming an increasingly important aspect of diagnosis, treatment and prevention of both metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) phenotypes. MATERIAL AND METHODS: 35 obese children 6-18 years old were examined by the NGS method with bioinformatic analysis. The main group (n = 18) was formed by children with MUO, according to the recommendations of the expert group of the National Heart, Lung, and Blood Institute. The control group (n = 17) was represented by children with MHO. Statistical methods were used: analysis of variance, Wald's sequential analysis, Spearman's correlation analysis, analysis of nominal data and multiple discriminant analysis. RESULTS: 10 types of non-synonymous SNPs (rs3790435, rs1137100, rs2186248, rs70940803, rs79639154, rs1359482195, rs1137101, rs1805094, rs13306520, rs13306522) of the LEPR gene in obese children have been identified. Multiple discriminant analysis demonstrated that the following LEPR SNPs are of greatest importance in the development of MUO: rs3790435, rs13306522, rs13306520. Analysis of nominal data revealed significant differences in the groups for Copy number variation (CNV) rs3790435 of the LEPR gene. Wald's analysis allowed us to identify 6 important predictors of MUO (І ≥ 0.5): 2 CNV rs3790435 (Relative Risk, RR = 2, Prognostic coefficient, PC = +2.76); male gender of the child (RR = 1.3, PC = +1.35); rs3790435 (RR = 1.9, PC = +2.76); hyperleptinemia more than 40.56 ng/ml (RR = 2, PC = +3); CNV rs1359482195 ≥ 3 (RR = 1.9, PC = +5.8); SNP of the LEPR gene ≥4 (RR = 3.8, PC = +5.8). CONCLUSION: Children with the genotype rs3790435 gene LEPR had signs of MUO more often.
- MeSH
- dítě MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus MeSH
- leptin genetika MeSH
- leptinové receptory * genetika MeSH
- lidé MeSH
- mladiství MeSH
- obezita dětí a dospívajících * genetika MeSH
- variabilita počtu kopií segmentů DNA MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
In mammals, leptin and tumor-necrosis factor (TNF) are prominent interacting adipokines mediating appetite control and insulin sensitivity. While TNF pleiotropically functions in immune defense and cell survival, leptin is largely confined to signaling energy stores in adipocytes. Knowledge about the function of avian leptin and TNF is limited and they are absent or lowly expressed in adipose, respectively. Employing radiation-hybrid mapping and FISH-TSA, we mapped TNF and its syntenic genes to chicken chromosome 16 within the major histocompatibility complex (MHC) region. This mapping position suggests that avian TNF has a role in regulating immune response. To test its possible interaction with leptin within the immune system and beyond, we compared the transcription patterns of TNF, leptin and their cognate receptors obtained by meta-analysis of GenBank RNA-seq data. While expression of leptin and its receptor (LEPR) were detected in the brain and digestive tract, TNF and its receptor mRNAs were primarily found in viral-infected and LPS-treated leukocytes. We confirmed leptin expression in the duodenum by immunohistochemistry staining. Altogether, we suggest that whereas leptin and TNF interact as adipokines in mammals, in birds, they have distinct roles. Thus, the interaction between leptin and TNF may be unique to mammals.
- MeSH
- buněčné linie MeSH
- duodenum metabolismus MeSH
- kur domácí genetika metabolismus MeSH
- leptin genetika metabolismus MeSH
- leptinové receptory metabolismus MeSH
- mapování chromozomů * MeSH
- mapování pomocí radiačních hybridů MeSH
- messenger RNA genetika metabolismus MeSH
- metafáze genetika MeSH
- receptory TNF genetika metabolismus MeSH
- regulace genové exprese * MeSH
- savci genetika MeSH
- signální transdukce * MeSH
- syntenie genetika MeSH
- TNF-alfa genetika metabolismus MeSH
- trávení * MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Molecular pathogenesis of Down syndrome (DS) is still incompletely understood. Epigenetic mechanisms, including miRNAs gene expression regulation, belong to potential influencing factors. The aims of this study were to compare miRNAs expressions in placentas with normal and trisomic karyotype and to associate differentially expressed miRNAs with concrete biological pathways. METHODS: A total of 80 CVS samples - 41 with trisomy 21 and 39 with normal karyotype - were included in our study. Results obtained in the pilot study using real-time PCR technology and TaqMan Human miRNA Array Cards were subsequently validated on different samples using individual TaqMan miRNA Assays. RESULTS: Seven miRNAs were verified as upregulated in DS placentas (miR-99a, miR-542-5p, miR-10b, miR-125b, miR-615, let-7c and miR-654); three of these miRNAs are located on chromosome 21 (miR-99a, miR-125b and let-7c). Many essential biological processes, transcriptional regulation or apoptosis, were identified as being potentially influenced by altered miRNA levels. Moreover, miRNAs overexpressed in DS placenta apparently regulate genes involved in placenta development (GJA1, CDH11, EGF, ERVW-1, ERVFRD-1, LEP or INHA). CONCLUSION: These findings suggest the possible participation of miRNAs in Down syndrome impaired placentation and connected pregnancy pathologies. © 2016 John Wiley & Sons, Ltd.
- MeSH
- dospělí MeSH
- Downův syndrom genetika metabolismus MeSH
- epidermální růstový faktor genetika MeSH
- epigeneze genetická MeSH
- genové produkty env genetika MeSH
- inhibiny genetika MeSH
- kadheriny genetika MeSH
- konexin 43 genetika MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- leptin genetika MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- odběr choriových klků MeSH
- pilotní projekty MeSH
- placenta metabolismus MeSH
- placentace genetika MeSH
- studie případů a kontrol MeSH
- těhotenské proteiny genetika MeSH
- těhotenství MeSH
- transkriptom MeSH
- upregulace MeSH
- vývojová regulace genové exprese genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The aim of the study was to develop a diet which causes stable hyperglycaemia and development of diabetes in female Zucker diabetic fatty (ZDF) rats. We also examined whether worsened wound healing is caused only by hyperglycaemia or whether it is caused by more factors. Four types of special diets with a different content of fat were fed to eight groups of 3–7 (fa/fa or fa/+) rats. The following diets were used: H1 (24.6% fat), H2 (33.2%), C13004 (25.6%), and St1 (3.4%). We detected significant diet-dependent changes of weight and concentration of glucose in animals with leptin mutation (fa/fa). All examined indicators were significantly (P < 0.001) higher in (fa/fa) animals compared to the fa/+ ones no matter what diet they ate. All diets with high-fat content caused increased glycaemia, but only the diet with 24.6% fat caused a significant (P < 0.01) increase of glycaemia. Our results have proved that this diet is the most suitable to invoke and keep hyperglycaemia. The diet with 25.6% fat is suitable to invoke stable slightly increased glycaemia (10 mmol/l) and hyperinsulinaemia. On the other hand, the diet with 33.2% fat is unsuitable. We did not observe a significant influence of diet on wound healing. We developed a new diet more suitable for induction of stable hyperglycaemia in female ZDF rats than commercially available mixtures. Our study is the first to present recommendations for adjusting a high-fat diet to produce stable hyperglycaemia and hyperinsulinaemia in the rat model.
- MeSH
- diabetes mellitus MeSH
- dieta * klasifikace MeSH
- dietní tuky * MeSH
- hmotnostní přírůstek MeSH
- hojení ran MeSH
- hyperglykemie * MeSH
- inzulin krev MeSH
- krevní glukóza * MeSH
- krysa rodu rattus MeSH
- leptin genetika MeSH
- matrixová metaloproteinasa 3 genetika MeSH
- modely nemocí na zvířatech MeSH
- mutace MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Mutations in genes involved in energy balance regulation within the central nervous system lead to monogenic forms of obesities. Individuals with these mutations are characterized by early-onset obesity and in some cases by endocrine abnormalities. Carriers of leptin gene mutations are able to normalize their body weight after daily subcutaneous leptin administration. Pharmacotherapy targeting the specific-gene deficiencies has not clinically been tested in other monogenic obesities. Mutations in the melanocortin 4 receptor gene (MC4R) represent the most common monogenic cause of human obesity. Several treatment options have been investigated in subjects with MC4R mutations. Few studies showed that an intensive life-style intervention induces similar weight reduction in MC4R mutation carriers in comparison to MC4R mutation noncarriers. However, long-term body weight maintenance is hardly ever achieved in MC4R mutation carriers. Sibutramine, serotonin and noradrenalin reuptake inhibitor, in MC4R mutation carriers induced weight reduction and improved cardiometabolic health risks. This result was also found in our homozygous MC4R mutation carrier. In vitro studies of melanocortin agonists efficiently activate mutated MC4R with impaired endogenous agonist functional response and thus, further research in the development of drugs for MC4R mutations is needed. An administration of intranasal adrenocorticotropic hormone was not shown to be effective in subjects with pro-opiomelanocortin gene mutations. Bariatric surgery has also been performed in few of MC4R mutation carriers. After gastric banding, lower body weight reduction and worse improvement of metabolic complications was found in MC4R mutation carriers versus noncarriers. However, preliminary results suggest that diversionary operations as gastric bypass represent a suitable method also for MC4R mutation carriers. In conclusion, the management of monogenic obesities still remains a challenge.
- MeSH
- bariatrická chirurgie MeSH
- cyklobutany terapeutické užití MeSH
- dítě MeSH
- energetický metabolismus genetika MeSH
- heterozygot MeSH
- hmotnostní úbytek genetika MeSH
- homozygot MeSH
- index tělesné hmotnosti MeSH
- leptin genetika metabolismus MeSH
- lidé MeSH
- mutace MeSH
- obezita genetika terapie MeSH
- pro-opiomelanokortin agonisté genetika metabolismus MeSH
- receptor melanokortinový typ 4 genetika metabolismus MeSH
- tělesná hmotnost MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Nedávný výzkum ukázal, že leptin hraje integrální roli v normální fyziologii reprodukčního systému s komplexními interakcemi na všech úrovních hypotalamo-hypofyzárně-gonadální osy. Observační studie ukázaly, že stavy spojené s nadbytkem, deficitem nebo rezistencí na leptin mohou být spojovány s abnormálními reprodukčními funkcemi. Očekávají se další intervenční studie, zahrnující podávání leptinu, které by mohly objasnit komplexnost těchto vztahů a potenciálně poskytnout nové a lepší strategie pro řešení těchto klinických syndromů. Klíčová slova: leptin, reprodukce, hypotalamo-hypofyzárně-gonadální osa.
Leptin may act as the critical link between adipose tissue and the reproductive systém, indicating whather adequate energy reserves are presenting for normal reproductive functions. Future interventional studies involving leptin administration are excepted to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunctions associated with states of relative leptin deficiency or resistence. Key words: leptin, reproduction, hypothalamic-pituitary-gonadal axis.
- MeSH
- anamnéza MeSH
- Bardetův-Biedlův syndrom MeSH
- diabetes mellitus 2. typu MeSH
- diagnostické techniky a postupy MeSH
- dítě MeSH
- genetická predispozice k nemoci MeSH
- index tělesné hmotnosti MeSH
- jídelníček MeSH
- kardiovaskulární nemoci MeSH
- látky proti obezitě farmakologie klasifikace MeSH
- leptin genetika MeSH
- lidé MeSH
- mladiství MeSH
- mutace MeSH
- nadváha * epidemiologie etiologie genetika komplikace patologie terapie MeSH
- nemoci endokrinního systému MeSH
- obezita * epidemiologie etiologie genetika komplikace patologie terapie MeSH
- Praderův-Williho syndrom MeSH
- předškolní dítě MeSH
- prevalence MeSH
- receptor melanokortinový typ 4 genetika MeSH
- riziko MeSH
- statistika jako téma MeSH
- stravovací zvyklosti MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- MeSH
- atopická dermatitida diagnóza genetika MeSH
- autoimunitní nemoci diagnóza genetika MeSH
- diabetes mellitus 1. typu genetika MeSH
- diabetes mellitus 2. typu diagnóza genetika MeSH
- dyslipidemie diagnóza farmakoterapie genetika MeSH
- genetická predispozice k nemoci epidemiologie genetika MeSH
- hyperhomocysteinemie diagnóza genetika MeSH
- hypertenze diagnóza genetika MeSH
- kardiomyopatie diagnóza genetika MeSH
- krevní nemoci diagnóza genetika MeSH
- leptin genetika metabolismus MeSH
- lidé MeSH
- nádory diagnóza genetika MeSH
- neurodegenerativní nemoci diagnóza genetika MeSH
- obezita diagnóza genetika MeSH
- primární prevence metody MeSH
- primární zdravotní péče MeSH
- puriny metabolismus MeSH
- rizikové faktory MeSH
- Check Tag
- lidé 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 genetika krev MeSH
- běloši genetika MeSH
- dospělí MeSH
- energetický příjem MeSH
- genotyp MeSH
- hubenost genetika krev MeSH
- interleukin-6 genetika MeSH
- jednonukleotidový polymorfismus MeSH
- leptin genetika krev MeSH
- leptinové receptory genetika krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- morbidní obezita genetika krev MeSH
- obezita genetika krev 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
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Adipose tissue is an important target for thyroid hormones (TH). However, the metabolism of TH in white adipose tissue is poorly characterized. Our objective was to describe possible changes in activities of TH-metabolizing enzymes in white adipose tissue, and the role of TH metabolism in the tissue during obesogenic treatment, caloric restriction and in response to leptin in mice. Activity of type I iodothyronine 5’-deiodinase (D1) in white fat was stimulated by a high-fat diet, which also increased plasma leptin levels, while brown adipose tissue D1 activity did not change. Caloric restriction decreased the activity of D1 in white fat (but not in the liver), reduced leptin levels, and increased the expression of stearoyl CoA desaturase 1 (SCD-1), a marker and mediator of the effect of leptin on tissue metabolism. Leptin injections increased D1 activity and down-regulated SCD-1 in white fat. Our results demonstrate changes in D1 activity in white adipose tissue under the conditions of changing adiposity, and a stimulatory effect of leptin on D1 activity in the tissue. These results suggest a functional role for D1 in white adipose tissue, with D1 possibly being involved in the control of adipose tissue metabolism and/or accumulation of the tissue.
- MeSH
- bílá tuková tkáň enzymologie patofyziologie MeSH
- financování organizované MeSH
- fyziologie výživy zvířat MeSH
- hnědá tuková tkáň enzymologie patofyziologie MeSH
- hormony štítné žlázy metabolismus MeSH
- injekce subkutánní MeSH
- jodidperoxidasa genetika metabolismus MeSH
- kalorická restrikce MeSH
- leptin aplikace a dávkování genetika metabolismus MeSH
- messenger RNA metabolismus MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- obezita enzymologie patofyziologie MeSH
- regulace genové exprese enzymů MeSH
- rekombinantní proteiny metabolismus MeSH
- stearyl-CoA-desaturasa genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH