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3.
Orv Hetil ; 160(35): 1387-1394, 2019 Sep.
Artigo em Húngaro | MEDLINE | ID: mdl-31448645

RESUMO

Introduction and aim: In case of imaging modalities using ionizing radiation, radiation exposure of the patients is a vital issue. It is important to survey the various dose-reducing techniques to achieve optimal radiation protection while keeping image quality on an optimal level. Method: We reprocessed 105 patients' data prospectively between February and April 2017. The determination of the radiation dose was based on the effective dose, calculated by multiplying the dose-length product (DLP) and dose-conversation coefficient. In case of image quality we used signal-to-noise ratio (SNR) based on manual segmentation of region of interest (ROI). For statistical analysis, one sample t-test and Wilcoxon signed rank test were used. Results: Using iterative reconstruction, the effective dose was significantly lower (p<0.001) in both native and contrast-enhanced abdominal, contrast-enhanced chest CT scans and in the case of the total effective dose. At native and contrast-enhanced abdominal CT scans, the noise content of the images showed significantly lower (p<0.001) values for iterative reconstruction images. At contrast-enhanced chest CT scans there was no significant difference between the noise content of the images (p>0.05). Conclusion: Using iterative reconstruction, it was possible to achieve significant dose reduction. Since the noise content of the images was not significantly higher using the iterative reconstruction compared to the filtered back projection, further dose reduction can be achievable while preserving the optimal quality of the images. Orv Hetil. 2019; 160(35): 1387-1394.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31361301

RESUMO

CONTEXT: Despite the emerging evidence on the role of oxytocin (OXT) in metabolic diseases, there is a lack of well powered studies addressing the relationship of circulating OXT with obesity and diabetes. OBJECTIVES AND DESIGN: Here, we measured OXT in a study cohort (n=721; 396 women, 325 men; mean age±SD - 47.7±15.2 years) with sub-phenotypes related to obesity including anthropometric traits such as body mass index (BMI; mean±SD - 47.7±15.2 kg/m2), waist-to-hip-ratio (WHR; 0.88±0.09), blood parameters (glucose - 5.32±0.50 mmol/l, insulin - 5.3±3.3 µU/ml, lipids) and oral glucose tolerance test (OGTT) to clarify the association with OXT. We also tested in a genome-wide association study (GWAS) whether the inter-individual variation in OXT serum levels might be explained by genetic variation. RESULTS: The OXT concentration was increased in subjects with elevated BMI and positively correlated with WHR, waist circumference and triglyceride levels. The OXT concentration in subjects with BMI<25 kg/m2 was significantly lower (n=256; 78.6 pg/ml) than in subjects with a BMI between 25-30 kg/m2 (n=314; 98.5 pg/ml, p=6x10-6) and with BMI>30 kg/m2 (n=137; 106.4 pg/ml, p=8x10-6). OXT levels were also positively correlated with plasma glucose and insulin and were elevated in subjects with impaired glucose tolerance (p=4.6x10-3). Heritability of OXT was estimated to 12.8%. In a GWAS, two hits in linkage disequilibrium close (19kb) to the OXT reached genome-wide significant association (top-hit rs12625893, p=3.1x10-8, explained variance 3%). CONCLUSIONS: Our data show that OXT is genetically affected by a variant in OXT and is associated with obesity and impaired glucose tolerance.

5.
Magy Onkol ; 63(2): 116-124, 2019 06 21.
Artigo em Húngaro | MEDLINE | ID: mdl-31225535

RESUMO

Our aim was to present our treatment and verification protocols of linear accelerator-based lung and abdominal stereotactic ablative radiotherapy (SABR). During our treatments both the volumetric imaging (3D/4D CBCT/CT) and triggered kV intrafractional tumor motion control could be combined allowing a full control on the whole workflow. The most optimal kV directions from which the tumor is well detectable were defined. Tumor movements measured on cine MRI in treatment position correlated well with the ones on 4D CBCT, thus cine MRI is considered an excellent device to pre-select the appropriate image/treatment verification SABR protocol. In abdominal targets implanted markers and cine MRI are preferred due to limited image quality of CBCT with the current version. In selected lung SABR cases (≥8mm motion) the dose delivery of organs at risk (lungs - GTV, chest wall) could be reduced compared to free breathing conditions, however, the treatment time is at least two-folds higher.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31225870

RESUMO

CONTEXT: In obese individuals, adipocyte endocrine function is affected by altered autophagy. Genetic variants in autophagy-related gene 7 (ATG7) correlated with serum chemerin (RARRES2) concentrations. OBJECTIVES: To investigate a functional interplay between chemerin and ATG7, how it may relate to autophagy-mediated adipocyte dysfunction in obesity, and the relevance of genetic ATG7-variants in chemerin physiology. DESIGN: Adipose ATG7-mRNA expression and adiposity measures were available in two human study cohorts. The effect of a high-calorie diet on adipose Rarres2 and Atg7-expression was investigated in mice. In 3T3L1-adipocytes, the effect of Atg7-knockdown on chemerin expression and secretion was studied. The influence of single nucleotide polymorphisms on ATG7-transcription and chemerin physiology were investigated using a luciferase assay. SETTING: Mouse model, clinical trials, in vitro studies. PARTICIPANTS: Native American (n=83) and Caucasian (n=100) cohort. MAIN OUTCOME MEASURE: Adipocyte chemerin expression and secretion. RESULTS: In mice fed a high-calorie diet, adipose Atg7-mRNA expression did not parallel an increase in Rarres2-mRNA expression. ATG7-mRNA expression in human subcutaneous adipose tissue correlated with BMI, fat mass (r > 0.27, P < 0.01), and adipocyte cell size (r > 0.42, P < 0.02). Atg7-knockdown in 3T3L1-adipocytes decreased chemerin secretion by 22% (P < 0.04). Rs2606729 in ATG7 was predicted to alter ATG7-transcription and induced higher luciferase activity in vitro (P < 0.0001). CONCLUSIONS: Human adipose ATG7-mRNA expression relates to measures of adiposity. Atg7-knockdown reduces chemerin secretion from adipocytes in vitro supportive of a functional interplay between ATG7 and chemerin in autophagy-mediated adipocyte dysfunction.

7.
EBioMedicine ; 44: 476-488, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153815

RESUMO

BACKGROUND: In brain, CREB-regulated transcription co-activator 1 (CRTC1) is involved in metabolic dysregulation. In humans a SNP in CRTC1 was associated to body fat percentage and two SNPs affected RNA Pol II binding and chromatin structure, implying epigenetic regulation of CRTC1. We sought to understand the relevance of CRTC1 SNPs, DNA methylation and expression in human eating behaviour and its relationship to clinical variables of obesity in blood and adipose tissue. METHODS: 13 CRTC1 SNPs were included to analyze eating behaviour. For rs7256986, follow up association analyses were applied on DNA methylation, CRTC1 expression and clinical parameters. Linear regression was used throughout the study adjusted for age, sex and BMI. Besides data extraction from previous work, rs7256986 was de-novo genotyped and DNA methylation was evaluated by using pyrosequencing. FINDINGS: We found several SNPs in the CRTC1 locus nominally associated with human eating behaviour or 2hr postprandial insulin levels and observed a correlation with alcohol and coffee intake (all P < 0.05). G-allele carriers of rs7256986 showed slightly increased hip circumference. We showed that rs7256986 represents a methylation quantitative trait locus (meQTL) in whole blood and adipose tissue. The presence of the SNP and/or DNA methylation correlated with CRTC1 gene expression which in turn, related to BMI and fat distribution. INTERPRETATION: Our data support the known role of CRCT1 regulating energy metabolism in brain. Here, we highlight relevance of CRTC1 regulation in blood and adipose tissue. FUND: IFB AdiposityDiseases (BMBF); n609020-Scientia Fellows; Helse-SørØst; DFG: CRC 1052/1 and/2; Kompetenznetz Adipositas, German Diabetes Association.

8.
Am J Hum Genet ; 105(1): 15-28, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31178129

RESUMO

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

9.
J Chem Phys ; 150(16): 164119, 2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31042906

RESUMO

The SCAN meta-generalized gradient approximation (GGA) functional is known to describe multiple properties of various materials with different types of bonds with greater accuracy, compared to the widely used PBE GGA functional. Yet, for alkali metals, SCAN shows worse agreement with experimental results than PBE despite using more information about the system. In the current study, this behavior for alkali metals is explained by identifying an inner semicore region which, within SCAN, contributes to an underbinding. The inner semicore push toward larger lattice constants is a general feature but is particularly important for very soft materials, such as the alkali metals, while for harder materials the valence region dominates.

10.
Sci Rep ; 9(1): 7860, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133673

RESUMO

Regulation of the parasympathetic nervous system, indexed through high frequency heart rate variability (HF-HRV), is indicative of physical and psychological health. However, little is known about the trainability of this capacity. We investigated the effects of a 9-month mental training program (the ReSource Project; n = 298) on voluntary HF-HRV upregulation, assessed with a novel biofeedback procedure. The program consisted of attentional, interoceptive, socio-affective and socio-cognitive training elements, all of which potentially influence parasympathetic regulation. Based on known links between oxytocin and parasympathetic activity, we also explored the relationship of HF-HRV upregulation to the oxytocin receptor system. We found that HF-HRV during the biofeedback session increased after 3 months of training, concomitant with prolonged respiration cycles. Breathing-controlled changes in HF-HRV upregulation, indicative of improved parasympathetic control, were significantly increased after 6 months of training. Homozygous risk allele carriers (AA) of the oxytocin receptor gene polymorphism rs53576 showed initially lower parasympathetic control, but fully compensated for their initial deficits through the training. No changes were found for HF-HRV at rest. Our data demonstrate that a mental training intervention extending over several months can increase the capacity for voluntary regulation of HF-HRV, with important implications for improving individual and societal health.

11.
Anim Sci J ; 90(6): 769-773, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30977236

RESUMO

Polyunsaturated fatty acid consumption has been shown to improve insulin sensitivity. We studied if administration of broth with beef meat enriched with polyunsaturated fatty acids influenced glucose-stimulated insulin release in healthy male volunteers. Broth was made either from cattles undergone dietary supplementation with lightly bruised whole linseed in addition to feeding ad libitum on grass silage (test meal) or from those fed grass silage alone (control meal). Oral glucose tolerance tests (OGTT) were performed in patients after a 6-day period of eating 300 ml broth containing 100 g meat once a day in addition to their otherwise normal mixed nourishment. During OGTT, blood samples were taken for blood glucose level and plasma insulin immunoreactivity before and 15, 30, 60, 90, 120, and 180 min after the glucose load. Glucose-stimulated maximum increase in plasma insulin immunoreactivity was 42 ± 6.6 and 81 ± 7.4 mU/ml (p < 0.05) after the test and the control meals, respectively. However, both fasting and postload blood glucose levels were the same after either meal period. The results suggest an insulin-sensitizing effect of food produced from beef cattle maintained on linseed diet in healthy human volunteers.

13.
Neuroimage Clin ; 23: 101803, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30991304

RESUMO

Increased fMRI food cue reactivity in obesity, i.e. higher responses to high- vs. low-calorie food images, is a promising marker of the dysregulated brain reward system underlying enhanced susceptibility to obesogenic environmental cues. Recently, it has also been shown that weight loss interventions might affect fMRI food cue reactivity and that there is a close association between the alteration of cue reactivity and the outcome of the intervention. Here we tested whether fMRI food cue reactivity could be used as a marker of diet-induced early changes of neural processing in the striatum that are predictive of the outcome of the weight loss intervention. To this end we investigated the relationship between food cue reactivity in the striatum measured one month after the onset of the weight loss program and weight changes obtained at the end of the six-month intervention. We observed a significant correlation between BMI change measured after six months and early alterations of fMRI food cue reactivity in the striatum, including the bilateral putamen, right pallidum, and left caudate. Our findings provide evidence for diet-induced early alterations of fMRI food cue reactivity in the striatum that can predict the outcome of the weight loss intervention.

14.
Lipids ; 54(4): 203-210, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30883766

RESUMO

VASPIN, visceral adipose tissue-derived serpin, is an adipokine ameliorating insulin resistance in obesity. Here, we investigated the role of VASPIN and its genetic variants in lipid metabolism. We measured serum VASPIN concentrations by ELISA in 823 metabolically well-characterized Caucasian subjects (Sorbs from Germany). Furthermore, we genotyped 30 representative single nucleotide polymorphisms (SNP) in two independent cohorts with metabolic phenotyping, the Sorbs (N = 823) and Leipzig (N = 919), and conducted genotype-phenotype association analyses. Circulating VASPIN strongly correlated with triacylglycerol levels (TAG; p = 1.079 × 10-11 ), and moderately with apolipoprotein A1 and low-density lipoprotein cholesterol (p = 0.026). Genetic variants in VASPIN were nominally associated with cholesterol, high-density and low-density lipoprotein (HDL-chol, LDL-chol), lipoprotein A, and apolipoprotein B as well as with TAG and free fatty acids (all p < 0.05 adjusted for age, sex, and body mass index [BMI]). Mendelian randomization analysis using VASPIN SNP as an instrumental variable showed borderline influence of VASPIN on LDL-chol levels (p = 0.05). Associations of VASPIN and its genetic variation with metabolic traits suggest a role of VASPIN in human lipid metabolism.


Assuntos
Adipocinas/sangue , Serpinas/sangue , Adulto , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Metabolismo dos Lipídeos/fisiologia , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Triglicerídeos/sangue
15.
Cell Stem Cell ; 24(2): 206-207, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30735647

RESUMO

In a recent study published in Cell Stem Cell, Hu et al. (2019) used human adipose stem cell-derived adipocytes to demonstrate that genetic variation predicts anti-diabetic response to thiazolidinediones (TZDs) by modulating PPARγ binding.

16.
Adipocyte ; 8(1): 51-60, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30676227

RESUMO

Obesity, a condition most commonly associated with hyper-leptinemia, is also characterized by increased expression of autophagy genes and likely autophagic activity in human adipose tissue (AT). Indeed, circulating leptin levels were previously shown to positively associate with the expression levels of autophagy genes such as Autophagy related gene-5 (ATG5). Here we hypothesized that leptin acts in an autocrine-paracrine manner to increase autophagy in two major AT cell populations, adipocytes and macrophages. We followed the dynamics of autophagosomes following acute leptin administration with or without a leptin receptor antagonist (SMLA) using high-throughput live-cell imaging in murine epididymal adipocyte and macrophage (RAW264.7) cell-lines. In macrophages leptin exerted only a mild effect on autophagy dynamics, tending to attenuate autophagosomes growth rate. In contrast, leptin-treated adipocytes exhibited a moderate, ~20% increase in the rate of autophagosome growth, an effect that was blocked by SMLA. This finding corresponded to mild increases in mRNA and protein expression of key autophagy genes. Interestingly, a long-lived proteins degradation assay uncovered a robust, >2-fold leptin-mediated stimulation of the autophagy/lysosome-related (bafilomycin-inhibited) activity, which was entirely blocked by SMLA. Collectively, leptin regulates autophagy in a cell-type specific manner. In adipocytes, autophagosome dynamics is moderately enhanced, but even more pronounced stimulation is seen in autophagy-related long-lived protein degradation. These findings suggest a causal link between obesity-associated hyperleptinemia and elevated adipocyte and AT autophagy-related processes.

17.
Eur J Obstet Gynecol Reprod Biol ; 233: 58-63, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30580224

RESUMO

OBJECTIVE: Continuous monitoring of embryos via time-lapse (TL) provides more information on embryo kinetics and morphology compared to standard daily evaluation. Embryo selection by TL could support single embryo transfer (SET). With SET multiple gestations are avoided and perinatal outcome is improved. Our primary goal was to determine whether selection of a single blastocyst based on an algorithm comprising kinetic and morphologic scores assessed through continuous TL monitoring results in superior clinical outcome compared to embryo selection based on morphology alone. A secondary goal was to assess whether a time-lapse score based on kinetic and morphologic parameters was predictive of implantation. STUDY DESIGN: Randomized controlled trial performed in two private IVF centers in Hungary. Infertile couples scheduled to undergo 1st or 2nd IVF cycles were enrolled. Female age had to be under 36 years. The intervention was embryo evaluation/selection based on TL algorithm. Patients were randomized to SET with TL monitoring (TL-eSET) vs. SET with standard evaluation (control-eSET). Assuming an increase in pregnancy from 44% to 58%, a sample size of 202 per group was calculated based on the interim analysis at 10% information fraction. The primary outcome of the study was pregnancy rate. Secondary outcomes were miscarriage rates, live birth, perinatal outcome and the ability of a time-lapse score constructed based on kinetic and morphologic parameters to predict implantation. Chi-square tests, likelihood-ratio tests and exact tests were used for the analysis of categorical variables. Continuous variables were compared using independent group t-test and analysis of variance. RESULTS: The study was closed after three years. Eventually 161 patients were randomized and analyzed (N = 80 TL-eSET and N = 81 control-eSET). Pregnancy rate did not significantly differ between the groups though there was a trend favoring TL selection (TL-eSET: 46.3% vs control-eSET: 34.6%, p = 0.150; OR: 1.628 (95% CI: 0.857-3.092)). The time-lapse score based on morphologic and kinetic parameters was significantly higher for blastocysts that implanted vs. those that did not (14.5 ± 1.8 vs. 12.1 ± 2.9, p = 0.0001). There were no adverse effects of the intervention. CONCLUSIONS: Selection of a single blastocyst based on information derived from time-lapse monitoring can aid embryo selection for SET.


Assuntos
Coeficiente de Natalidade , Técnicas de Cultura Embrionária/métodos , Implantação do Embrião , Transferência de Embrião Único/métodos , Adulto , Algoritmos , Desenvolvimento Embrionário , Feminino , Fertilização In Vitro , Humanos , Nascimento Vivo , Gravidez , Imagem com Lapso de Tempo
18.
Obes Facts ; 11(6): 475-490, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30537708

RESUMO

BACKGROUND/AIMS: Altered expression and circulating levels of glutathione peroxidase 3 (GPX3) have been observed in obesity and type 2 diabetes (T2D) across species. Here, we investigate whether GPX3 serum concentrations and adipose tissue (AT) GPX3 mRNA expression are related to obesity and weight loss. METHODS: GPX3 serum concentration was measured in 630 individuals, including a subgroup (n = 293) for which omental and subcutaneous (SC) GPX3 mRNA expression has been analyzed. GPX3 analyses include three interventions: 6 months after bariatric surgery (n = 80) or combined exercise/hypocaloric diet (n = 20) or two-step bariatric surgery (n = 24) studies. RESULTS: Bariatric surgery-induced weight loss (-25.8 ± 8.4%), but not a moderate weight reduction of -8.8 ± 6.5% was associated with significantly reduced GPX3 serum concentrations. GPX3 mRNA is significantly higher expressed in AT from individuals with normal glucose metabolism compared to T2D patients. SC AT GPX3 expression is significantly higher in lean compared to obese as well as in insulin-sensitive compared insulin-resistant individuals with obesity. Weight loss after bariatric surgery causes a significant increase in SC AT GPX3 expression. AT GPX3 expression significantly correlates with age, BMI, fat distribution, insulin sensitivity (only SC AT), but not with circulating GPX3. CONCLUSION: Our data support the notion that SC AT GPX3 expression is associated with obesity, fat distribution and related to whole body insulin resistance.


Assuntos
Glutationa Peroxidase/sangue , Glutationa Peroxidase/genética , Obesidade/sangue , Obesidade/genética , Gordura Subcutânea/metabolismo , Perda de Peso/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cirurgia Bariátrica , Distribuição da Gordura Corporal , Estudos de Coortes , Terapia Combinada , Estudos Transversais , Dieta Redutora , Terapia por Exercício , Feminino , Glutationa Peroxidase/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina/genética , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/cirurgia , Estudos Prospectivos , Adulto Jovem
19.
Orv Hetil ; 159(46): 1876-1881, 2018 Nov.
Artigo em Húngaro | MEDLINE | ID: mdl-30450938

RESUMO

The mechanical circulatory support (MCS) program of the Semmelweis University Heart and Vascular Centre has become established over the last five years. The main requirements of our MCS program to be developed first were the Heart Transplantation and Heart Failure Intensive Care Unit and a well trained medical team. The wide range of mechanical circulatory support devices provides suitable background for the adequate treatment of our patients in all indications. In this review, we present our results related to extracorporeal membrane oxygenation (ECMO) supports performed in the last five years. Between 2012 and 2017, we applied MCS support in 140 cases, among them 111 patients received ECMO support. The leading indications of ECMO support were the following: primary graft failure after heart transplantation (33 cases), postcardiotomy cardiogenic shock (18 patients), acute decompensation of end-stage heart failure (14 patients), acute myocardial infarction complicated with refractory cardiogenic shock (37 patients), cardiogenic shock developed after transcatheter aortic valve implantation (3 patients), malignant arrhythmia due to drug intoxication (1 patient) and acute respiratory distress syndrome (4 cases). The mortality of patients receiving ECMO support was 46%. The analysis of the results of ECMO support needs to change our approach. The mortality results show that we lost the half of our patients. However, the mortality in the conventionally treated patients would have been 100% without ECMO. In fact, we could save the life of half of these patients. Orv Hetil. 2018; 159(46): 1876-1881.

20.
Metabolism ; 2018 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-30399374

RESUMO

Obesity is among the most threatening health burdens worldwide and its prevalence has markedly increased over the last decades. Obesity maybe considered a heritable trait. Identifications of rare cases of monogenic obesity unveiled that hypothalamic circuits and the brain-adipose axis play an important role in the regulation of energy homeostasis, appetite, hunger and satiety. For example, mutations in the leptin gene cause obesity through almost unsuppressed overeating. Common (multifactorial) obesity, most likely resulting from a concerted interplay of genetic, epigenetic and environmental factors, is clearly linked to genetic predisposition by multiple risk variants, which, however only account for a minor part of the general BMI variability. Although GWAS opened new avenues in elucidating the complex genetics behind common obesity, understanding the biological mechanisms relative to the specific risk contributing to obesity remains poorly understood. Non-genetic factors such as eating behavior or physical activity strongly modulate the individual risk for developing obesity. These factors may interact with genetic predisposition for obesity through epigenetic mechanisms. Thus, here, we review the current knowledge about monogenic and common (multifactorial) obesity highlighting the important recent advances in our knowledge on how epigenetic regulation is involved in the etiology of obesity.

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