Search Results
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Noelia Martínez-Sánchez in
Google Scholar
PubMed
Department of Diabetes, Endocrinology and Nutrition, Hospital de Girona ‘Dr Josep Trueta’, Institut D’investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain
Search for other papers by José M Moreno-Navarrete in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Cristina Contreras in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Eva Rial-Pensado in
Google Scholar
PubMed
Department of Clinical Science, KG Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway
Search for other papers by Johan Fernø in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Rubén Nogueiras in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Carlos Diéguez in
Google Scholar
PubMed
Department of Diabetes, Endocrinology and Nutrition, Hospital de Girona ‘Dr Josep Trueta’, Institut D’investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain
Search for other papers by José-Manuel Fernández-Real in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Miguel López in
Google Scholar
PubMed
agonism might be a suitable strategy for the treatment of obesity. In this regard, recent data have shown that treatment with the TR agonist GC-1 promotes browning of WAT and ameliorates obesity and diabetes in mice ( Lin et al . 2015 ). In summary, our
Search for other papers by Lei Zhang in
Google Scholar
PubMed
Search for other papers by Carol Paddon in
Google Scholar
PubMed
Search for other papers by Mark D Lewis in
Google Scholar
PubMed
Search for other papers by Fiona Grennan-Jones in
Google Scholar
PubMed
Search for other papers by Marian Ludgate in
Google Scholar
PubMed
Since TSH receptor (TSHR) expression increases during adipogenesis and signals via cAMP/phospho-cAMP-response element binding protein (CREB), reported to be necessary and sufficient for adipogenesis, we hypothesised that TSHR activation would induce preadipocyte differentiation. Retroviral vectors introduced constitutively active TSHR (TSHR*) into 3T3L1 preadipocytes; despite increased cAMP (RIA) and phospho-CREB (western blot) there was no spontaneous adipogenesis (assessed morphologically, using oil red O and QPCR measurement of adipogenesis markers). We speculated that Gβγ signalling may be inhibitory but failed to induce adipogenesis using activated Gsα (gsp*). Inhibition of phosphodiesterases did not promote adipogenesis in TSHR* or gsp* populations. Furthermore, differentiation induced by adipogenic medium with pioglitazone was reduced in TSHR* and abolished in gsp* expressing 3T3L1 cells. TSHR* and gsp* did not inactivate PPARγ (PPARG as listed in the HUGO database) by phosphorylation but expression of PPARγ1 was reduced and PPARγ2 undetectable in gsp*. FOXO1 phosphorylation (required to inactivate this repressor of adipogenesis) was lowest in gsp* despite the activation of AKT by phosphorylation. PROF is a mediator that facilitates FOXO1 phosphorylation by phospho-Akt. Its transcript levels remained constantly low in the gsp* population. In most measurements, the TSHR* cells were between the gsp* and control 3T3L1 preadipocytes. The enhanced down-regulation of PREF1 (adipogenesis inhibitor) permits retention of some adipogenic potential in the TSHR* population. We conclude that Gsα signalling impedes FOXO1 phosphorylation and thus inhibits PPARγ transcription and the alternative promoter usage required to generate PPARγ2, the fat-specific transcription factor necessary for adipogenesis.
Search for other papers by Bin Li in
Google Scholar
PubMed
Beijing Institute of Hepatology, Beijing, China
Search for other papers by Jiming Yin in
Google Scholar
PubMed
Search for other papers by Jing Chang in
Google Scholar
PubMed
Search for other papers by Jia Zhang in
Google Scholar
PubMed
Search for other papers by Yangjia Wang in
Google Scholar
PubMed
Search for other papers by Haixia Huang in
Google Scholar
PubMed
Beijing Lab for Cardiovascular Precision Medicine, Beijing, China
Search for other papers by Wei Wang in
Google Scholar
PubMed
Search for other papers by Xiangjun Zeng in
Google Scholar
PubMed
cardiomyopathy ( Wang et al. 2016 ). Studies have revealed that diabetes impairs the function and structure of myocardial microvascular vessels both in diabetic patients and diabetic animal models ( Aneja et al. 2008 , Campbell et al. 2011 ), of which
Search for other papers by Antonia Hufnagel in
Google Scholar
PubMed
Search for other papers by Laura Dearden in
Google Scholar
PubMed
Search for other papers by Denise S Fernandez-Twinn in
Google Scholar
PubMed
Search for other papers by Susan E Ozanne in
Google Scholar
PubMed
Introduction Around 50% of women worldwide enter pregnancy overweight or obese ( Hill et al. 2019 ). Maternal obesity is the main risk factor for the development of gestational diabetes mellitus (GDM) in pregnancy, which affects
Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK
Search for other papers by Laura L Gathercole in
Google Scholar
PubMed
Search for other papers by Nikolaos Nikolaou in
Google Scholar
PubMed
Search for other papers by Shelley E Harris in
Google Scholar
PubMed
Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK
Search for other papers by Anastasia Arvaniti in
Google Scholar
PubMed
Search for other papers by Toryn M Poolman in
Google Scholar
PubMed
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Search for other papers by Jonathan M Hazlehurst in
Google Scholar
PubMed
Search for other papers by Denise V Kratschmar in
Google Scholar
PubMed
Search for other papers by Marijana Todorčević in
Google Scholar
PubMed
Search for other papers by Ahmad Moolla in
Google Scholar
PubMed
Search for other papers by Niall Dempster in
Google Scholar
PubMed
Search for other papers by Ryan C Pink in
Google Scholar
PubMed
Search for other papers by Michael F Saikali in
Google Scholar
PubMed
Search for other papers by Liz Bentley in
Google Scholar
PubMed
Search for other papers by Trevor M Penning in
Google Scholar
PubMed
Search for other papers by Claes Ohlsson in
Google Scholar
PubMed
Search for other papers by Carolyn L Cummins in
Google Scholar
PubMed
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland
Search for other papers by Matti Poutanen in
Google Scholar
PubMed
Search for other papers by Alex Odermatt in
Google Scholar
PubMed
Search for other papers by Roger D Cox in
Google Scholar
PubMed
Search for other papers by Jeremy W Tomlinson in
Google Scholar
PubMed
risk of type 2 diabetes ( Wei et al. 2019 ). The enzyme ∆4-3-oxosteroid 5β-reductase is encoded by the gene AKR1D1 (named Akr1d1 or Akr1d4 in mice) and catalyses an essential step in bile acid synthesis, with 5β-reduction being required for
Search for other papers by K E Lines in
Google Scholar
PubMed
Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK
Search for other papers by P J Newey in
Google Scholar
PubMed
Search for other papers by C J Yates in
Google Scholar
PubMed
Search for other papers by M Stevenson in
Google Scholar
PubMed
Search for other papers by R Dyar in
Google Scholar
PubMed
Search for other papers by G V Walls in
Google Scholar
PubMed
Search for other papers by M R Bowl in
Google Scholar
PubMed
Search for other papers by R V Thakker in
Google Scholar
PubMed
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of parathyroid, pituitary and pancreatic islet tumours, and is due to mutations of the MEN1 gene, which encodes the tumour suppressor protein menin. Menin has multiple roles in genome stability, transcription, cell division and proliferation, but its mechanistic roles in tumourigenesis remain to be fully elucidated. miRNAs are non-coding single-stranded RNAs that post-transcriptionally regulate gene expression and have been associated with tumour development, although the contribution of miRNAs to MEN1-associated tumourigenesis and their relationship with menin expression are not fully understood. Alterations in miRNA expression, including downregulation of three putative ‘tumour suppressor’ miRNAs, miR-15a, miR-16-1 and let-7a, have been reported in several tumour types including non-MEN1 pituitary adenomas. We have therefore investigated the expression of miR-15a, miR-16-1 and let-7a in pituitary tumours that developed after 12 months of age in female mice with heterozygous knockout of the Men1 gene (Men1 +/ − mice). The miRNAs miR-15a, miR-16-1 and let-7a were significantly downregulated in pituitary tumours (by 2.3-fold, P < 0.05; 2.1-fold P < 0.01 and 1.6-fold P < 0.05, respectively) of Men1 +/ − mice, compared to normal WT pituitaries. miR-15a and miR-16-1 expression inversely correlated with expression of cyclin D1, a known pro-tumourigenic target of these miRNAs, and knockdown of menin in a human cancer cell line (HeLa), and AtT20 mouse pituitary cell line resulted in significantly decreased expression of miR-15a (P < 0.05), indicating that the decrease in miR-15a may be a direct result of lost menin expression.
Search for other papers by Katie J Mylonas in
Google Scholar
PubMed
Search for other papers by Neil A Turner in
Google Scholar
PubMed
Search for other papers by Sumia A Bageghni in
Google Scholar
PubMed
Search for other papers by Christopher J Kenyon in
Google Scholar
PubMed
Search for other papers by Christopher I White in
Google Scholar
PubMed
Search for other papers by Kieran McGregor in
Google Scholar
PubMed
Search for other papers by Robert A Kimmitt in
Google Scholar
PubMed
Search for other papers by Richard Sulston in
Google Scholar
PubMed
Search for other papers by Valerie Kelly in
Google Scholar
PubMed
Search for other papers by Brian R Walker in
Google Scholar
PubMed
Search for other papers by Karen E Porter in
Google Scholar
PubMed
Search for other papers by Karen E Chapman in
Google Scholar
PubMed
Search for other papers by Gillian A Gray in
Google Scholar
PubMed
We have previously demonstrated that neutrophil recruitment to the heart following myocardial infarction (MI) is enhanced in mice lacking 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that regenerates active glucocorticoid within cells from intrinsically inert metabolites. The present study aimed to identify the mechanism of regulation. In a mouse model of MI, neutrophil mobilization to blood and recruitment to the heart were higher in 11β-HSD1-deficient (Hsd11b1 − / − ) relative to wild-type (WT) mice, despite similar initial injury and circulating glucocorticoid. In bone marrow chimeric mice, neutrophil mobilization was increased when 11β-HSD1 was absent from host cells, but not when absent from donor bone marrow-derived cells. Consistent with a role for 11β-HSD1 in ‘host’ myocardium, gene expression of a subset of neutrophil chemoattractants, including the chemokines Cxcl2 and Cxcl5, was selectively increased in the myocardium of Hsd11b1 − / − mice relative to WT. SM22α-Cre directed disruption of Hsd11b1 in smooth muscle and cardiomyocytes had no effect on neutrophil recruitment. Expression of Cxcl2 and Cxcl5 was elevated in fibroblast fractions isolated from hearts of Hsd11b1 − / − mice post MI and provision of either corticosterone or of the 11β-HSD1 substrate, 11-dehydrocorticosterone, to cultured murine cardiac fibroblasts suppressed IL-1α-induced expression of Cxcl2 and Cxcl5. These data identify suppression of CXCL2 and CXCL5 chemoattractant expression by 11β-HSD1 as a novel mechanism with potential for regulation of neutrophil recruitment to the injured myocardium, and cardiac fibroblasts as a key site for intracellular glucocorticoid regeneration during acute inflammation following myocardial injury.
Search for other papers by Gulizar Issa Ameen in
Google Scholar
PubMed
Search for other papers by Silvia Mora in
Google Scholar
PubMed
/adiponectin polymorphisms are associated with severe childhood and adult obesity . Diabetes 55 545 – 550 . ( https://doi.org/10.2337/diabetes.55.02.06.db05-0971 ) 10.2337/diabetes.55.02.06.db05-0971 16443793 Boyraz M Cekmez F Karaoglu A Cinaz P Durak
Search for other papers by Neerav Mullur in
Google Scholar
PubMed
Search for other papers by Arianne Morissette in
Google Scholar
PubMed
Department of Biochemistry, Microbiology and Immunology, The University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada
Search for other papers by Nadya M Morrow in
Google Scholar
PubMed
Department of Biochemistry, Microbiology and Immunology, The University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada
Search for other papers by Erin E Mulvihill in
Google Scholar
PubMed
GLP-1 to reduce glycemia through glucose-dependent potentiation of insulin secretion provided the initial rationale for exploring the feasibility of GLP-1R agonist (GLP-1RA)-based peptide therapies for the management of type 2 diabetes mellitus (T2DM
Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
Search for other papers by Erica Yeo in
Google Scholar
PubMed
Department of Medicine, University of Toronto, Toronto, ON, Canada
Search for other papers by Patricia L Brubaker in
Google Scholar
PubMed
Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
Department of Obstetrics, Gynecology and Pediatrics, McMaster University, Hamilton, ON, Canada
Search for other papers by Deborah M Sloboda in
Google Scholar
PubMed
. 1 ). These adaptations, however, must be finely tuned, as excessive insulin resistance and/or failure to increase β-cell mass can result in pregnancy complications including gestational diabetes mellitus (GDM, diabetes first diagnosed in pregnancy
