Healthy plasma lipidomic signatures depend on sex, age, body mass index, and contraceptives but not perceived stress
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ABSTRACT:
ORGANISM(S): Homo sapiens (human)
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PROVIDER: S-BSST1489 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:ContextStudies on 24-h cortisol secretion are rare. The impact of sex, age and adiposity on cortisol levels, often restricted to one or a few samples, are well recognized, but conflicting.ObjectiveTo investigate cortisol dynamics in 143 healthy men and women, spanning 7 decades and with a 2-fold body mass index (BMI) range with different analytic tools.SettingClinical Research Unit.DesignCortisol concentrations in 10-min samples collected for 24 h. Outcomes were mean levels, deconvolution parameters, approximate entropy (ApEn, regularity statistic) and 24-h rhythms.ResultsTotal 24-h cortisol secretion rates estimated by deconvolution analysis were sex, age and BMI independent. Mean 24-h cortisol concentrations were lower in premenopausal women than those in men of comparable age (176 ± 8.2 vs 217 ± 9.4 nmol/L, P = 0.02), but not in subjects older than 50 years. This was due to lower daytime levels in women, albeit similar in the quiescent overnight period. Aging increased mean cortisol by 10 nmol/L per decade during the quiescent secretory phase and advanced the acrophase of the diurnal rhythm by 24 min/decade. However, total 24-h cortisol secretion rates estimated by deconvolution analysis were sex, age and BMI independent. ApEn of 24-h profiles was higher (more random) in premenopausal women than those in men (1.048 ± 0.025 vs 0.933 ± 0.023, P = 0.001), but not in subjects older than 50 years. ApEn peaked during the daytime.ConclusionSex and age jointly determine the 24-h cortisol secretory profile. Sex effects are largely restricted to age <50 years, whereas age effects elevate concentrations in the late evening and early night and advance the timing of the peak diurnal rhythm.
| S-EPMC5597974 | biostudies-literature
Project description:PurposeHemodilution refers to reduced concentrations of analytes in the blood secondary to increased fluid volume. Given that obesity is associated with expanded vascular volume, hemodilution may result in a lower ratio of blood concentrations of analytes among heavier subjects. Assessing the relationship of hormone concentration to total mass varies by body mass index (BMI) is etiologically important because obesity is related to hormone metabolism and cancer risk.MethodsWe evaluated data for 194 postmenopausal controls in an endometrial cancer case-control study. Height, weight, and serum hormone concentrations were measured previously. We estimated serum hormone mass from concentration based on estimates of calculated plasma volume. We assessed the effect of BMI on relationships of sex steroid hormone concentration and mass using multivariate linear regression.ResultsHigher BMI was associated with increased estrone, estrone sulfate, estradiol, and albumin-bound estradiol concentrations and masses (p-trend ≤ 0.001). With increasing BMI, androstenedione concentration did not change significantly (p-trend = 0.548), but its mass increased (p-trend = 0.024).ConclusionsRelationships of sex steroid hormone concentration and mass were generally similar, except for androstenedione in which the relationship was only significant for mass. Future studies to assess both sex steroid hormone concentration and mass may have value in etiological research.
| S-EPMC3090465 | biostudies-literature
Project description:The growing obesity “epidemic” has shed light on its negative impact on overall health status, not only in relation to cardiovascular disorders and metabolic syndrome, but also in regard to its influence on a variety of other health conditions, including autoimmune diseases, such as Multiple Sclerosis (MS). High Body Mass index (BMI) is a risk factor for MS, however, it is not known whether and how it could impact disease course. Several studies, including those on the Dutch Famine, have highlighted the role of epigenetic modifications in mediating phenotypic changes in response to metabolic shifts, suggesting that epigenetic changes could be a potential mechanism for BMI-driven differences in disease course. Using the Illumina 450K array, we identified genome-wide differences in DNA methylation between blood monocytes from therapy-naïve RRMS patients with high BMI compared to low BMI. Differences were subtle, however, were heavily skewed in the positive direction in the high BMI group, indicative of overall DNA hypermethylation. Further curation of differentially methylated genes, using stringent criteria, revealed enrichment in anti-inflammatory functions among the top hypermethylated genes. Thus, epigenomic changes related to inflammatory processes of monocytes are detected in MS patients with high BMI compared to those with low BMI and could potentially impact disease course by modulating immune-driven neurotoxicity.
2019-06-20 | GSE103929 | GEO
Project description:BACKGROUND:Perceived neighborhood characteristics are linked to obesity, however, the mechanisms linking these two factors remain unknown. PURPOSE:This study aimed to examine associations between perceived neighborhood characteristics and body mass index (BMI), establish whether indirect pathways through psychological distress and inflammation are important, and determine whether these associations vary by race/ethnicity. METHODS:Participants were 1,112 adults enrolled in the Texas City Stress and Health Study. Perceived neighborhood characteristics were measured using the Perceived Neighborhood Scale. Psychological distress was measured with the Center for Epidemiological Studies Depression Scale, Perceived Stress Scale and mental health subscale of the Short Form Health Survey-36. Markers of inflammation included C-reactive protein, interleukin-6, and tumor necrosis factor receptor-1. Associations were examined with Structural Equation Modeling. RESULTS:A model linking neighborhood characteristics with BMI through direct and indirect (i.e., psychological distress and inflammation) paths demonstrated good fit with the data. Less favorable perceived neighborhood characteristics were associated with greater psychological distress (B = -0.87, ? = -0.31, p < .001) and inflammation (B = -0.02, ? = -0.10, p = .035). Psychological distress and inflammation were also significantly associated with BMI (Bdistress = 0.06, ? = 0.08, p = .006; Binflammation = 4.65, ? = 0.41, p < .001). Indirect paths from neighborhood characteristics to BMI via psychological distress (B = -0.05, ? = -0.03, p = .004) and inflammation (B = -0.08, ? = -0.04, p = .045) were significant. In multiple group analysis, a model with parameters constrained equal across race/ethnicity showed adequate fit suggesting associations were comparable across groups. CONCLUSION:Our study extends the literature by demonstrating the importance of neighborhood perceptions as correlates of BMI across race/ethnicity, and highlights the role of psychological and physiological pathways.
| S-EPMC7317154 | biostudies-literature
Project description:Gut-derived serotonin (5-HT) is released from enterochromaffin (EC) cells in response to nutrient cues, and acts to slow gastric emptying and modulate gastric motility. Rodent studies also evidence a role for gut-derived 5-HT in the control of hepatic glucose production, lipolysis and thermogenesis, and in mediating diet-induced obesity. EC cell number and 5-HT content is increased in the small intestine of obese rodents and human, however, it is unknown whether EC cells respond directly to glucose in humans, and whether their capacity to release 5-HT is perturbed in obesity. We therefore investigated 5-HT release from human duodenal and colonic EC cells in response to glucose, sucrose, fructose and α-glucoside (αMG) in relation to body mass index (BMI). EC cells released 5-HT only in response to 100 and 300 mM glucose (duodenum) and 300 mM glucose (colon), independently of osmolarity. Duodenal, but not colonic, EC cells also released 5-HT in response to sucrose and αMG, but did not respond to fructose. 5-HT content was similar in all EC cells in males, and colonic EC cells in females, but 3 to 4-fold higher in duodenal EC cells from overweight females (p < 0.05 compared to lean, obese). Glucose-evoked 5-HT release was 3-fold higher in the duodenum of overweight females (p < 0.05, compared to obese), but absent here in overweight males. Our data demonstrate that primary human EC cells respond directly to dietary glucose cues, with regional differences in selectivity for other sugars. Augmented glucose-evoked 5-HT release from duodenal EC is a feature of overweight females, and may be an early determinant of obesity.
| S-EPMC6412251 | biostudies-literature
Project description:BackgroundElectrocardiogram (ECG) measured QRS duration has been shown to influence cardiovascular outcomes. However, there is paucity of data on whether ECG QRS duration is influenced by obesity and sex in large populations.MethodsAll ECGs performed by a pathology provider over a 2-year period were included. ECGs with confounding factors and those not in sinus rhythm were excluded from the primary analysis.ResultsOf the 76,220 who met the inclusion criteria, 41,685 (55%) were females. The median age of the study cohort was 61 years (interquartile [IQR] range 48-71 years). The median QRS duration was 86 ms (IQR 80-94 ms). The median BMI was 27.6 kg/m2 (IQR 24.2-31.8 kg/m2). When stratified according to the World Health Organization classification of BMI < 18.50 kg/m2, 18.50-24.99 kg/m2, 25.00-29.99 kg/m2, and ≥ 30.00 kg/m2, the median QRS durations were 82 ms (IQR 76-88 ms), 86 ms (IQR 80-92 ms), 88 ms (IQR 80-94 ms) and 88 ms (IQR 82-94 ms), respectively (p < 0.001 for linear trend). Median QRS duration for females was 84 ms (IQR 78-88 ms); for males, it was 92 ms (IQR 86-98 ms), p < 0.001. Compared to males, females had narrower QRS complexes at similar age and similar BMI. In multiple linear regression analysis, BMI correlated positively with QRS duration (standardized beta 0.095, p < 0.001) independent of age, sex, and heart rate.ConclusionsIn this large cohort there was a positive association between increasing BMI and QRS duration. Females had narrower QRS duration than males at similar age and similar BMI.
| S-EPMC8503593 | biostudies-literature
Project description:RationaleObesity hypoventilation syndrome (OHS) is often underdiagnosed, with significant morbidity and mortality. Bicarbonate, as a surrogate of arterial carbon dioxide, has been proposed as a screening tool for OHS. Understanding the predictors of serum bicarbonate could provide insights into risk factors for OHS. We hypothesized that the bicarbonate levels would increase with an increase in body mass index (BMI), since the prevalence of OHS increases with obesity.MethodsWe used the TriNetX Research Network, an electronic health record database with de-identified clinical data from participating healthcare organizations across the United States, to identify 93,320 adults without pulmonary or advanced renal diseases who had serum bicarbonate and BMI measurements within 6 months of each other between 2017 and 2022. We used linear regression analysis to examine the associations between bicarbonate and BMI, age, and their interactions for the entire cohort and stratified by sex. We also applied a non-linear machine learning algorithm (XGBoost) to examine the relative importance of age, BMI, sex, race/ethnicity, and obstructive sleep apnea (OSA) status on bicarbonate.ResultsThis cohort population was 56% women and 72% white and 80% non-Hispanic individuals, with an average (SD) age of 49.4 (17.9) years and a BMI of 29.1 (6.1) kg/m2. The mean bicarbonate was 24.8 (2.8) mmol/L, with higher levels in men (mean 25.2 mmol/L) than in women (mean 24.4 mmol/L). We found a small negative association between bicarbonate and BMI, with an expected change of -0.03 mmol/L in bicarbonate for each 1 kg/m2 increase in BMI (p < 0.001), in the entire cohort and both sexes. We found sex differences in the bicarbonate trajectory with age, with women exhibiting lower bicarbonate values than men until age 50, after which the bicarbonate levels were modestly higher. The non-linear machine learning algorithm similarly revealed that age and sex played larger roles in determining bicarbonate levels than the BMI or OSA status.ConclusionContrary to our hypothesis, BMI is not associated with elevated bicarbonate levels, and age modifies the impact of sex on bicarbonate.
| S-EPMC10512520 | biostudies-literature
Project description:Spontaneous preterm birth (sPTB) is a major cause of infant morbidity and mortality. While metabolic changes leading to preterm birth are unknown, several factors including dyslipidemia and inflammation have been implicated and paradoxically both low (<18.5 kg/m2) and high (>30 kg/m2) body mass indices (BMIs) are risk factors for this condition. The objective of the study was to identify BMI-associated metabolic perturbations and potential mid-gestation serum biomarkers of preterm birth in a cohort of underweight, normal weight and obese women experiencing either sPTB or full-term deliveries (n = 102; n = 17/group). For this purpose, we combined untargeted metabolomics and lipidomics with targeted metabolic profiling of major regulators of inflammation and metabolism, including oxylipins, endocannabinoids, bile acids and ceramides. Women who were obese and had sPTB showed elevated oxidative stress and dyslipidemia characterized by elevated serum free fatty acids. Women who were underweight-associated sPTB also showed evidence of dyslipidemia characterized by elevated phospholipids, unsaturated triglycerides, sphingomyelins, cholesteryl esters and long-chain acylcarnitines. In normal weight women experiencing sPTB, the relative abundance of 14(15)-epoxyeicosatrienoic acid and 14,15-dihydroxyeicosatrienoic acids to other regioisomers were altered at mid-pregnancy. This phenomenon is not yet associated with any biological process, but may be linked to estrogen metabolism. These changes were differentially modulated across BMI groups. In conclusion, using metabolomics we observed distinct BMI-dependent metabolic manifestations among women who had sPTB. These observations suggest the potential to predict sPTB mid-gestation using a new set of metabolomic markers and BMI stratification. This study opens the door to further investigate the role of cytochrome P450/epoxide hydrolase metabolism in sPTB.
| S-EPMC7671555 | biostudies-literature
Project description:Obesity plays an important role in the development of insulin resistance and diabetes, but the molecular mechanism that links obesity and diabetes is still not completely understood. Here, we used 146 targeted metabolomic profiles from the German KORA FF4 cohort consisting of 1715 participants and associated them with obesity and type 2 diabetes. In the basic model, 83 and 51 metabolites were significantly associated with body mass index (BMI) and T2D, respectively. Those metabolites are branched-chain amino acids, acylcarnitines, lysophospholipids, or phosphatidylcholines. In the full model, 42 and 3 metabolites were significantly associated with BMI and T2D, respectively, and replicate findings in the previous studies. Sobel mediation testing suggests that the effect of BMI on T2D might be mediated via lipids such as sphingomyelin (SM) C16:1, SM C18:1 and diacylphosphatidylcholine (PC aa) C38:3. Moreover, mendelian randomization suggests a causal relationship that BMI causes the change of SM C16:1 and PC aa C38:3, and the change of SM C16:1, SM C18:1, and PC aa C38:3 contribute to T2D incident. Biological pathway analysis in combination with genetics and mice experiments indicate that downregulation of sphingolipid or upregulation of phosphatidylcholine metabolism is a causal factor in early-stage T2D pathophysiology. Our findings indicate that metabolites like SM C16:1, SM C18:1, and PC aa C38:3 mediate the effect of BMI on T2D and elucidate their role in obesity related T2D pathologies.
| S-EPMC9965667 | biostudies-literature
Project description:Gut microbiota is considered a separate organ with endocrine capabilities, actively contributing to tissue homeostasis. It consists of at least two separate microbial populations, the lumen-associated (LAM) and the mucosa-associated microbiota (MAM). In the present study, we compared LAM and MAM, by collecting stools and sigmoid brush samples of forty adults without large-bowel symptoms, and through a 16S rRNA gene next-generation sequencing (NGS) approach. MAM sample analysis revealed enrichment in aerotolerant Proteobacteria, probably selected by a gradient of oxygen that decreases from tissue to lumen, and in Streptococcus and Clostridium spp., highly fermenting bacteria. On the other hand, LAM microbiota showed an increased abundance in Bacteroides, Prevotella, and Oscillospira, genera able to digest and to degrade biopolymers in the large intestine. Predicted metagenomic analysis showed LAM to be enriched in genes encoding enzymes mostly involved in energy extraction from carbohydrates and lipids, whereas MAM in amino acid and vitamin metabolism. Moreover, LAM and MAM communities seemed to be influenced by different host factors, such as diet and sex. LAM is affected by body mass index (BMI) status. Indeed, BMI negatively correlates with Faecalibacterium prausnitzii and Flavonifractor plautii abundance, putative biomarkers of healthy status. In contrast, MAM microbial population showed a significant grouping according to sex. Female MAM was enriched in Actinobacteria (with an increased trend of the genus Bifidobacterium), and a significant depletion in Veillonellaceae. Interestingly, we found the species Gemmiger formicilis to be associated with male and Bifidobacterium adolescentis, with female MAM samples. In conclusion, our results suggest that gut harbors microbial niches that differ in both composition and host factor susceptibility, and their richness and diversity may be overlooked evaluating only fecal samples.
| S-EPMC5817072 | biostudies-literature