The Role of Phosphatidylethanolamine N-Methyltransferase () and Its Waist-Hip-Ratio-Associated Locus rs4646404 in Obesity-Related Metabolic Traits and Liver Disease.

In previous genome-wide association studies (GWAS), genetic loci associated with obesity and impaired fat distribution (FD) have been identified. In the present study, we elucidated the role of the gene, including the waist-hip-ratio-associated single nucleotide polymorphism rs4646404, and its influence on obesity-related metabolic traits. DNA from 2926 metabolically well-characterized subjects was used for genotyping.

Sex-Specific Effects of the Genetic Variant rs10487505 Upstream of in the Development of Obesity.

The SNP rs10487505 in the promotor region of the gene was reported to be associated with decreased circulating leptin and increased body mass index (BMI). However, the phenotypic outcomes affected by rs10487505 in the leptin regulatory pathway have not been systematically studied. Therefore, the aim of this study was to elucidate the influence of rs10487505 on mRNA expression and obesity-related parameters.

Metabolic Effects of the Waist-To-Hip Ratio Associated Locus Are Related to Expression in Adipose Tissue.

locus has been shown to be associated with body fat distribution (FD), but neither the causal gene nor its role in metabolic diseases has been elucidated. We hypothesize that may act as the causal genes for FD-related SNPs (rs10195252 and rs6738627), and that they may be regulated by SNP to effect obesity-related metabolic traits. We genotyped rs10195252 and rs6738627 in 2860 subjects with metabolic phenotypes.

Obesity and COVID-19: What are the Consequences?

Obesity is an increasing health problem all over the world. In combination with the current COVID-19 pandemic, this has turned into a massive challenge as individuals with overweight and obesity at all ages show a significant increase in their risk of getting severe COVID-19. Around 20% of all patients that were hospitalized for COVID-19 suffered from obesity alone, whereas obesity in combination with other metabolic comorbidities, such as type 2 diabetes and hypertension, account for up to 60% of all hospitalizations in relation to COVID-19.

Adipsin Serum Concentrations and Adipose Tissue Expression in People with Obesity and Type 2 Diabetes.

(1) Adipsin is an adipokine that may link increased fat mass and adipose tissue dysfunction to obesity-related cardiometabolic diseases. Here, we investigated whether adipsin serum concentrations and adipose tissue (AT) mRNA expression are related to parameters of AT function, obesity and type 2 diabetes (T2D). (2) Methods: A cohort of 637 individuals with a wide range of age and body weight (Age: 18-85 years; BMI: 19-70 kg/m) with (n = 237) or without (n = 400) T2D was analyzed for serum adipsin concentrations by ELISA and visceral (VAT) and subcutaneous (SAT) mRNA expression by RT-PCR.

Effects of Weight Loss on Glutathione Peroxidase 3 Serum Concentrations and Adipose Tissue Expression in Human Obesity.

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.

DNA methylation of SSPN is linked to adipose tissue distribution and glucose metabolism.

DNA methylation is a crucial epigenetic mechanism in obesity and fat distribution. We explored the Sarcospan ( SSPN) gene locus by using genome-wide data sets comprising methylation and expression data, pyrosequencing analysis in the promoter region, and genetic analysis of an SNP variant rs718314, which was previously reported to associate with waist-to-hip ratio. We found that DNA methylation influences several clinical variables related to fat distribution and glucose metabolism, while SSPN mRNA levels showed directionally opposite effects on these traits.

IRS1 DNA promoter methylation and expression in human adipose tissue are related to fat distribution and metabolic traits.

The SNP variant rs2943650 near IRS1 gene locus was previously associated with decreased body fat and IRS1 gene expression as well as an adverse metabolic profile in humans. Here, we hypothesize that these effects may be mediated by an interplay with epigenetic alterations. We measured IRS1 promoter DNA methylation and mRNA expression in paired human subcutaneous and omental visceral adipose tissue samples (SAT and OVAT) from 146 and 41 individuals, respectively.

Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity.

Objective/methods: DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese obese individuals.

Results: We identified negatively correlated methylation and expression of several obesity-associated genes in our discovery dataset and replicated in two independent cohorts.

Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction.

Recently, a genome-wide analysis identified DNA methylation of the HIF3A (hypoxia-inducible factor 3A) as strongest correlate of BMI. Here we tested the hypothesis that HIF3A mRNA expression and CpG-sites methylation in adipose tissue (AT) and genetic variants in HIF3A are related to parameters of AT distribution and function. In paired samples of subcutaneous AT (SAT) and visceral AT (VAT) from 603 individuals, we measured HIF3A mRNA expression and analyzed its correlation with obesity and related traits.

Measuring Biological Age via Metabonomics: The Metabolic Age Score.

Chronological age is one of the most important risk factors for adverse clinical outcome. Still, two individuals at the same chronological age could have different biological aging states, leading to different individual risk profiles. Capturing this individual variance could constitute an even more powerful predictor enhancing prediction in age-related morbidity.

Fat depot-specific expression of HOXC9 and HOXC10 may contribute to adverse fat distribution and related metabolic traits.

Objective: Independent previous studies in both rodents and humans suggest a role of developmental genes in the origin of obesity and body fat distribution. Here, the hypothesis that human adipose tissue (AT) expression of the developmental genes homeobox transcription factors C9 (HOXC9) and C10 (HOXC10) is fat depot-specific and related to obesity-related traits was tested.

Methods: In 636 individuals, HOXC9 and HOXC10 mRNA expression was investigated in paired abdominal subcutaneous (SC) and omental AT samples in relation to a wide range of age, BMI, fat distribution, and metabolic parameters and in subfractions of isolated adipocytes and cells of the stromal vascular fraction (SVF).

ADCY5 gene expression in adipose tissue is related to obesity in men and mice.

Genome wide association studies revealed an association of the single nucleotide polymorphism rs11708067 within the ADCY5 gene--encoding adenylate cyclase 5--with increased type 2 diabetes (T2D) risk and higher fasting glucose. However, it remains unclear whether the association between ADCY5 variants and glycemic traits may involve adipose tissue (AT) related mechanisms. We therefore tested the hypothesis that ADCY5 mRNA expression in human and mouse AT is related to obesity, fat distribution, T2D in humans and high fat diet (HFD) in mice.

Telomere length differences between subcutaneous and visceral adipose tissue in humans.

Adipocyte hypertrophy and hyperplasia have been shown to be associated with shorter telomere length, which may reflect aging, altered cell proliferation and adipose tissue (AT) dysfunction. In individuals with obesity, differences in fat distribution and AT cellular composition may contribute to obesity related metabolic diseases. Here, we tested the hypotheses that telomere lengths (TL) are different between: (1) abdominal subcutaneous and omental fat depots, (2) superficial and deep abdominal subcutaneous AT (SAT), and (3) adipocytes and cells of the stromal vascular fraction (SVF).

Global DNA methylation levels in human adipose tissue are related to fat distribution and glucose homeostasis.

Aims/hypothesis: Epigenetic alterations may influence the metabolic pathways involved in human obesity. We hypothesised that global DNA methylation levels in adipose tissue might be associated with obesity and related phenotypes.

Methods: We measured global DNA methylation levels in paired samples of subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from 51 individuals, and in leucocytes from 559 Sorbs, a population from Germany, using LUminometric Methylation Assay (LUMA).

Adipose tissue depot specific promoter methylation of TMEM18.

Unlabelled: Epigenetic processes such as dynamic promoter methylation may play a role in obesity, fat distribution and its accompanied metabolic alterations. TMEM18 is a candidate gene for body mass index (BMI) comprising the second largest effect size among all loci identified so far via GWAS. We hypothesized that differential TMEM18 gene expression in visceral (VAT) and subcutaneous adipose tissue (SAT) may be a consequence of depot specific differential methylation at the TMEM18 promoter region.

Adiponectin in coronary heart disease and newly diagnosed impaired glucose tolerance.

Objective: Adiponectin is produced by adipose tissue and regarded as protective hormone for diabetes and coronary heart disease (CHD). Its role in heart failure is discussed controversially.

Methods: In this study, 1015 consecutive patients admitted for acute (n = 149) or elective (n = 866) coronary angiography were enrolled.

Nicotinamide nucleotide transhydrogenase mRNA expression is related to human obesity.

Objective: A spontaneous deletion in the nicotinamide nucleotide transhydrogenase (Nnt) gene eliminating exons 7-11 in C57BL/6J (B6J) mice is associated with reduced glucose-stimulated insulin secretion in vitro, impaired glucose tolerance, higher epigonadal fat mass, and altered susceptibility to diet induced obesity of male B6J mice was proposed. A potential implication for NNT in human adipose tissue distribution has not been investigated so far.

Design And Methods: Therefore, NNT mRNA expression in paired human samples of visceral (vis) and subcutaneous (sc) adipose tissue from 221 subjects with a wide range of body mass index (BMI), insulin sensitivity, and glucose tolerance was analyzed.

Effects of weight loss and exercise on apelin serum concentrations and adipose tissue expression in human obesity.

Objective: Apelin is an adipokine which plays a role in the regulation of glucose homeostasis and may contribute to the link between increased adipose tissue mass and obesity related metabolic diseases. Here we investigate the role of omental and subcutaneous (SC) adipose tissue apelin and its receptor APJ mRNA expression in human obesity and test the hypothesis that changes in circulating apelin are associated with reduced fat mass in three weight loss intervention studies.

Methods: Apelin serum concentration was measured in 740 individuals in a cross-sectional (n = 629) study including a subgroup (n = 161) for which omental and SC apelin mRNA expression has been analyzed and in three interventions: 12 weeks exercise (n = 60), 6 months calorie-restricted diet (n = 19), 12 months after bariatric surgery (n = 32).

Short-term changes of the urine metabolome after bariatric surgery.

Bariatric surgery leads to a loss of excess weight and to a remission of diabetes in a majority of patients. In an attempt to explain these underlying mechanisms, a broad range of metabolic alterations have been suggested. We aimed to investigate short-term changes in the urinary metabolome after bariatric surgery.

Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity.

Chemerin is a chemoattractant adipokine that regulates adipogenesis and may induce insulin resistance. Chemerin serum concentrations are elevated in obese, insulin-resistant, and inflammatory states in vivo. Here we investigate the role of omental (OM) and subcutaneous (SC) adipose tissue chemerin and CMKLR1 messenger RNA (mRNA) expression in human obesity.

Genetic and evolutionary analyses of the human bone morphogenetic protein receptor 2 (BMPR2) in the pathophysiology of obesity.

Objective: Human bone morphogenetic protein receptor 2 (BMPR2) is essential for BMP signalling and may be involved in the regulation of adipogenesis. The BMPR2 locus has been suggested as target of recent selection in human populations. We hypothesized that BMPR2 might have a role in the pathophysiology of obesity.

Enhanced platelet activation by prolactin in patients with ischemic stroke.

Prolactin and leptin are newly recognised platelet co-stimulators due to potentiation of ADP-induced platelet aggregation. Elevated leptin levels have recently been found to be a risk factor for ischemic stroke in both men and women, and especially in combination with increased blood pressure for hemorrhagic stroke in men. Until now an association between hyperprolactinemia and ischemic stroke has not been investigated systematically.