RESUMO
Background: Sphingolipids are components of cell membrane structure, but also circulate in serum and are essential mediators of many cellular functions. While ceramides have been proposed previously as a useful biomarker for cardiometabolic disease, the involvement of other sphingolipids is still controversial. The aim of this study was to investigate the cross-sectional association between blood sphingolipidomic profiles and metabolic syndrome (MetS) as well as other atherosclerotic risk factors in a large population-based study in the U.S. Methods: Clinical data and serum sphingolipidomic profiling from 2,063 subjects who participated in the biomarker project of the Midlife in the United States (MIDUS) study were used. Results: Consistent with previous reports, we found a positive association between most ceramide levels and obesity, atherogenic dyslipidemia, impaired glucose metabolism, and MetS prevalence. In contrast, most simple ß-glycosphingolipids (i.e., hexosylceramides and lactosylceramides) were inversely associated with dysmetabolic biomarkers. However, this latter sphingolipid class showed a positive link with inflammatory and vascular damage-associated biomarkers in subjects with MetS. Through metabolic network analysis, we found that the relationship between ceramides and simple ß-glycosphingolipids differed significantly not only according to MetS status, but also with respect to the participants' C-reactive protein levels. Conclusion: Our findings suggest that a comprehensive sphingolipid profile is more informative about MetS than ceramides alone, and it may reveal new insights into the pathophysiology and further diabetic vs. cardiovascular risk in patients with MetS.
RESUMO
Emerging research has linked psychological well-being with many physiological markers as well as morbidity and mortality. In this analysis, the relationship between components of eudaimonic well-being and serum sphingolipids levels was investigated using data from a large national survey of middle-aged American adults (Midlife in the United States). Health behaviors (i.e., diet, exercise, and sleep) were also examined as potential mediators of these relationships. Serum levels of total ceramides-the main molecular class of sphingolipids previously associated with several disease conditions-were inversely linked with environmental mastery. In addition, significant correlations were found between specific ceramide, dihydroceramide, and hexosylceramides species with environmental mastery, purpose in life, and self-acceptance. Using hierarchical regression and mediation analyses, health behaviors appeared to mediate these associations. However, the link between ceramides and environmental mastery was partially independent of health behaviors, suggesting the role of additional mediating factors. These findings point to sphingolipid metabolism as a novel pathway of health benefits associated with psychological well-being. In particular, having a sense of environmental mastery may promote restorative behaviors and benefit health via improved blood sphingolipid profiles.
Assuntos
Ceramidas/sangue , Esfingolipídeos/sangue , População Branca , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Depressão/tratamento farmacológico , Depressão/epidemiologia , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Controle Interno-Externo , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Autonomia Pessoal , Qualidade de Vida , Autoimagem , Autoeficácia , Sono , Estados Unidos/epidemiologia , População Branca/psicologiaRESUMO
OBJECTIVE: To investigate the impact of maternal stress during pregnancy on newborn iron and stage 1 iron deficiency at 1 year of age. STUDY DESIGN: In total, 245 mothers and their newborn infants (52% male; 72% white) were recruited at the Meriter Hospital Birthing Center on the basis of known risk factors for iron deficiency. Umbilical cord blood hemoglobin and zinc protoporphyrin/heme (ZnPP/H) were determined to evaluate erythrocyte iron and plasma ferritin was determined to reflect storage iron. Mothers retrospectively reported stress experienced previously during pregnancy on a 25-item questionnaire. Blood was also was collected from 79 infants who were breastfed at 1 year of age. RESULTS: Maternal recall of distress and health concerns during pregnancy correlated with cord blood ZnPP/H indices (r = 0.21, P < .01), even in the absence of major traumatic events. When concurrent with other known risks for iron deficiency, including maternal adiposity, socioeconomic status, and race, maternal stress had a summative effect, lowering cord blood iron. At 1 year, 24% of infants who were breastfed had moderate iron deficiency (plasma ferritin <12 µg/L). Higher cord blood ZnPP/H was predictive of this moderate iron deficiency (95% CI 0.26-1.47, P = .007). When coincident with maternal reports of gestational stress, the likelihood of low plasma ferritin at 1 year increased 36-fold in breastfed infants as compared with low-stress pregnancies (95% CI 1.33-6.83, P = .007). CONCLUSIONS: Maternal recall of stress during pregnancy was associated with lower iron stores at birth. High cord blood ZnPP/H, reflecting low erythrocyte iron, was correlated with the likelihood of stage 1 iron deficiency at 1 year, when rapid growth can deplete storage iron in breastfed infants.
Assuntos
Anemia Ferropriva/sangue , Recém-Nascido Prematuro/sangue , Exposição Materna/efeitos adversos , Complicações na Gravidez , Estresse Psicológico/sangue , Adolescente , Adulto , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/etiologia , Feminino , Ferritinas/sangue , Seguimentos , Idade Gestacional , Hemoglobinas/metabolismo , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Wisconsin/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To determine the impact of maternal obesity and gestational weight gain across pregnancy on fetal indices of inflammation and iron status. STUDY DESIGN: Eighty-five healthy term newborns delivered via elective cesarean were categorized by 2 maternal body mass index (BMI) thresholds; above or below 30 kg/m(2) or above or below 35 kg/m(2). Umbilical cord plasma levels of C-reactive protein, interleukin (IL)-6, tumor necrosis factor (TNF)-α, ferritin, and hepcidin were assayed. Cytokines released by phytohemagglutinin-stimulated umbilical cord mononuclear cells (MNCs) were assayed. RESULTS: Maternal class II obesity, defined as BMI of 35 kg/m(2) and above, predicted higher C-reactive protein and TNF-α in umbilical cord plasma (P < .05 for both), and also proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) from stimulated MNC (P < .05 for all). The rise in plasma TNF-α and MNC TNF-α was not linear but occurred when the threshold of BMI 35 kg/m(2) was reached (P < .005, P < .06). Poorer umbilical cord iron indices were associated with maternal obesity. When ferritin was low, IL-6 was higher (P < .04), but this relationship was present primarily when maternal BMI exceeded 35 kg/m(2) (P < .03). Ferritin was correlated with hepcidin (P < .0001), but hepcidin was unrelated to either maternal BMI or inflammatory indices. CONCLUSIONS: Class II obesity and above during pregnancy is associated with fetal inflammation in a threshold fashion. Although maternal BMI negatively impacted fetal iron status, hepcidin, related to obesity in adults, was related to iron status and not obesity in fetuses. Pediatricians should be aware of these relationships.