ORCID Profile
0000-0002-7232-072X
Current Organisation
Washington State University
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: American Physiological Society
Date: 12-2010
DOI: 10.1152/AJPENDO.00434.2010
Abstract: Maternal obesity (MO) has harmful effects on both fetal development and subsequent offspring health. The impact of MO on fetal myocardium development has received little attention. Fibrogenesis is regulated by the transforming growth factor-β (TGF-β) 38 signaling pathway. Using the well-established model of MO in pregnant sheep, we evaluated the effect of MO on TGF-β 38 and collagen accumulation in fetal myocardium. Nonpregnant ewes were assigned to a control diet [Con, fed 100% of National Research Council (NRC) nutrient recommendations] or obesogenic diet (OB, fed 150% of NRC recommendations) from 60 days before conception. Fetal ventricular muscle was s led at 75 and 135 days of gestation (dG). At 75 dG, the expression of precursor TGF-β was 39.9 ± 9.9% higher ( P 0.05) in OB than Con fetal myocardium, consistent with the higher content of phosphorylated Smad3 in OB myocardium. The phosphorylation of p38 tended to be higher in OB myocardium ( P = 0.08). In addition, enhanced Smad complexes were bound to Smad-binding elements in 75 dG OB fetal myocardium measured by DNA mobility shift assay (130.2 ± 26.0% higher, P 0.05). Similar elevation of TGF-β signaling was observed in OB fetal myocardium at 135 dG. Total collagen concentration in OB was greater than Con fetal myocardium (2.42 ± 0.16 vs. 1.87 ± 0.04%, P 0.05). Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 were higher in the Con group compared with OB sheep (43.86 ± 16.01 and 37.23 ± 7.97% respectively, P 0.05). In summary, MO results in greater fetal heart connective tissue accumulation associated with an upregulated TGF-β 38 signaling pathway at late gestation such changes would be expected to negatively impact offspring heart function.
Publisher: American Physiological Society
Date: 04-2009
DOI: 10.1152/AJPENDO.90924.2008
Abstract: Skeletal muscle is one of the primary tissues responsible for insulin resistance and type 2 diabetes (T2D). The fetal stage is crucial for skeletal muscle development. Obesity induces inflammatory responses, which might regulate myogenesis through Wnt/β-catenin signaling. This study evaluated the effects of maternal obesity ( % increase in body mass index) during pregnancy on myogenesis and the Wnt/β-catenin and IKK/NF-κB pathways in fetal skeletal muscle using an obese pregnant sheep model. Nonpregnant ewes were assigned to a control group (C fed 100% of National Research Council recommendations n = 5) or obesogenic (OB fed 150% of National Research Council recommendations n = 5) diet from 60 days before to 75 days after conception (term ∼148 days) when fetal semitendenosus skeletal muscle was s led for analyses. Myogenic markers including MyoD, myogenin, and desmin contents were reduced in OB compared with C fetal semitendenosus, indicating the downregulation of myogenesis. The diameter of primary muscle fibers was smaller in OB fetal muscle. Phosphorylation of GSK3β was reduced in OB compared with C fetal semitendenosus. Although the β-catenin level was lower in OB than C fetal muscle, more β-catenin was associated with FOXO3a in the OB fetuses. Moreover, we found phosphorylation levels of IKKβ and RelA 65 were both increased in OB fetal muscle. In conclusion, our data showed that myogenesis and the Wnt/β-catenin signaling pathway were downregulated, which might be due to the upregulation of inflammatory IKK/NF-κB signaling pathways in fetal muscle of obese mothers.
Publisher: Springer Science and Business Media LLC
Date: 22-05-2012
DOI: 10.1038/IJO.2012.69
Publisher: Wiley
Date: 10-2009
DOI: 10.1002/JCB.22272
Abstract: Two muscle-specific ubiquitin ligases (UL), muscle atrophy F box (MAFbx) and muscle RING finger 1 (MuRF1), are crucial for myofibrillar protein breakdown. The insulin like growth factor-1 (IGF-1) pathway inhibits muscle UL expression through Akt-mediated inhibition of FoxO transcription factors, while AMP-activated protein kinase (AMPK) promotes UL expression. The underlying cellular mechanism, however, remains obscure. In this study, the effect of AMPK and its interaction with IGF-1 on ubiquitin ligases expression was investigated. C2C12 myotubes were treated with 0, 0.1, 0.3, and 1.0 mM 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) in the presence or absence of 50 ng/ml IGF-1. IGF-1 activated Akt, which enhanced phosphorlytion of FoxO3a at Thr 318/321 and reduced the expression of UL. Intriguingly, though activation of AMPK by 0.3 and 1.0 mM AICAR synergized IGF-1-induced Akt activation, the expression of UL was not attenuated, but strengthened by AMPK activation. AICAR treatment decreased FoxO3a phosphorylation at 318/321 in the cytoplasm and induced FoxO3 nuclear relocation. mTOR inhibition increased basal MAFbx expression and reversed the inhibitory effect of IGF-1 on UL expression. In conclusion, our data show that AMPK activation by AICAR stimulates UL expression despite the activation of Akt signaling, which may be due to the possible antagonistic effect of FoxO phosphorylation by AMPK on phosphorylation by Akt. In addition, AMPK inhibition of mTOR may provide an additional explanation for the enhancement of UL expression by AMPK.
Publisher: Bioscientifica
Date: 07-2014
DOI: 10.1530/REP-13-0614
Abstract: Accompanying the dramatic increase in maternal obesity, the incidence of type 1 diabetes (T1D) in children is also rapidly increasing. The objective of this study was to explore the effects of maternal obesity on the incidence of T1D in offspring using non-obese diabetic (NOD) mice, a common model for TID. Four-week-old female NOD mice were fed either a control diet (10% energy from fat, CON) or a high-fat diet (60% energy from fat) for 8 weeks before mating. Mice were maintained in their respective diets during pregnancy and lactation. All offspring mice were fed the CON to 16 weeks. Female offspring (16-week-old) born to obese dams showed more severe islet lymphocyte infiltration (major manifestation of insulitis) ( P .01), concomitant with elevated nuclear factor kappa-light-chain-enhancer of activated B cells p65 signaling ( P .01) and tumor necrosis factor alpha protein level ( P .05) in the pancreas. In addition, maternal obesity resulted in impaired ( P .05) glucose tolerance and lower ( P .05) serum insulin levels in offspring. In conclusion, maternal obesity resulted in exacerbated insulitis and inflammation in the pancreas of NOD offspring mice, providing a possible explanation for the increased incidence of T1D in children.
Publisher: Oxford University Press (OUP)
Date: 2012
Abstract: Many areas of the western United States have soils that have increased Se content, and ruminants grazing these rangelands may ingest increased quantities of Se. In addition, high-energy diets or increased Se intake may induce gut inflammation. The objective of this study was to evaluate the effects of maternal plane of nutrition and increased dietary Se during gestation on inflammatory responses in neonatal lamb ileal tissue, a major immune organ. Rambouillet ewes (age = 240 ± 17 d initial BW = 52.1 ± 6.2 kg) were allocated to 4 treatments arranged in a 2 × 2 factorial. Factors included Se [adequate Se (ASe, 11.5 µg/kg of BW) or high Se (HSe, 77.0 µg/kg of BW)] initiated at breeding, and nutritional plane [100% (CON) or 140% (HIH) of requirements] initiated at d 40 of gestation. Ewes were fed in idually from d 40, and lambs were removed at parturition and fed artificial colostrum and milk replacer. Lambs were necropsied at 20 d of age, and ileal tissues were s led for immunoblotting and real-time quantitative reverse-transcription PCR analyses. The ASe-HIH and HSe-CON treatments had no effect (P = 0.179) on inflammatory signaling compared with ASe-CON. However, greater inflammatory signaling was detected in the HSe-HIH group, as shown by increased (P < 0.05) mRNA expression of tumor necrosis factor-α and chemotaxis IL-8. Consistently, phosphorylation of c-Jun N-terminal kinase, a primary inflammatory signaling mediator, was greater (P < 0.05) in the HSe-HIH group compared with other treatments. Consistent with cytokine expression, mast cell density was less in the HSe-CON group than in other treatments. The expression of transforming growth factor β mRNA was greater (P < 0.05) in the HSe-HIH group consistently, collagen content was increased in the HSe-HIH group compared with the ASe-CON group (P < 0.05). In conclusion, independently, neither HSe nor HIH had major effects on inflammation, but in combination, these maternal treatments induced an inflammatory response in the neonatal intestine.
Publisher: Public Library of Science (PLoS)
Date: 14-02-2012
Publisher: CRC Press
Date: 15-10-2015
DOI: 10.1201/B19250
Publisher: Oxford University Press (OUP)
Date: 07-2011
DOI: 10.1002/IBD.21539
Publisher: Oxford University Press (OUP)
Date: 02-2011
Publisher: The Endocrine Society
Date: 2010
DOI: 10.1210/EN.2009-0849
Abstract: Maternal obesity is increasing at an alarming rate. We previously showed that maternal obesity induces an inflammatory response and enhances adipogenesis in fetal skeletal muscle at midgestation. The objective of this study was to evaluate effects of maternal obesity on adipogenesis, inflammatory signaling, and insulin pathways at late gestation when ovine fetal skeletal muscle matures. Nonpregnant ewes were assigned to a control diet (Con, fed 100% of National Research Council nutrient recommendations, n = 6) or obesogenic diet (OB, fed 150% of National Research Council recommendations, n = 6) from 60 d before to 135 d after conception (term 148 d) when the fetal semitendenosus skeletal muscle was s led. Expression of the adipogenic marker, peroxisome proliferator-activated receptor-γ, was increased in OB compared with Con fetal semitendenosus muscle, indicating up-regulation of adipogenesis. More intramuscular adipocytes were observed in OB muscle. Phosphorylation of inhibitor-κB kinase-α/β and nuclear factor-κB RelA 65 were both increased in OB fetal muscle, indicating activation of nuclear factor-κB pathway. Phosphorylation of c-Jun N-terminal kinase and c-Jun (at Ser 63 and Ser 73) was also elevated. Toll-like receptor 4 expression was higher in OB than Con fetal muscle. Moreover, despite higher insulin concentrations in OB vs. Con fetal plasma (2.89 ± 0.53 vs. 1.06 ± 0.52 ng/ml P & 0.05), phosphorylation of protein kinase B at Ser 473 was reduced, indicating insulin resistance. In conclusion, our data show maternal obesity-induced inflammatory signaling in late gestation fetal muscle, which correlates with increased im adipogenesis and insulin resistance, which may predispose offspring to later-life obesity and diabetes.
Publisher: Oxford University Press (OUP)
Date: 04-2010
Abstract: The Rendement Napole (RN) genotype widely exists in H shire pigs. Recently, RN gene was identified as a R200Q mutation in AMP-activated protein kinase (AMPK) gamma3 subunit. The effect of RN genotype on the growth performance of animals and the underlying mechanisms remain controversial. Using transgenic mice carrying an analogous R225Q mutation, the objective of this study was to study the role of RN gene in the growth performance of animals at different energy levels. Wild-type (WT) mice and those with the RN mutation were assigned to 4 groups: 1) WT plus normal diet, 2) RN plus normal diet, 3) WT plus high-energy diet, and 4) RN plus high-energy diet. Mice were weaned at 21 d old and fed the trial diets for 1 mo and then killed for carcass measurements. The pH of postmortem muscle from RN mice was less (P < 0.01) than that from WT mice. No difference in growth performance was observed when mice were fed a normal diet. When fed a high-energy diet, RN mice showed a greater fat accumulation (WT vs. RN, 1.11 vs. 1.63 g for gonadal fat and 1.40 vs. 1.84 g for subcutaneous fat P < 0.05). Muscle weight was also increased (WT vs. RN, 0.27 vs. 0.30 g for gastrocnemius muscle P < 0.05). The food consumption was greater in RN compared with WT mice (2.95 vs. 2.49 g P < 0.05). The AMPK content and its downstream target, acetyl-CoA carboxylase (ACC), content were greater in RN mice (P < 0.05). The phosphorylation of ACC at Ser 79, a site exclusively phosphorylated by AMPK, was increased (P < 0.05), showing greater AMPK activity in RN mouse muscle. No difference in muscle fiber composition and mitochondrial content was observed between WT and RN mice. High fat diet downregulates protein kinase B but upregulates extracellular signal-regulated kinase signaling. In conclusion, the R225Q mutation has no major effect on the growth performance of animals fed a normal diet a high-energy diet increased fatness in RN mice, likely due to their greater consumption of feed compared with WT mice.
Publisher: PeerJ
Date: 04-12-2017
DOI: 10.7717/PEERJ.4107
Abstract: Integrating genomic information into cattle breeding is an important approach to exploring genotype-phenotype relationships for complex traits related to diary and meat production. To assist with genomic-based selection, a reference map of interactome is needed to fully understand and identify the functional relevant genes. To this end, we constructed a co-expression analysis of 92 tissues and this represents the systematic exploration of gene-gene relationship in Bos taurus . By using robust WGCNA (Weighted Gene Correlation Network Analysis), we described the gene co-expression network of 5,000 protein-coding genes with majority variations in expression across 92 tissues. Further module identifications found 55 highly organized functional clusters representing erse cellular activities. To demonstrate the re-use of our interaction for functional genomics analysis, we extracted a sub-network associated with DNA binding genes in Bos taurus . The subnetwork was enriched within regulation of transcription from RNA polymerase II promoter representing central cellular functions. In addition, we identified 28 novel linker genes associated with more than 100 DNA binding genes. Our WGCNA-based co-expression network reconstruction will be a valuable resource for exploring the molecular mechanisms of incompletely characterized proteins and for elucidating larger-scale patterns of functional modulization in the Bos taurus genome.
Publisher: Wiley
Date: 05-2008
Publisher: Springer Science and Business Media LLC
Date: 16-05-2011
DOI: 10.1038/NUTD.2011.3
Publisher: American Physiological Society
Date: 06-2010
DOI: 10.1152/AJPENDO.00015.2010
Abstract: Maternal obesity (MO) is increasing at an alarming rate. The objective of this study was to evaluate the effect of MO on fibrogenesis in fetal skeletal muscle during maturation in late gestation. Nonpregnant ewes were assigned to a control diet (Con fed 100% of NRC nutrient recommendations, n = 6) or obesogenic diet (OB fed 150% of NRC recommendations, n = 6) from 60 days before conception, and fetal semitendenosus (St) muscle was s led at 135 days of gestation (term 148 days). Total concentration and area of collagen in cross-sections of muscle increased by 27.0 ± 6.0 ( P 0.05) and 105.1 ± 5.9% ( P = 0.05) in OB compared with Con fetuses. The expression of precursor TGF-β was 177.3 ± 47.6% higher, and concentration of phospho-p38 74.7 ± 23.6% was higher ( P 0.05) in OB than in CON fetal muscle. Increases of 327.9 ± 168.0 ( P 0.05) and 188.9 ± 82.1% ( P 0.05), respectively, were observed for mRNA expression of Smad7 and fibronectin in OB compared with Con muscles. In addition, enzymes involved in collagen synthesis, including lysyl oxidase, lysyl hydroxylase 2b, and prolyl 4-hydroxylase-α1, were increased by 350.2 ± 90.0 ( P 0.05), 236.5 ± 25.2 ( P 0.05), and 82.0 ± 36.2% ( P = 0.05), respectively, in OB muscle. In conclusion, MO-enhanced fibrogenesis in fetal muscle in late gestation was associated with upregulation of the TGF-β 38 signaling pathway. Enhanced fibrogenesis at such an early stage of development is expected to negatively affect the properties of offspring muscle because muscle fibrosis is a hallmark of aging.
Publisher: Oxford University Press (OUP)
Date: 2010
Publisher: Oxford University Press (OUP)
Date: 07-2011
No related grants have been discovered for Min Du.