Obesity, Body Fat Distribution, and Cancer Risk in the Multiethnic Cohort
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PROVIDER: PRJNA490404 | ENA |
REPOSITORIES: ENA
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Project description:Obesity, Body Fat Distribution, and Cancer Risk in the Multiethnic Cohort
| PRJNA490403 | ENA
Project description:Multiethnic Cohort (MEC) SIGMA Exome Sequencing Project
| PRJNA398435 | ENA
Project description:CIDR: Multiethnic GWAS of Cancer and related traits in the Multiethnic Cohort (MEC)
| PRJNA671278 | ENA
Project description:CIDR: Multiethnic GWAS of Cancer and related traits in the Multiethnic Cohort (MEC)
| PRJNA671279 | ENA
Project description:Induced pluripotent stem cells (iPSCs), upon differentiation into somatic cell types, offer the ability to model the genetic states of tissues in the individuals from whom the iPSCs were derived. A recent study used a multiethnic cohort of healthy individuals to derive iPSCs and iPSC-hepatocytes and perform gene expression and expression quantitative trait locus analyses, identifying causal genes and variants linked to blood lipid levels.2 We sought to use the same cohort of iPSC lines to generate a similar resource with iPSC-cardiomyocytes and make the results available to the community.
2021-03-01 | GSE146071 | GEO
Project description:Tetrahydrobiopterin (BH4) is an essential cofactor for several metabolic enzymes, including the aromatic amino acid hydroxylases, alkylglycerol mono-oxygenase and NO synthases. BH4 deficiency due to an autosomal recessive defect in its biosynthetic enzyme 6-pyruvoyltetrahydropterin synthase (PTPS, encoded by the PTS gene) leads to a variant form of hyperphenylalaninemia concomitant with severe deficiency of brain monoamine neurotransmitters. In contrast, augmentation of BH4 by pharmacological supplementation or stimulation of its biosynthesis is thought to correct eNOS dysfunction, to protect from (cardio) vascular disease and/or to prevent from abdominal obesity and development of the metabolic syndrome. We have previously reported that complete Pts knock-out (ko) mice die after birth (Elzaouk et al JBC 2003). Here we generated a murine Pts-knock-in (ki) allele expressing a PTPS-p.Arg15Cys mutant enzyme with low residual activity (12% of wild-type in vitro) and investigated heterozygous Pts-ko/wt, homozygous Pts-ki/ki and compound heterozygous Pts-ki/ko mutant mice. All mice were viable and, depending on the severity of the Pts alleles, exhibited up to 90% reduction of PTPS activity in liver and brain tissues concomitant with high neopterin, but neither an elevation of blood L-Phe, nor a decrease in brain monoamine neurotransmitters dopamine or serotonin. Upon a standard systemic and comprehensive phenotyping of Pts-ki/ki mice, we found alterations in energy metabolites with reduced body mass, higher fat content, lower lean mass, and increased blood glucose and cholesterol in mutant animals. Furthermore, heterozygous Pts-ko/wt and/or homozygous Pts-ki/ki mice exhibited increased body weight and elevated intra-abdominal fat tissue when fed with normal chow or high fat diet. We conclude that a reduced BH4-biosynthetic activity in mice leads to abnormal body fat distribution and abdominal obesity potentially through a mildly compromised eNOS function.
2015-06-01 | GSE55148 | GEO
Project description:The effect of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area on metabolic syndrome (MS) has been debated. We aimed to evaluate the effects of VAT and SAT on the incidence of MS and its components in a large and apparently healthy Asian population. We performed a longitudinal cohort study of 1,964 subjects who received health screenings over a 5-year follow-up period; 317 incidents of MS (16.1%) were observed during a median follow-up of 4.5 years. The VAT area was significantly associated with a higher incidence of MS; the adjusted HR for incident MS per 1 SD of VAT was 1.50 (95% CI 1.29-1.74), and the adjusted HR of the 5th VAT quintile compared with the 1st quintile was 3.73 (95% CI 2.22-6.28). However, the SAT area was not associated with incident MS. Although the VAT area was longitudinally associated with the incidence of each component of MS, the SAT area was inversely associated with the risk of high blood pressure, fasting blood sugar, and triglycerides, with marginal significance. In conclusion, the VAT area is longitudinally associated with an increased risk of incident MS, while SAT may have a protective effect against the incidence of individual MS components.
| S-EPMC5591218 | biostudies-literature
Project description:It is recognized that higher height and weight are associated with higher risk of atrial fibrillation or flutter (AF) but it is unclear whether risk of AF is related to body fat, body fat location, or lean body mass.This article reports the Danish population-based prospective cohort Diet, Cancer and Health study conducted among 55,273 men and women 50-64 years of age at recruitment. The associations between bioelectrical impedance derived measures of body composition and combinations of anthropometric measures of body fat distribution and risk of an incident record of AF in the Danish Registry of Patients were investigated.During follow-up (median 13.5 years) AF developed in 1,669 men and 912 women. Higher body fat at any measured location was associated with higher risk of AF. The adjusted hazard ratio (HR) per 1 sex-specific standard deviation (SD) increment in body fat mass was 1.29 (95% confidence interval [CI], 1.24-1.33). Higher lean body mass was also associated with a higher risk of AF. The adjusted HR for 1 sex-specific SD increment was 1.40 (95% CI, 1.35-1.45).Higher body fat and higher lean body mass were both associated with higher risk of AF.
| S-EPMC4169701 | biostudies-literature
Project description:High-fat diet (HFD)-induced obesity is a multi-factorial disease including genetic, physiological, behavioral, and environmental components. Drosophila has emerged as an effective metabolic disease model. Cytidine 5'-triphosphate synthase (CTPS) is a crucial enzyme for the de novo synthesis of CTP, governing the cellular level of CTP and phospholipid synthesis. CTPS has been found to form filaments known as cytoophidia, which are evolutionarily conserved in bacteria, archaea, and eukaryotes. Here, we show that CTPS functions in fat bodies to regulate body weight and starvation resistance in Drosophila. HFD-induced obesity enhances CTPS transcription and lengthens cytoophidia in larval adipocytes. CTPS depletion in the fat body prevented HFD-induced obesity, including body weight gain, adipocyte expansion, and lipid accumulation, by inhibiting the PI3K-Akt-SREBP axis. A dominant-negative form of CTPS also inhibits adipocyte expansion and down-regulates lipogenic genes. As a result, our findings not only establish a functional link between CTPS and lipid homeostasis but also highlight a potential role of CTPS manipulation in the treatment of HFD-induced obesity.
2023-08-30 | GSE221707 | GEO
Project description:Obesity is a well-recognized risk factor for atrial fibrillation (AF), yet adiposity measures other than body mass index (BMI) have had limited assessment in relation to AF risk. We examined the associations of adiposity measures with AF in a biracial cohort of older adults. Given established racial differences in obesity and AF, we assessed for differences by black and white race in relating adiposity and AF.We analyzed data from 2,717 participants of the Health, Aging, and Body Composition Study. Adiposity measures were BMI, abdominal circumference, subcutaneous and visceral fat area, and total and percent fat mass. We determined the associations between the adiposity measures and 10-year incidence of AF using Cox proportional hazards models and assessed for their racial differences in these estimates.In multivariable-adjusted models, 1-SD increases in BMI, abdominal circumference, and total fat mass were associated with a 13% to 16% increased AF risk (hazard ratio [HR] 1.14, 95% CI 1.02-1.28; HR 1.16, 95% CI 1.04-1.28; and HR 1.13, 95% CI 1.002-1.27). Subcutaneous and visceral fat areas were not significantly associated with incident AF. We did not identify racial differences in the associations between the adiposity measures and AF.Body mass index, abdominal circumference, and total fat mass are associated with risk of AF for 10years among white and black older adults. Obesity is one of a limited number of modifiable risk factors for AF; future studies are essential to evaluate how obesity reduction can modify the incidence of AF.
| S-EPMC4575766 | biostudies-literature