Placental mitochondrial function, nutrient transporters, metabolic signalling and steroid metabolism relate to fetal size and sex in mice

Fetal growth depends on placental function, which requires energy supplied by mitochondria. Here we investigated whether mitochondrial function in the placenta relates to growth of the lightest and heaviest fetuses of each sex within the litter of mice. Placentas from the lightest and heaviest fetuses were taken to evaluate placenta morphology (stereology), mitochondrial energetics (high-resolution respirometry), and mitochondrial regulators, nutrient transporters, hormone handling and signalling pathways (qPCR and western blotting). We found that mitochondrial complex I and II oxygen consumption rate was greater for placentas supporting the lightest female fetuses, although placental complex I abundance of the lightest females and complexes III and V of the lightest males were decreased compared to their heaviest counterparts. Expression of mitochondrial biogenesis (Nrf1) and fission (Drp1 and Fis1) genes was lower in the placenta from the lightest females, whilst biogenesis-related gene Tfam was greater in the placenta of the lightest male fetuses. Additionally, placental morphology and steroidogenic gene (Cyp17a1 and Cyp11a1) expression were aberrant for the lightest females, but glucose transporter (Glut1) expression lower in only the lightest males versus their heaviest counterparts. Differences in intra-litter placental phenotype were related to sex-dependent changes in the expression of hormone responsive (androgen receptor) and metabolic signalling pathways (AMPK, AKT, PPARγ). Thus, in normal mouse pregnancy, placental structure, function and mitochondrial phenotype are differentially responsive to growth of the female and the male fetus. This study may inform the design of sex-specific therapies for placental insufficiency and fetal growth abnormalities with life-long benefits for the offspring.

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LncRNA HOTAIR regulates glucose transporter Glut1 expression and glucose uptake in macrophages during inflammation

Scientific Reports ◽

10.1038/s41598-020-80291-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Monira Obaid ◽

S. M. Nashir Udden ◽

Prasanna Alluri ◽

Subhrangsu S. Mandal

Keyword(s):

Immune Response ◽

Glucose Metabolism ◽

Glucose Uptake ◽

Immune Cells ◽

Glucose Transporter ◽

Energy Needs ◽

Glut1 Expression ◽

Lncrna Hotair ◽

Upstream Regulators ◽

Glucose Transporter Glut1

AbstractInflammation plays central roles in the immune response. Inflammatory response normally requires higher energy and therefore is associated with glucose metabolism. Our recent study demonstrates that lncRNA HOTAIR plays key roles in NF-kB activation, cytokine expression, and inflammation. Here, we investigated if HOTAIR plays any role in the regulation of glucose metabolism in immune cells during inflammation. Our results demonstrate that LPS-induced inflammation induces the expression of glucose transporter isoform 1 (Glut1) which controls the glucose uptake in macrophages. LPS-induced Glut1 expression is regulated via NF-kB activation. Importantly, siRNA-mediated knockdown of HOTAIR suppressed the LPS-induced expression of Glut1 suggesting key roles of HOTAIR in LPS-induced Glut1 expression in macrophage. HOTAIR induces NF-kB activation, which in turn increases Glut1 expression in response to LPS. We also found that HOTAIR regulates glucose uptake in macrophages during LPS-induced inflammation and its knockdown decreases LPS-induced increased glucose uptake. HOTAIR also regulates other upstream regulators of glucose metabolism such as PTEN and HIF1α, suggesting its multimodal functions in glucose metabolism. Overall, our study demonstrated that lncRNA HOTAIR plays key roles in LPS-induced Glut1 expression and glucose uptake by activating NF-kB and hence HOTAIR regulates metabolic programming in immune cells potentially to meet the energy needs during the immune response.

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Glucose Transporter (Glut1) Expression by Canine Brain Microvessel Endothelial Cells in Culture: An Immunocytochemical Study

Frontiers in Cerebral Vascular Biology - Advances in Experimental Medicine and Biology ◽

10.1007/978-1-4615-2920-0_3 ◽

1993 ◽

pp. 13-18 ◽

Cited By ~ 3

Author(s):

Jay M. Hemmila ◽

Lester R. Drewes

Keyword(s):

Endothelial Cells ◽

Glucose Transporter ◽

Immunocytochemical Study ◽

Cells In Culture ◽

Canine Brain ◽

Glut1 Expression ◽

Microvessel Endothelial Cells ◽

Brain Microvessel ◽

Glucose Transporter Glut1 ◽

Transporter Glut1

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The regulation of glucose transporter (GLUT1) expression by the RNA binding protein HuR

Journal of Cellular Biochemistry ◽

10.1002/jcb.20950 ◽

2006 ◽

Vol 99 (2) ◽

pp. 565-574 ◽

Cited By ~ 21

Author(s):

Kira R. Gantt ◽

Joy Cherry ◽

Melissa Richardson ◽

Vesna Karschner ◽

Ulus Atasoy ◽

...

Keyword(s):

Glucose Transporter ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Glut1 Expression ◽

Glucose Transporter Glut1 ◽

Transporter Glut1

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Metallothionein-I- and -II-deficient mice display increased susceptibility to cadmium-induced fetal growth restriction

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00157.2013 ◽

2013 ◽

Vol 305 (6) ◽

pp. E727-E735 ◽

Cited By ~ 16

Author(s):

Johanna Selvaratnam ◽

Haiyan Guan ◽

James Koropatnick ◽

Kaiping Yang

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Structural Changes ◽

Molecular Mechanisms ◽

Glucose Transporter ◽

Cadmium Exposure ◽

Growth Restriction ◽

Glut1 Expression ◽

Pregnant Mice ◽

Underlying Mechanisms

Maternal cadmium exposure induces fetal growth restriction (FGR), but the underlying mechanisms remain largely unknown. The placenta is the main organ known to protect the fetus from environmental toxins such as cadmium. In this study, we examine the role of the two key placental factors in cadmium-induced FGR. The first is placental enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is known to protect the fetus from exposure to high cortisol levels and subsequently FGR, and the second the cadmium binding/sequestering proteins metallotheionein (MT)-I and -II. Using the MT-I/II −/− mouse model, pregnant mice were administered cadmium, following which pups and placentas were collected and examined. MT-I/II−/− pups exposed to cadmium were significantly growth restricted, but neither placental weight nor 11β-HSD2 was altered. Although cadmium administration did not result in any visible structural changes in the placenta, increased apoptosis was detected in MT-I/II−/− placentas following cadmium exposure, with a significant increase in levels of both p53 and caspase 3 proteins. Additionally, glucose transporter (GLUT1) was significantly reduced in MT-I/II−/− placentas of pups exposed to cadmium, whereas zinc transporter (ZnT-1) remained unaltered. Taken together, these results demonstrate that MT-I/II−/− mice are more vulnerable to cadmium-induced FGR. The present data also suggest that increased apoptosis and reduced GLUT1 expression in the placenta contribute to the molecular mechanisms underlying cadmium-induced FGR.

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Glucose transporter GLUT1 expression and clinical outcome in solid tumors: a systematic review and meta-analysis

Oncotarget ◽

10.18632/oncotarget.15171 ◽

2017 ◽

Vol 8 (10) ◽

pp. 16875-16886 ◽

Cited By ~ 63

Author(s):

Ji Wang ◽

Chenyang Ye ◽

Cong Chen ◽

Hanchu Xiong ◽

Binbin Xie ◽

...

Keyword(s):

Systematic Review ◽

Clinical Outcome ◽

Solid Tumors ◽

Glucose Transporter ◽

Meta Analysis ◽

Glut1 Expression ◽

Glucose Transporter Glut1 ◽

Transporter Glut1

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Placental Glucose Transporter GLUT1 Expression in Pre-eclampsia

Placenta ◽

10.1016/j.placenta.2013.06.262 ◽

2013 ◽

Vol 34 (9) ◽

pp. A88

Author(s):

Camilla Marini ◽

Benjamin P. Lüscher ◽

Daniel V. Surbek ◽

Marianne Messerli ◽

Ruth Sager ◽

...

Keyword(s):

Glucose Transporter ◽

Glut1 Expression ◽

Glucose Transporter Glut1 ◽

Transporter Glut1

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Ectopic expression of Hel-N1, an RNA-binding protein, increases glucose transporter (GLUT1) expression in 3T3-L1 adipocytes.

Molecular and Cellular Biology ◽

10.1128/mcb.17.2.954 ◽

1997 ◽

Vol 17 (2) ◽

pp. 954-962 ◽

Cited By ~ 121

Author(s):

R G Jain ◽

L G Andrews ◽

K M McGowan ◽

P H Pekala ◽

J D Keene

Keyword(s):

Glucose Transporter ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Ectopic Expression ◽

Mrna Stabilization ◽

Glut1 Expression ◽

Glucose Transporter Glut1 ◽

Transporter Glut1

3T3-L1 preadipocytes ectopically expressing the mammalian RNA-binding protein Hel-N1 expressed up to 10-fold more glucose transporter (GLUT1) protein and exhibited elevated rates of basal glucose uptake. Hel-N1 is a member of the ELAV-like family of proteins associated with the induction and maintenance of differentiation in various species. ELAV proteins are known to bind in vitro to short stretches of uridylates in the 3' untranslated regions (3'UTRs) of unstable mRNAs encoding growth-regulatory proteins involved in transcription and signal transduction. GLUT1 mRNA also contains a large 3'UTR with a U-rich region that binds specifically to Hel-N1 in vitro. Analysis of the altered GLUT1 expression at the translational and posttranscriptional levels suggested a mechanism involving both mRNA stabilization and accelerated formation of translation initiation complexes. These findings are consistent with the hypothesis that the Hel-N1 family of proteins modulate gene expression at the level of mRNA in the cytoplasm.

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