Abstract:
:cAMP-response element-binding protein (CREB) is required for the induction of adipogenic transcription factors such as CCAAT/enhancer-binding proteins (C/EBPs). Interestingly, it is known from studies in other tissues that LKB1 and its substrates AMP-activated protein kinase (AMPK) and salt-inducible kinases (SIKs) negatively regulate gene expression by phosphorylating the CREB co-activator CRTC2 and class IIa histone deacetylases (HDACs), which results in their exclusion from the nucleus where they co-activate or inhibit their targets. In this study, we show that AMPK/SIK signalling is acutely attenuated during adipogenic differentiation of 3T3-L1 preadipocytes, which coincides with the dephosphorylation and nuclear translocation of CRTC2 and HDAC4. When subjected to differentiation, 3T3-L1 preadipocytes in which the expression of LKB1 was stably reduced using shRNA (Lkb1-shRNA), as well as Lkb1-knockout mouse embryonic fibroblasts (Lkb1(-/-) MEFs), differentiated more readily into adipocyte-like cells and accumulated more triglycerides compared with scrambled-shRNA-expressing 3T3-L1 cells or Wt MEFs. In addition, the phosphorylation of CRTC2 and HDAC4 was reduced, and the mRNA expression of adipogenic transcription factors Cebpa, peroxisome proliferator-activated receptor γ (Pparg) and adipocyte-specific proteins such as hormone-sensitive lipase (HSL), fatty acid synthase (FAS), aP2, GLUT4 and adiponectin was increased in the absence of LKB1. The mRNA and protein expression of Ddit3/CHOP10, a dominant-negative member of the C/EBP family, was reduced in Lkb1-shRNA-expressing cells, providing a potential mechanism for the up-regulation of Pparg and Cebpa expression. These results support the hypothesis that LKB1 signalling keeps preadipocytes in their non-differentiated form.
journal_name
J Mol Endocrinoljournal_title
Journal of molecular endocrinologyauthors
Gormand A,Berggreen C,Amar L,Henriksson E,Lund I,Albinsson S,Göransson Odoi
10.1530/JME-13-0296subject
Has Abstractpub_date
2014-08-01 00:00:00pages
117-30issue
1eissn
0952-5041issn
1479-6813pii
JME-13-0296journal_volume
53pub_type
杂志文章abstract::Human 3beta-hydroxysteroid dehydrogenase/steroid Delta(5)-Delta(4)-isomerase (3beta-HSD/isomerase) is a bifunctional, single enzyme protein that is membrane-bound in the endoplasmic reticulum (microsomes) and mitochondria of cells in the placenta (type I) and in the adrenals and gonads (type II). Two membrane-binding ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0230231
更新日期:1999-10-01 00:00:00
abstract::We investigated the mechanisms by which corticosteroids regulate the expression of the mineralocorticoid receptor (MR) in neurones. Aldosterone and dexamethasone produced a dose-dependent increase of MR and mRNA levels in cultured primary hippocampal neurones. Transient transfection of neuroblastoma cells showed that ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0140285
更新日期:1995-06-01 00:00:00
abstract::The interaction between human papillomaviruses (HPV) and the apolipoprotein-B mRNA-editing catalytic polypeptide-like (APOBEC)3 (A3) genes has garnered increasing attention in recent years, with considerable efforts focused on understanding their apparent roles in both viral editing and in HPV-driven carcinogenesis. H...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1530/JME-19-0011
更新日期:2019-05-01 00:00:00
abstract::The effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3; 10 nmol/l) on the human monomyelocytic cell line U937 were investigated. Addition of 1,25-(OH)2D3 led to a decrease in cell proliferation which fell at 72 h to 67.8 +/- 4.3% (mean +/- S.E.M.) of control values. The presence of CD14, a surface marker found on matur...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0030043
更新日期:1989-07-01 00:00:00
abstract::Glucagon-like peptide 1 (GLP1) is an intestinal incretin that regulates glucose homeostasis through stimulation of insulin secretion from pancreatic β-cells and inhibits appetite by acting on the brain. Thus, it is a promising therapeutic agent for the treatment of type 2 diabetes mellitus and obesity. Studies using s...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1530/JME-13-0137
更新日期:2014-06-01 00:00:00
abstract::The chemokine Stromal-derived factor-1alpha (SDF-1alpha) interacts with seven transmembrane (TM) G-protein-coupled receptor (GPR), CXCR4. SDF-1alpha is linked to inflammation, chemoattraction, cancer metastasis, and hematopoiesis. Tachykinin (Tac1) peptides bind seven transmembrane (TM), GPR and are involved in tumor ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-07-0111
更新日期:2008-03-01 00:00:00
abstract::Transformation of Escherichia coli cells with a recombinant plasmid containing modified mouse prolactin (mPRL) cDNA and a pKK223-3 vector resulted in efficient expression of mPRL protein. Cloned mPRL cDNA was modified by removing the 5' non-translating sequence as well as the sequence which encoded the signal peptide ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0080165
更新日期:1992-04-01 00:00:00
abstract::Thyroid hormones regulate growth, development, differentiation, and metabolic processes by interacting with and activating thyroid hormone receptors and associated pathways. We investigated the triiodothyronine (T3) modulation of gene expression, in human hepatocellular carcinoma cell lines, via a PCR-based cDNA subtr...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.01505
更新日期:2004-10-01 00:00:00
abstract::In this study we examine changes in the cellular properties of FRTL-5 cells as a function of passage number, with particular emphasis on gap junction expression, karyotype, morphology, growth rate and thyroxine (T(4)) release. Early passage FRTL-5 follicular cells transfer dye through gap junctions from injected cell(...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0270145
更新日期:2001-10-01 00:00:00
abstract::Malic enzyme 1 (ME1) is a cytosolic protein that catalyzes the conversion of malate to pyruvate while concomitantly generating NADPH from NADP. Early studies identified ME1 as a mediator of intermediary metabolism primarily through its participatory roles in lipid and cholesterol biosynthesis. ME1 was one of the first...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1530/JME-20-0176
更新日期:2020-11-01 00:00:00
abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) is synthesized from a precursor, which includes the PACAP-related peptide (PRP; formerly known as GHRH-like peptide). PRP can act as a hypophysiotropic factor in teleosts by stimulating GH secretion. However, no information points to this peptide as a regulato...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-10-0065
更新日期:2011-03-03 00:00:00
abstract::Secretion of parathyroid hormone-related protein (PTHrP) by sheep fetal parathyroid glands is reported to be an important factor in the maintenance of a placental calcium pump. The aim of the present study was to determine whether the developing rat parathyroid glands express PTHrP or parathyroid hormone (PTH), or bot...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0170149
更新日期:1996-10-01 00:00:00
abstract::Leptin (Lep) is an anorexigenic hormone and regulates appetite-related neuropeptides in mammals. A number of neuropeptides have also been linked to appetite regulation in teleost fish, but Lep signaling activation and effects on appetite-regulating neurons are poorly elucidated in early vertebrates. This study uses ce...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-15-0279
更新日期:2016-04-01 00:00:00
abstract::Two marsupial casein genes have been isolated from a tammar wallaby (Macropus eugenii) mammary gland cDNA library. Comparisons of the tammar alpha- and beta-casein genes with their eutherian homologous reveal extensive divergence at the levels of nucleotide and amino acid sequences. Regions of similarity between the t...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0080013
更新日期:1992-02-01 00:00:00
abstract::cDNAs encoding the glycoprotein hormone alpha- and gonadotropin (GTH) II beta-subunits of Japanese eel (Anguilla japonica) pituitary were cloned using the polymerase chain reaction. The nucleotide sequence of the glycoprotein hormone alpha-subunit cDNA was 364 base pairs (bp) long, encoding 117 amino acids, and that o...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0160171
更新日期:1996-04-01 00:00:00
abstract::Seven bovine follistatin (FS) cDNA clones were isolated from a bovine ovarian follicle cDNA library. The predicted amino acid sequences revealed that six of the cDNA clones represented an FS precursor of 344 amino acids which corresponded to a mature FS of 315 amino acids (FS 315), with one cDNA clone containing the e...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0130321
更新日期:1994-12-01 00:00:00
abstract::Bisphenol A (BPA) is a xenobiotic endocrine-disrupting chemical. In vitro and in vivo studies have indicated that BPA alters endocrine-metabolic pathways in adipose tissue, which increases the risk of metabolic disorders and obesity. BPA can affect adipose tissue and increase fat cell numbers or sizes by regulating th...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-14-0282
更新日期:2015-06-01 00:00:00
abstract::Reproductive function in mammals is regulated by the pituitary gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH are secreted by the gonadotrope cell and act on the gonad in a sequential and synergistic manner to initiate sexual maturation and maintain cyclic reproductive functi...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1677/jme.1.01600
更新日期:2004-12-01 00:00:00
abstract::It has been suggested that the thyroid itself may contribute to the inflammatory process observed in autoimmune thyroiditis by releasing the cytokines interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8), but studies of cytokine gene expression in thyrocytes have been limited and conflicting...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0150011
更新日期:1995-08-01 00:00:00
abstract::The melanocortin 2 receptor accessory protein (MRAP) was originally discovered to be an essential co-receptor for the ACTH receptor/melanocortin 2 receptor, and it physically interacts with this receptor and is required for receptor trafficking and ligand binding. A related molecule, MRAP2, is mainly expressed in the ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1530/JME-17-0002
更新日期:2017-04-01 00:00:00
abstract::We have generated hybridomas which secrete monoclonal antibodies to the AT1 subtype of the angiotensin II receptor (AT1 receptor). These were obtained after immunization of Balb C/c mice with synthetic peptides representing sequences from either the extracellular domain (residues 8-17) or the intracellular domain (res...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0110241
更新日期:1993-10-01 00:00:00
abstract::The mannose 6-phosphate/IGF 2 receptor (IGF2R) is comprised of 15 extra-cellular domains that bind IGF2 and mannose 6-phosphate ligands. IGF2R transports ligands from the Golgi to the pre-lysosomal compartment and thereafter to and from the cell surface. IGF2R regulates growth, placental development, tumour suppressio...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-08-0154
更新日期:2009-04-01 00:00:00
abstract::We recently reported that genetic deletion of myeloperoxidase (MPO) alleviates obesity-related insulin resistance in mice in vivo. How MPO impairs insulin sensitivity in adipocytes is poorly characterized. As hypochlorous acid (HOCl) is a principal oxidant product generated by MPO, we evaluated the effects of HOCl on ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-14-0213
更新日期:2015-02-01 00:00:00
abstract::We have cloned a full length cDNA coding for the activin type IIB receptor (GactRIIB) from the goldfish ovary. GactRIIB shares 73 and 70% amino acid identity in the extracellular domain, and 78 and 80% identity in the intracellular domain with the type IIB receptors of the mouse and Xenopus respectively. The intracell...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0190047
更新日期:1997-08-01 00:00:00
abstract::Several hormone agonists exert their physiological actions by triggering an inositol phospholipid-Ca2+ signalling cascade and cytosolic alkalinization. Although calcium ionophores have been used extensively to probe the role of Ca2+ in the regulation of steroidogenesis in granulosa cells, the precise relationship betw...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0090001
更新日期:1992-08-01 00:00:00
abstract::Decreased suppressors of cytokine signaling (SOCS) activity in human gestational tissues may play a part in the onset/progression of term labor. Since SOCS proteins negatively regulate cytokine-mediated inflammatory processes, we hypothesized that SOCS proteins are elevated in gestational tissues from spontaneous pret...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.01767
更新日期:2005-08-01 00:00:00
abstract::The p160 coactivators, steroid receptor coactivator-1 (SRC-1), transcriptional intermediary factor-2 (TIF2) and receptor-associated coactivator-3 (RAC3), as well as the coactivator/integrator CBP, mediate estrogen receptor-alpha (ERalpha)-dependent gene expression. Although these coactivators are widely expressed, ERa...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0320307
更新日期:2004-02-01 00:00:00
abstract::Activation of the hypothalamo-pituitary-adrenal (HPA) axis during stress is associated with increased expression of genes that code for regulatory hormones such as corticotrophin-releasing factor (CRF) and ACTH. The identity of the transcription factors that mediate these changes in gene expression is not known. In th...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0190291
更新日期:1997-12-01 00:00:00
abstract::A subset of over-expressed microRNAs (miRNAs) identified in parathyroid carcinomas (Ca) compared to normal glands belongs to C19MC, a cluster on chromosome 19q13.4 involved in stem cell biology and tumourigenesis. In this study, the expression of C19MC-MIR371-3 clusters and the molecular mechanisms presiding their mod...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-11-0189
更新日期:2012-07-26 00:00:00
abstract::Intracellular glucocorticoid (GC) receptor (GR) function determines tissue sensitivity to GCs and strongly affects the development of type 2 diabetes and obesity. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) mediates intracellular steroid exposure to mouse liver GR by prereceptor reactivation of GCs and is...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-08-0004
更新日期:2008-08-01 00:00:00