Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin D deficiency has been associated with pregnancy complications such as preeclampsia, gestational diabetes, and recurrent miscarriage. Therefore, we hypothesized differences in vitamin D status between healthy [Sprague-Dawley (SD) and Lewis (LW)] and complicated [Brown Norway (BN)] rat pregnancies. In SD, LW, and BN rats, we analyzed the maternal plasma levels of the vitamin D metabolites 25-OH-D and 1,25-(OH)2-D at prepregnancy, pregnancy, and postpartum. Analysis of the active metabolite 1,25-(OH)2-D showed a twofold increase in pregnant SD and LW rats but a nearly 10-fold decrease in pregnant BN rats compared with nonpregnant controls. BN rats had a pregnancy-dependent upregulation of CYP24a1 expression, a key enzyme that inactivates vitamin D metabolites. In contrast, the maternal renal expression of CYP24a1 in SD and LW rats remained constant throughout pregnancy. Analysis of the vitamin D receptor (VDR) indicated that LW and SD but not BN rats experience a pregnancy-induced 10-fold decrease in maternal renal VDR protein levels. Further analysis of bisulfite-converted and genomic DNA indicated that the observed differences in maternal renal regulation of CYP24a1 during pregnancy and lactation are not due to differences in CYP24a1 promoter methylation or single-nucleotide polymorphisms. Finally, supplementation with 1,25-(OH)2-D significantly improved the reproductive phenotype of BN rats by increasing litter size and maternal-fetal weight outcomes. We conclude that BN rats represent a novel animal model of pregnancy-specific vitamin D deficiency that is linked to pregnancy complications. Vitamin D deficiency in BN rats correlates with maternal renal CYP24a1 upregulation followed by CYP27b1 upregulation.
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PMID:Characterization of an animal model of pregnancy-induced vitamin D deficiency due to metabolic gene dysregulation. 2432 17

Gestational diabetes mellitus (GDM) is a type of diabetes and occurs during pregnancy. Brown adipose tissue (BAT) improves glucose homeostasis and mitigates insulin resistance, however, its activity is reduced in GDM. Placenta growth factor (PlGF) is an angiogenic factor produced by placental trophoblasts. Nevertheless, whether and how PlGF could affect BAT function in GDM are not defined. To investigate this question, 91 non-diabetic pregnant participants and 73 GDM patients were recruited to Gynaecology and Obstetrics Centre in Lu He hospital. Serum levels of PlGF were quantified by ELISA. Skin temperature was measured by far infrared thermography in the supraclavicular region where classical BATs were located. The direct effect of PlGF on BAT function was explored using the established human preadipocyte differentiation system. Thereby, we demonstrated that serum levels of PlGF were lower in GDM patients compared with controls, which was accompanied by decreased skin temperature in the supraclavicular region. By qPCR and western blot, mRNA and protein expression of UCP1 and OXPHOS were elevated in differentiated adipocytes treated with PlGF. PlGF stimulated mitochondrion transcription and increased copy number of mitochondrial. When subjected for respirometry, PlGF-treated differentiated adipocytes showed higher oxygen consumption rates than controls. PlGF induced AMPK phosphorylation and blockade of AMPK phosphorylation blunted UCP1 and OXPHOS expression in differentiated adipocytes. PlGF administration reduced cholesterol and triglyceride content in the liver and improved insulin sensitivity in db mice compared with control. In Conclusion, PlGF could activate BAT function. Downregulation of PlGF might contribute to the reduced BAT activity in GDM.
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PMID:Activation of brown adipocytes by placental growth factor. 3019 93

Brown adipose tissue (BAT) is an exclusive tissue of nonshivering thermogenesis. It is fueled by lipids and glucose and involved in energy and metabolic homeostasis. Intrauterine exposure to hyperglycemia during gestational diabetes mellitus may result in abnormal fetal development and metabolic phenotypes in adulthood. However, whether intrauterine hyperglycemia influences the development of BAT is unknown. In this study, mouse embryos were exposed to the intrauterine hyperglycemia environment by injecting streptozocin into pregnant mice at 1 d post coitum (dpc). The structure of BAT was examined by hematoxylin and eosin staining and immunohistochemical analysis. The glucose uptake in BAT was measured in vivo by [18F]-fluoro-2-deoxyglucose-micro-positron emission tomography. The gene expression in BAT was determined by real-time PCR, and the 5'-C-phosphate-G-3' site-specific methylation was quantitatively analyzed. Intrauterine hyperglycemia exposure resulted in the impaired structure of BAT and decreased glucose uptake function in BAT in adulthood. The expressions of the genes involved in thermogenesis and mitochondrial respiratory chain in BAT, such as Ucp1, Cox5b, and Elovl3, were down-regulated by intrauterine hyperglycemia exposure at 18.5 dpc and at 16 wk of age. Furthermore, higher methylation levels of Ucp1, Cox5b, and Elovl3 were found in offspring of mothers with streptozotocin-induced diabetes. Our results provide the evidence for enduring inhibitory effects of intrauterine hyperglycemia on BAT development in offspring. Intrauterine hyperglycemia is associated with increased DNA methylation of the BAT specific genes in offspring, which support an epigenetic involvement.-Yu, D.-Q., Lv, P.-P., Yan, Y.-S., Xu, G.-X., Sadhukhan, A., Dong, S., Shen, Y., Ren, J., Zhang, X.-Y., Feng, C., Huang, Y.-T., Tian, S., Zhou, Y., Cai, Y.-T., Ming, Z.-H., Ding, G.-L., Zhu, H., Sheng, J.-Z., Jin, M., Huang, H.-F. Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue.
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PMID:Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue. 3075 46

Introduction: One-fifth of pregnancies with pre-gestational diabetes mellitus (pre-DM) yield placentas <10th percentile small for gestational age (SGA), compared to a non-diabetic population. We hypothesized that SGA placentas of women with pre-DM, whether type I (T1DM) or type II (T2DM), exhibit distinct histopathological changes and pregnancy outcomes compared to pre-DM pregnancies with an AGA placenta.Methods: We conducted a retrospective, cohort study of placentas from pregnant women enrolled in the Diabetes in Pregnancy Program at Brown University between 2003 and 2011, by comparing pre-DM patients with SGA placentas to pre-DM patients with AGA placental weights.Results: The SGA placenta groups were associated with an increased risk for adverse clinical outcomes, compared to AGA placentas in pregnancies complicated by either T1DM or T2DM. Compared to their AGA pre-DM counterparts, T1DM, SGA placentas show increased peri-villous fibrin/fibrinoid deposition, thrombosis in fetal blood vessels, and meconium staining. Moreover, the histopathology of SGA placentas from T2DM is characterized by decidual vasculopathy, accelerated villous maturity, and erythroblastosis, compared to T2DM AGA placentas. The contrasting placental pathologies between the two pre-DM SGA phenotypes evolved independent of patient demographics and were unrelated to indicators of the glycemic control present at early gestational ages.Discussion: A sub-population of pre-DM women with either T1DM or T2DM diabetes that have an SGA placenta are at increased risk for adverse clinical outcomes in pregnancy, compared to pre-DM women with AGA placental weights.
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PMID:Small-for-gestational age placentas associate with an increased risk of adverse outcomes in pregnancies complicated by either type I or type II pre-gestational diabetes mellitus. 3242 23

Gestational diabetes (GDM) is a common metabolic complication of pregnancy that is generally asymptomatic in its clinical course, although it is potentially associated with a wide range of both maternal and foetal complications. The population prevalence of GDM varies widely, depending on the clinical diagnostic criteria, ethnicity, demographics and background prevalence of type 2 diabetes. Climate variability and environmental temperature have recently come to the forefront as potential direct or indirect determinants of human health. The association between GDM and environmental temperature is complex, and studies have often reported conflicting findings. Epidemiologic studies have shown a direct relation between rising environmental temperature and the risk of both GDM and impaired beta cell function. Seasonal trends in the prevalence of GDM have been reported in several populations, with a higher prevalence in summer months. Multiple mechanisms have been proposed to explain the GDM-temperature correlation. A growing body of evidence supports a link between temperature, energy expenditure and adipose tissue metabolism. Brown adipose tissue thermogenesis, induced by cold temperatures, improves insulin sensitivity. Further biological explanations for the GDM-temperature correlation lie in potential association with low vitamin D levels, which varies according to sunshine exposure. Observational studies are also complicated by lifestyle factors, such as diet and physical activity, that could exhibit seasonal variation. In this review article, we provide a systematic overview of available epidemiological evidence linking environmental temperature and gestational diabetes. Furthermore, the physiological mechanisms that give biological plausibility to association between GDM and temperature are explored. As future climate patterns could drive global changes in GDM prevalence, this knowledge has important implications for both clinicians and researchers.
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PMID:Gestational diabetes, environmental temperature and climate factors - From epidemiological evidence to physiological mechanisms. 3304 75