Fetal origins of obesity: a novel pathway of regulating appetite neurons in the hypothalamus of growth-restricted rat offspring.

PURPOSE: Fetal growth restriction causes a series of sequelae, some of which, such as hyperphagia, reduced satiety and postnatal obesity, are believed to be associated with embryonic hypothalamic neurons impairment. The mechanisms underlying the linkage of fetal brain injuries to break the energy homeostasis have not been elucidated completely. Here, we aim to investigate the effect of intrauterine energy restriction on remodeling appetite neurons in the hypothalamus of fetal and postnatal infant rats. METHODS: Low-protein (8%) diet combined with 75% energy restriction was used to establish an animal model. Rats offspring brain tissues, harvested from embryo day 18 and postnatal infant day 1, were sampled for dependent regulator analyses and master neuron assessment. RESULTS: Growth-restricted rats showed the increased expression of Bsx and NPY in the hypothalamus as well as remodeling hypothalamic neurons differentiation compared to controls. Intriguingly, in cells cultured in vitro test, we found that activated effects of Bsx and NPY could be exacerbated by DNMT1 inhibitor. CONCLUSIONS: In embryonic and early postnatal stage of FGR rats, we detected high concentrations of orexigenic neurons in the hypothalamus. DNMT1 activity is correlated with early embryonic neurogenesis by mediating the expression of Bsx and NPY. It may be one of the reasons for the abnormal development of the appetite regulation pathway and higher susceptibility to obesity in FGR offspring.

One-step synthesis of nitrogen-doped multi-emission carbon dots and their fluorescent sensing in HClO and cellular imaging.

Tunable multicolor carbon dots (CDs) with a quantum yield reach up to 35% were generated directly from rhodamine and urea via one-step hydrothermal approach and purified through silica gel column chromatography. Transmission electron microscopy images reveal that the as-prepared CDs possess a small size distribution below 10 nm with bright blue, green, and yellow color emission, designated as b-CDs, g-CDs, and y-CDs, respectively. The in-depth investigations reveal that the multicolor emission CDs with different fraction displays fluorescence emission wavelength ranges from 398 nm (b-CDs), 525 nm (g-CDs), to 553 nm (y-CDs) which could be well modulated by controlling the amount of heteroatom nitrogen especially amino nitrogen onto their surface structures. Further experiments verify the important role of nitrogen content by using rhodamine solely or substituting urea with sulfur containing compounds as precursors to produce corresponding CDs since the performance is lower than that of urea incorporation. Theoretical calculation results also reveal that the increasing amount of amino nitrogen into their surface structures of b-CDs, g-CDs to y-CDs is responsible for reduced band gaps energy, which result in the redshifted wavelength. Benefiting from the excellent photoluminescence properties, wide pH variation range, high photo stability, and low toxicity, these CDs were employed for HClO sensing at 553 nm within the range 5 to 140 µM with a limit of detection (LOD) of 0.27 ± 0.025 µM (n = 3) and multicolor cellular imaging in HeLa cells. Tunable multicolor carbon dots (CDs) were generated directly from rhodamine and urea via one-step hydrothermal approach and purified through silica gel column chromatography. The as-prepared CDs exhibit bright blue, green, and yellow color emission which could be well modulated by controlling the increasing incorporation of heteroatom nitrogen especially amino nitrogen into their surface structures. These CDs were employed for HClO sensing and demonstrated to multicolor cellular imaging in HeLa cells.

Fas, Caspase-8, and Caspase-9 pathway-mediated bile acid-induced fetal cardiomyocyte apoptosis in intrahepatic cholestasis pregnant rat models.

AIM: Intrahepatic cholestasis of pregnancy (ICP) is a specific complication in the middle and late pregnancy and has been recognized as one of the high-risk pregnancy for sudden fetal death. In this study, we aimed to investigate the role of Fas, Caspase-8, and Caspase-9 pathways in the internal relations of fetal myocardial apoptosis in ICP rat models, thus resulting in fetal intrauterine death. Furthermore, we researched whether ursodeoxycholic acid (UDCA) promoted benefits in fetal cardiomyocyte apoptosis. MATERIALS AND METHODS: To establish ICP rat models, on the 15th day of pregnancy, rats were injected 17α-ethynyl estradiol (EE2). Meanwhile, in experimental group, pregnant rats were treated with EE2 + UDCA. All rats were sacrificed on the 21st day of pregnancy. The expression levels of Fas, Caspase-8, and Caspase-9 were examined by western blot and real-time polymerase chain reaction analysis. Fetal rat cardiac tissues were removed and stained for pathological evaluation. In addition, we observed fetal myocardial structure by using transmission electron microscopy. RESULTS: We detected high concentrations of bile acids and transaminase in the fetal circulation. And we found increased expression levels of Fas, Caspase-8, and Caspase-9 proteins and mRNA in the fetal cardiomyocyte in EE2-treated group but not in control- or EE2 + UDCA-treated groups. Furthermore, compared to controls, EE2-treated rats exhibited severe fetal myocardial structure damage and the apoptotic bodies by using transmission electron microscopy. UDCA reversed the impairment of fetal cardiomyocytes. CONCLUSION: Our study has led to research into the association between activation of Fas, Caspase-8, and Caspase-9 pathways and bile acid-induced fetal cardiomyocyte apoptosis, which may be one of the mechanisms on fetal cardiac death in ICP. More importantly, UDCA may improve the adverse outcome of fetus.

The Interaction of PPARα and CYP7B1 with ERα, ß Impacted the Occurrence and Development of Intrahepatic Cholestasis in Pregnant Rats.

Intrahepatic cholestasis of pregnancy (ICP) is a disorder of bile acid (BA) synthesis, excretion, and metabolism, with systemic accumulation of BAs, which can lead to prematurity, fetal distress, and intrauterine death. Here, we investigate the expression of peroxisome proliferator-activated receptor alpha and cytochrome P450 oxysterol 7alpha-hydroxylase by exposing to 17α-ethynylestradiol with or without the estrogen receptor signaling pathway in pregnant rats with intrahepatic cholestasis. In vivo and in vitro evidences showed that estrogen receptor alpha (ERα) may be the key point of occurrence and development of intrahepatic cholestasis in pregnant rats. Besides, the abnormalities in genes could be reversed by ERα small interfering RNA. Our findings provide the ERα-centered hypothesis on the mechanisms of ICP. New perspectives are emerging for the treatment of estrogen-induced hepatic complication.