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Pancreatic α-cells are important in maintaining metabolic homeostasis, but their role in regulating maternal metabolic adaptations to pregnancy has not been studied. The objective of this study was to determine whether pancreatic α-cells respond to pregnancy and their contribution to maternal metabolic adaptation. With use of C57BL/6 mice, the findings of our study showed that pregnancy induced a significant increase of α-cell mass by promoting α-cell proliferation that was associated with a transitory increase of maternal serum glucagon concentration in early pregnancy. Maternal pancreatic GLP-1 content also was significantly increased during pregnancy. Using the inducible Cre/loxp technique, we ablated the α-cells (α-null) before and during pregnancy while maintaining enteroendocrine L-cells and serum GLP-1 in the normal range. In contrast to an improved glucose tolerance test (GTT) before pregnancy, significantly impaired GTT and remarkably higher serum glucose concentrations in the fed state were observed in α-null dams. Glucagon receptor antagonism treatment, however, did not affect measures of maternal glucose metabolism, indicating a dispensable role of glucagon receptor signaling in maternal glucose homeostasis. However, the GLP-1 receptor agonist improved insulin production and glucose metabolism of α-null dams. Furthermore, GLP-1 receptor antagonist Exendin (9-39) attenuated pregnancy-enhanced insulin secretion and GLP-1 restored glucose-induced insulin secretion of cultured islets from α-null dams. Together, these results demonstrate that α-cells play an essential role in controlling maternal metabolic adaptation to pregnancy by enhancing insulin secretion.

Hypoadiponectinemia is a risk factor of gestational diabetes mellitus (GDM). Our previous study reported that adiponectin gene knockout mice (Adipoq -/- ) develop GDM due to insulin insufficiency. The main objective of this study was to elucidate the underlying mechanism through which adiponectin controls islet expansion during pregnancy. A significant reduction in β-cell proliferation rates, β-cell areas, and blood insulin concentrations was detected in Adipoq -/- mice at midpregnancy. Surprisingly, conditionally knocking down adiponectin receptor 1 (AdipoR1) or AdipoR2 genes in β-cells during pregnancy did not reduce β-cell proliferation rates or blood insulin concentrations. In vitro adiponectin treatment also failed to show any effect on β-cell proliferation of isolated pancreatic islets. It was reported that placental lactogen (PL) plays a crucial role in pregnancy-induced maternal β-cell proliferation. A significant decrease in phosphorylation of signal transducer and activator of transcription 5, a downstream molecule of PL signaling, was observed in islets from Adipoq -/- dams. The mRNA levels of mouse PL genes were robustly decreased in the placentas of Adipoq -/- dams. In contrast, adiponectin treatment increased PL expression in human placenta explants and JEG3 trophoblast cells. Most importantly, bovine PL injection restored β-cell proliferation and blood insulin concentrations in Adipoq -/- dams. Together, these results demonstrate that adiponectin plays a vital role in pregnancy-induced β-cell proliferation by promoting PL expression in trophoblast cells.

To ensure fetal lipid supply, maternal blood triglyceride (TG) concentrations are robustly elevated during pregnancy. Interestingly, a lower increase in maternal blood TG concentrations has been observed in some obese mothers. We have shown that high-fat (HF) feeding during pregnancy significantly reduces maternal blood TG levels. Therefore, we performed this study to investigate if and how obesity alters maternal blood TG levels. Maternal obesity was established by prepregnant HF (ppHF) feeding, which avoided the dietary effect during pregnancy. We found not only that maternal blood TG concentrations in ppHF dams were remarkably lower than in control dams but also that the TG peak occurred earlier during gestation. Hepatic TG production and intestinal TG absorption were unchanged in ppHF dams, but systemic lipoprotein lipase (LPL) activity was increased, suggesting that increased blood TG clearance contributes to the decreased blood TG concentrations in ppHF dams. Although significantly higher levels of UCP1 protein were observed in interscapular brown adipose tissue (iBAT) of ppHF dams, Ucp1 gene deletion did not restore blood TG concentrations in ppHF dams. Expression of the angiopoietin-like protein 4 (ANGPTL4), a potent endogenous LPL inhibitor, was significantly increased during pregnancy. However, the pregnancy-induced elevation of blood TG was almost abolished in Angptl4 -/- dams. Compared with control dams, Angptl4 mRNA levels were significantly lower in iBAT, gonadal white adipose tissue, and livers of ppHF dams. Importantly, ectopic overexpression of ANGPTL4 restored maternal blood TG concentrations in ppHF dams. Together, these results indicate that ANGPTL4 plays a vital role in increasing maternal blood TG concentrations during pregnancy. Obesity impairs the rise of maternal blood TG concentrations by reducing ANGPTL4 expression in mice.

BackgroundExcessive gestational weight gain (EGWG) closely associates with postpartum obesity. However, the causal role of EGWG in postpartum obesity has not been experimentally verified. The objective of this study was to determine whether and how EGWG causes long-term postpartum obesity.MethodsC57BL/6 mice were fed with high-fat diet during gestation (HFFDG) or control chow, then their body composition and energy metabolism were monitored after delivery.ResultsWe found that HFFDG significantly increased gestational weight gain. After delivery, adiposity of HFFDG-treated mice (Preg-HF) quickly recovered to the levels of controls. However, 3 months after parturition, Preg-HF mice started to gain significantly more body fat even with regular chow. The increase of body fat of Preg-HF mice was progressive with aging and by 9 months after delivery had increased 2-fold above the levels of controls. The expansion of white adipose tissue (WAT) of Preg-HF mice was manifested by hyperplasia in visceral fat and hypertrophy in subcutaneous fat. Preg-HF mice developed low energy expenditure and UCP1 expression in interscapular brown adipose tissue (iBAT) in later life. Although blood estrogen concentrations were similar between Preg-HF and control mice, a significant decrease in estrogen receptor α (ERα) expression and hypermethylation of the ERα promoter was detected in the fat of Preg-HF mice 9 months after delivery. Interestingly, hypermethylation of ERα promoter and low ERα expression were only detected in adipocyte progenitor cells in both iBAT and WAT of Preg-HF mice at the end of gestation.ConclusionsThese results demonstrate that HFFDG causes long-term postpartum obesity independent of early postpartum fat retention. This study also suggests that HFFDG adversely programs long-term postpartum energy metabolism by epigenetically reducing estrogen signaling in both BAT and WAT.

The main objective of this study was to investigate the effect of maternal obesity on offspring's glucose metabolism during the perinatal period. Maternal obesity was established by feeding C57BL/6 mice with a high-fat (HF) diet before or during pregnancy. Our results showed that prolonged prepregnant HF feeding but not HF feeding during pregnancy significantly reduced fetal and neonatal blood glucose concentrations. Remarkably, elevated blood insulin concentrations and increased activation of insulin signaling were observed in fetuses and neonates from prepregnant HF-fed dams. In addition, significantly larger β-cell areas were observed in pancreases of fetuses and neonates from prepregnant HF-fed dams. Although there was no significant change in placental cross-sectional area or GLUT 1 expression, prepregnant HF feeding significantly enhanced the expression of genes that control placental fatty acid supply. Interestingly, reducing fatty acid supply to the placenta and fetus by placental-specific knockout of adipose triglyceride lipase not only reduced fetal β-cell area and blood insulin concentration but also attenuated prepregnant HF feeding-induced reduction in offspring blood glucose concentrations during the perinatal period. Together, these results indicate that placental and fetal fatty acid supply plays an important role in fetal β-cell development, insulin secretion, and glucose metabolism. Prolonged prepregnant maternal HF feeding resembles pregravid maternal obesity in mice, which reduces fetal and neonatal blood glucose concentrations by enhancing fetal β-cell development and insulin secretion.

BackgroundNumerous pathologies of pregnancy originate from placental dysfunction. It is essential to understand the functions of key genes in the placenta in order to discern the etiology of placental pathologies. A paucity of animal models that allow conditional and inducible expression of a target gene in the placenta is a major limitation for studying placental development and function.ResultsTo study the platelet-derived growth factor receptor alpha (PDGFRα)-directed and tamoxifen-induced Cre recombinase expression in the placenta, PDGFRα-CreER mice were crossed with mT/mG dual-fluorescent reporter mice. The expression of endogenous membrane-localized enhanced green fluorescent protein (mEGFP) and/or dTomato in the placenta was examined to identify PDGFRα promoter-directed Cre expression. Pregnant PDGFRα-CreER;mT/mG mice were treated with tamoxifen at various gestational ages. Upon tamoxifen treatment, reporter protein mEGFP was observed in the junctional zone (JZ) and chorionic plate (CP). Furthermore, a single dose of tamoxifen was sufficient to induce the recombination.ConclusionsPDGFRα-CreER expression is restricted to the JZ and CP of mouse placentas. PDGFRα-CreER mice provide a useful tool to conditionally knock out or overexpress a target gene in these regions of the mouse placenta.

Sizes and number concentrations are critical parameters for the impact of atmospheric particles on climate and human health. However, comprehensive studies focusing on size‐resolved particle number (PN) emissions from various sectors are scarce. This study aims to fill this research gap by developing sectoral size‐resolved PN emissions for major species including sulfate, organic mass (OM), and black carbon (BC). The size‐resolved emission profiles derived from various measurements in the literature were integrated with a particle mass emission inventory (EI) for 13 major sectors in the Yangtze River Delta region of China as a case study. The particle number size distribution (PNSD) of emitted particles exhibited two distinct peaks: one at approximately 10 nm and the other in the range of 40–60 nm. The primary contributors to PN emissions in the region in 2017 were power plants, gasoline vehicles, diesel vehicles, and cooking sources. In terms of species, OM dominated PN emissions, followed by primary sulfate and then BC. A regional size‐resolved aerosol model employing the size‐resolved PN EI developed here (referred to as the BIN‐SPE experiment) provided reasonably accurate temporal variations of the total PN concentration and captured the PNSD within the size range of 10–300 nm. Uncertainty analysis of sectoral PN emissions across size ranges was carried out and the performance of the BIN‐SPE experiment was compared with those of three commonly used PN emission parameterizations. Our model evaluations highlight future needs for in‐depth investigations into more advanced size‐resolved emissions and secondary OM formation mechanisms. Plain Language Summary: Various sources such as power plants, vehicles, cooking, and others emit numerous small particles. Quantifying their sizes and number emissions is crucial for understanding atmospheric particle number size distribution and its impacts on climate and health. However, few studies comprehensively address sectoral size‐resolved particle number emissions, with most focusing on global scales or single source. This study couples size‐resolved emission profiles reported in literature for 13 major sectors with mass emission inventories to quantify sectoral size‐resolved particle number emissions with speciation for the Yangtze River Delta region in China. The particle number emissions exhibit a bimodal distribution with peaks at approximately 10 and 40–60 nm. Primary contributors are power plants, gasoline vehicles, diesel vehicles, and cooking sources. In terms of species, organic matter dominates particle number emissions, followed by primary sulfate and black carbon. Notably, the peak in emissions with sizes less than 20 nm reconciles the disparity between modeled and observed distributions. To the best of our knowledge, this study represents the first comprehensive examination of sectoral particle number emissions with speciation in China. The method and data sets utilized in this study can be employed to quantify particle number emissions in other regions and are instrumental for impact assessments. Key Points: An emission profile‐based method is applied to quantify sectoral size‐resolved particle number emissions with speciationVehicles, power plants, and cooking dominate bimodal particle number emissions, with organics and primary sulfate as major speciesProminent particle number emissions with sizes less than 20 nm substantially reduce model‐observation disparities [ABSTRACT FROM AUTHOR]

Hypoadiponectinemia has been widely observed in patients with gestational diabetes mellitus (GDM). To investigate the causal role of hypoadiponectinemia in GDM, adiponectin gene knockout (Adipoq-/- ) and wild-type (WT) mice were crossed to produce pregnant mouse models with or without adiponectin deficiency. Adenoviral vector-mediated in vivo transduction was used to reconstitute adiponectin during late pregnancy. Results showed that Adipoq-/- dams developed glucose intolerance and hyperlipidemia in late pregnancy. Increased fetal body weight was detected in Adipoq-/- dams. Adiponectin reconstitution abolished these metabolic defects in Adipoq-/- dams. Hepatic glucose and triglyceride production rates of Adipoq-/- dams were significantly higher than those of WT dams. Robustly enhanced lipolysis was found in gonadal fat of Adipoq-/- dams. Interestingly, similar levels of insulin-induced glucose disposal and insulin signaling in metabolically active tissues in Adipoq-/- and WT dams indicated that maternal adiponectin deficiency does not reduce insulin sensitivity. However, remarkably decreased serum insulin concentrations were observed in Adipoq-/- dams. Furthermore, β-cell mass, but not glucose-stimulated insulin release, in Adipoq-/- dams was significantly reduced compared with WT dams. Together, these results demonstrate that adiponectin plays an important role in controlling maternal metabolic adaptation to pregnancy.

Many cities in China are facing the dual challenge of PM2.5 and PM10 pollution. There is an urgent need to develop a cost-effective method that can apportion both with high-time resolution. A novel and practical apportionment method is presented in this study. It combines the measurement of particle mass size distribution (PMSD) with an optical particle counter (OPC) and the algorithm of normalized non-negative matrix factorization (N-NMF). Applied in the city center of Baoding, Hebei, this method separates four distinct pollution factors. Their sizes (ordered from the smallest to largest) range from 0.16 μm to 0.6 μm, 0.16 μm to 1.0 μm, 0.5 μm to 17.0 μm, and 2.0 μm to 20.0 μm, respectively. They correspondingly contribute to PM2.5 (PM10) with portions of 26% (17%), 37% (26%), 33% (41%), and 4% (16%), respectively, on average. The smaller three factors are identified as combustion, secondary, and industrial aerosols because of their high correlation with carbonaceous aerosols, nitrate aerosols, and trace elements of Fe/Mn/Ca in PM2.5, respectively. The largest-sized factor is linked to dust aerosols. The primary origin regions, oxidation degrees, and formation mechanisms of each source are further discussed. This provides a scientific basis for the comprehensive management of PM2.5 and PM10 pollution. [ABSTRACT FROM AUTHOR]

The geogrid flexible reinforced soil wall is widely used in engineering practice. However, a more comprehensive understanding of the dynamic behavior of reinforced soil wall is still required for a more reasonable application. In order to explore the mechanical behavior of a geogrid flexible reinforced soil wall, the model test was carried out to investigate the dynamic deformation of geogrid reinforced soil wall subjected to a repeated load. The numerical simulation was also conducted for comparison and extension with regards to the earth pressure and the reinforcement strain. The change rules for the deformation of the wall face, the vertical earth pressure and the reinforcement strain subjected to dynamic load with four frequencies (4, 6, 8 and 10 Hz) and four amplitudes (30–60, 40–80, 50–100 and 60–120 kPa) were obtained. The factors that affect the mechanical behavior of geogrid flexible reinforced soil wall were analyzed. The results show that the dynamic deformation characteristics of reinforced soil wall are affected by the number of vibrations, the amplitude of dynamic load and the frequency of vibration. The maximum lateral displacement of the reinforced soil wall occurs on the third to the fifth layer. With an increase in dynamic load amplitude, the development of dynamic deformation gradually increases, and after a cumulative vibration of 200 × 104 times, the cumulative lateral deformation ratio and the cumulative vertical deformation ratio of the wall face is less than 1%. The vertical earth pressure of geogrid flexible reinforced soil wall increases partially along the length of the reinforcement, and the vertical earth pressure of the third layer is basically unchanged when subjected to a dynamic load. With an increase in vibration number, the change in the reinforcement strain of the third layer is more complex, and the change rules of the reinforcement strain of each layer are different. The reinforcement strain is small, with a maximum value of 0.1%. [ABSTRACT FROM AUTHOR]