Base de dados : MEDLINE
Pesquisa : A10.165.114.161 [Categoria DeCS]
Referências encontradas : 25 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 3 ir para página          

  1 / 25 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29339725
[Au] Autor:Velazquez-Villegas LA; Perino A; Lemos V; Zietak M; Nomura M; Pols TWH; Schoonjans K
[Ad] Endereço:Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland.
[Ti] Título:TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue.
[So] Source:Nat Commun;9(1):245, 2018 01 16.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Remodelling of energy storing white fat into energy expending beige fat could be a promising strategy to reduce adiposity. Here, we show that the bile acid-responsive membrane receptor TGR5 mediates beiging of the subcutaneous white adipose tissue (scWAT) under multiple environmental cues including cold exposure and prolonged high-fat diet feeding. Moreover, administration of TGR5-selective bile acid mimetics to thermoneutral housed mice leads to the appearance of beige adipocyte markers and increases mitochondrial content in the scWAT of Tgr5 mice but not in their Tgr5 littermates. This phenotype is recapitulated in vitro in differentiated adipocytes, in which TGR5 activation increases free fatty acid availability through lipolysis, hence fuelling ß-oxidation and thermogenic activity. TGR5 signalling also induces mitochondrial fission through the ERK/DRP1 pathway, further improving mitochondrial respiration. Taken together, these data identify TGR5 as a druggable target to promote beiging with potential applications in the management of metabolic disorders.
[Mh] Termos MeSH primário: Tecido Adiposo Bege/metabolismo
Tecido Adiposo Branco/metabolismo
Dinâmica Mitocondrial
Receptores Acoplados a Proteínas-G/metabolismo
[Mh] Termos MeSH secundário: Células 3T3-L1
Adipócitos Bege/metabolismo
Adipócitos Brancos/metabolismo
Tecido Adiposo Bege/citologia
Tecido Adiposo Branco/citologia
Animais
Diferenciação Celular/genética
Linhagem Celular
Ácidos Graxos não Esterificados/metabolismo
Seres Humanos
Camundongos
Camundongos Knockout
Receptores Acoplados a Proteínas-G/genética
Transdução de Sinais/genética
Gordura Subcutânea/citologia
Gordura Subcutânea/metabolismo
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fatty Acids, Nonesterified); 0 (Gpbar1 protein, mouse); 0 (Receptors, G-Protein-Coupled)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02068-0


  2 / 25 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28842503
[Au] Autor:McQueen AE; Kanamaluru D; Yan K; Gray NE; Wu L; Li ML; Chang A; Hasan A; Stifler D; Koliwad SK; Wang JC
[Ad] Endereço:From the Metabolic Biology Graduate Program and.
[Ti] Título:The C-terminal fibrinogen-like domain of angiopoietin-like 4 stimulates adipose tissue lipolysis and promotes energy expenditure.
[So] Source:J Biol Chem;292(39):16122-16134, 2017 Sep 29.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Angptl4 (Angiopoietin-like 4) is a circulating protein secreted by white and brown adipose tissues and the liver. Structurally, Angptl4 contains an N-terminal coiled-coil domain (CCD) connected to a C-terminal fibrinogen-like domain (FLD) via a cleavable linker, and both full-length Angptl4 and its individual domains circulate in the bloodstream. Angptl4 inhibits extracellular lipoprotein lipase (LPL) activity and stimulates the lipolysis of triacylglycerol stored by adipocytes in the white adipose tissue (WAT). The former activity is furnished by the CCD, but the Angptl4 domain responsible for stimulating adipocyte lipolysis is unknown. We show here that the purified FLD of Angptl4 is sufficient to stimulate lipolysis in mouse primary adipocytes and that increasing circulating FLD levels in mice through adenovirus-mediated overexpression (Ad-FLD) not only induces WAT lipolysis but also reduces diet-induced obesity without affecting LPL activity. Intriguingly, reduced adiposity in Ad-FLD mice was associated with increased oxygen consumption, fat utilization, and the expression of thermogenic genes ( and ) in subcutaneous WAT. Moreover, Ad-FLD mice exhibited increased glucose tolerance. Chronically enhancing WAT lipolysis could produce ectopic steatosis because of an overflow of lipids from the WAT to peripheral tissues; however, this did not occur when Ad-FLD mice were fed a high-fat diet. Rather, these mice had reductions in both circulating triacylglycerol levels and the mRNA levels of lipogenic genes in the liver and skeletal muscle. We conclude that separating the FLD from the CCD-mediated LPL-inhibitory activity of full-length Angptl4 reveals lipolytic and thermogenic properties with therapeutic relevance to obesity and diabetes.
[Mh] Termos MeSH primário: Gordura Abdominal/metabolismo
Angiopoietinas/metabolismo
Metabolismo Energético
Lipólise
Modelos Biológicos
Regulação para Cima
[Mh] Termos MeSH secundário: Gordura Abdominal/citologia
Gordura Abdominal/patologia
Tecido Adiposo Bege/citologia
Tecido Adiposo Bege/metabolismo
Tecido Adiposo Bege/patologia
Adiposidade
Proteína 4 Semelhante a Angiopoietina
Angiopoietinas/sangue
Angiopoietinas/química
Angiopoietinas/genética
Animais
Células Cultivadas
Fígado/enzimologia
Fígado/metabolismo
Masculino
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Músculo Esquelético/enzimologia
Músculo Esquelético/metabolismo
Mutação
Obesidade/sangue
Obesidade/metabolismo
Obesidade/patologia
Obesidade/prevenção & controle
Oligopeptídeos/genética
Oligopeptídeos/metabolismo
Fragmentos de Peptídeos/sangue
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Domínios e Motivos de Interação entre Proteínas
Proteínas Recombinantes de Fusão/sangue
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Triglicerídeos/sangue
Triglicerídeos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ANGPTL4 protein, human); 0 (Angiopoietin-like 4 Protein); 0 (Angiopoietins); 0 (Oligopeptides); 0 (Peptide Fragments); 0 (Recombinant Fusion Proteins); 0 (Triglycerides); 98849-88-8 (FLAG peptide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170827
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.803973


  3 / 25 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28538730
[Au] Autor:Liu P; Ji Y; Yuen T; Rendina-Ruedy E; DeMambro VE; Dhawan S; Abu-Amer W; Izadmehr S; Zhou B; Shin AC; Latif R; Thangeswaran P; Gupta A; Li J; Shnayder V; Robinson ST; Yu YE; Zhang X; Yang F; Lu P; Zhou Y; Zhu LL; Oberlin DJ; Davies TF; Reagan MR; Brown A; Kumar TR; Epstein S; Iqbal J; Avadhani NG; New MI; Molina H; van Klinken JB; Guo EX; Buettner C; Haider S; Bian Z; Sun L; Rosen CJ; Zaidi M
[Ad] Endereço:Department of Medicine, and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
[Ti] Título:Blocking FSH induces thermogenic adipose tissue and reduces body fat.
[So] Source:Nature;546(7656):107-112, 2017 06 01.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the ß-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the ß-subunit of Fsh to block its action. Our studies uncover opportunities for simultaneously treating obesity and osteoporosis.
[Mh] Termos MeSH primário: Tecido Adiposo/metabolismo
Adiposidade
Subunidade beta do Hormônio Folículoestimulante/antagonistas & inibidores
Termogênese
[Mh] Termos MeSH secundário: Adipócitos/efeitos dos fármacos
Adipócitos/metabolismo
Tecido Adiposo/efeitos dos fármacos
Tecido Adiposo Bege/efeitos dos fármacos
Tecido Adiposo Bege/metabolismo
Tecido Adiposo Branco/efeitos dos fármacos
Tecido Adiposo Branco/metabolismo
Adiposidade/efeitos dos fármacos
Animais
Anticorpos/imunologia
Anticorpos/farmacologia
Dieta Hiperlipídica/efeitos adversos
Feminino
Subunidade beta do Hormônio Folículoestimulante/imunologia
Haploinsuficiência
Masculino
Camundongos
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Obesidade/tratamento farmacológico
Obesidade/prevenção & controle
Osteoporose/tratamento farmacológico
Ovariectomia
Consumo de Oxigênio/efeitos dos fármacos
Receptores do FSH/antagonistas & inibidores
Receptores do FSH/genética
Receptores do FSH/metabolismo
Termogênese/efeitos dos fármacos
Proteína Desacopladora 1/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antibodies); 0 (Follicle Stimulating Hormone, beta Subunit); 0 (Receptors, FSH); 0 (Ucp1 protein, mouse); 0 (Uncoupling Protein 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE
[do] DOI:10.1038/nature22342


  4 / 25 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28338809
[Au] Autor:Li Q; Wang K; Ma Y; Qin C; Dong C; Jin P; Wu Y; Xiong X; Li N; Hu C; Peng J; Yang Z
[Ad] Endereço:Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
[Ti] Título:Resveratrol derivative BTM-0512 mitigates obesity by promoting beige remodeling of subcutaneous preadipocytes.
[So] Source:Acta Biochim Biophys Sin (Shanghai);49(4):318-327, 2017 Apr 01.
[Is] ISSN:1745-7270
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:Recent studies revealed that sirtuin 1 (SIRT1) is involved in the regulation of energy metabolism and its agonist resveratrol showed anti-obesity effect. This study aims to determine whether BTM-0512, a novel derivative of resveratrol, acts as an antagonist of obesity and to explore its possible mechanisms. High-fat diet (HFD)-induced obese mice were intragastrically administered with BTM-0512 (5, 10, and 20 mg/kg/day) or resveratrol (10 mg/kg/day). It was found that the body weight, Lee's index, ratio of visceral adipose tissue (VAT) to body weight, and blood glucose were significantly reduced in BTM-0512-treated mice when compared with those in mice treated with resveratrol. BTM-0512 up-regulated the expressions of SIRT1, full length PRDM16 (fPRDM16), total PRDM16 (tPRDM16, including fPPRDM16 and other PRDM16 isoforms), and uncoupling protein 1 (UCP1) in both brown and subcutaneous adipose tissues. Although BTM-0512 and resveratrol also up-regulated SIRT1 and tPRDM16 levels in VAT of HFD-induced obese mice, the expressions of fPRDM16, UCP1, and TMEM26 were down-regulated. In mouse primary subcutaneous preadipocytes cultured with or without adipogenic medium, BTM-0512 up-regulated fPRDM16, tPRDM16, and UCP1 expressions, which was reversed by SIRT1 antagonists. But in cultured brown and visceral adipocytes, the UCP1 protein level showed no significant change after treatment with 1 µM of BTM-0512. Moreover, transfection with human SIRT1 plasmid reduced lipid deposit, as well as the mRNA levels of fPRDM16, UCP1, and TMEM26, in cultured human visceral adipose-derived stem cells. In conclusion, BTM-0512 has stronger anti-obesity effect than resveratrol, which might be associated with activation of beige remodeling in subcutaneous adipose tissue.
[Mh] Termos MeSH primário: Adipócitos/efeitos dos fármacos
Tecido Adiposo Bege/efeitos dos fármacos
Obesidade/prevenção & controle
Estilbenos/farmacologia
Gordura Subcutânea/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adipócitos/metabolismo
Tecido Adiposo Bege/citologia
Tecido Adiposo Bege/metabolismo
Tecido Adiposo Marrom/citologia
Tecido Adiposo Marrom/efeitos dos fármacos
Tecido Adiposo Marrom/metabolismo
Animais
Western Blotting
Peso Corporal/efeitos dos fármacos
Células Cultivadas
Proteínas de Ligação a DNA/genética
Proteínas de Ligação a DNA/metabolismo
Dieta Hiperlipídica/efeitos adversos
Expressão Gênica/efeitos dos fármacos
Seres Humanos
Masculino
Camundongos Endogâmicos C57BL
Estrutura Molecular
Obesidade/etiologia
Obesidade/metabolismo
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Sirtuína 1/genética
Sirtuína 1/metabolismo
Estilbenos/química
Gordura Subcutânea/citologia
Gordura Subcutânea/metabolismo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Proteína Desacopladora 1/genética
Proteína Desacopladora 1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3,4',5-trimethoxystilbene); 0 (DNA-Binding Proteins); 0 (PRDM16 protein, human); 0 (Prdm16 protein, mouse); 0 (Stilbenes); 0 (Transcription Factors); 0 (Uncoupling Protein 1); EC 3.5.1.- (Sirtuin 1); Q369O8926L (resveratrol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE
[do] DOI:10.1093/abbs/gmx009


  5 / 25 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28254844
[Au] Autor:Park J; Kim M; Sun K; An YA; Gu X; Scherer PE
[Ad] Endereço:Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX.
[Ti] Título:VEGF-A-Expressing Adipose Tissue Shows Rapid Beiging and Enhanced Survival After Transplantation and Confers IL-4-Independent Metabolic Improvements.
[So] Source:Diabetes;66(6):1479-1490, 2017 Jun.
[Is] ISSN:1939-327X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Adipocyte-derived vascular endothelial growth factor-A (VEGF-A) plays a crucial role in angiogenesis and contributes to adipocyte function and systemic metabolism, such as insulin resistance, chronic inflammation, and beiging of subcutaneous adipose tissue. Using a doxycycline-inducible adipocyte-specific VEGF-A-overexpressing mouse model, we investigated the dynamics of local VEGF-A effects on tissue beiging of adipose tissue transplants. VEGF-A overexpression in adipocytes triggers angiogenesis. We also observed a rapid appearance of beige fat cells in subcutaneous white adipose tissue as early as 2 days postinduction of VEGF-A. In contrast to conventional cold-induced beiging, VEGF-A-induced beiging is independent of interleukin-4. We subjected metabolically healthy VEGF-A-overexpressing adipose tissue to autologous transplantation. Transfer of subcutaneous adipose tissues taken from VEGF-A-overexpressing mice into diet-induced obese mice resulted in systemic metabolic benefits, associated with improved survival of adipocytes and a concomitant reduced inflammatory response. These effects of VEGF-A are tissue autonomous, inducing white adipose tissue beiging and angiogenesis within the transplanted tissue. Our findings indicate that manipulation of adipocyte functions with a bona fide angiogenic factor, such as VEGF-A, significantly improves the survival and volume retention of fat grafts and can convey metabolically favorable properties on the recipient on the basis of beiging.
[Mh] Termos MeSH primário: Adipócitos Bege/metabolismo
Tecido Adiposo Bege/metabolismo
Tecido Adiposo Branco/metabolismo
Diferenciação Celular/genética
Neovascularização Fisiológica/genética
Obesidade/genética
Fator A de Crescimento do Endotélio Vascular/genética
[Mh] Termos MeSH secundário: Adipócitos Bege/citologia
Tecido Adiposo/metabolismo
Tecido Adiposo/transplante
Tecido Adiposo Bege/irrigação sanguínea
Tecido Adiposo Bege/citologia
Tecido Adiposo Branco/irrigação sanguínea
Tecido Adiposo Branco/citologia
Animais
Diferenciação Celular/imunologia
Imunofluorescência
Teste de Tolerância a Glucose
Interleucina-4/imunologia
Camundongos
Reação em Cadeia da Polimerase
Gordura Subcutânea/irrigação sanguínea
Gordura Subcutânea/citologia
Gordura Subcutânea/metabolismo
Fator A de Crescimento do Endotélio Vascular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Vascular Endothelial Growth Factor A); 0 (vascular endothelial growth factor A, mouse); 207137-56-2 (Interleukin-4)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE
[do] DOI:10.2337/db16-1081


  6 / 25 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28250021
[Au] Autor:Finlin BS; Zhu B; Confides AL; Westgate PM; Harfmann BD; Dupont-Versteegden EE; Kern PA
[Ad] Endereço:Department of Medicine, Division of Endocrinology, and the Barnstable Brown Diabetes and Obesity Center, University of Kentucky, Lexington, KY.
[Ti] Título:Mast Cells Promote Seasonal White Adipose Beiging in Humans.
[So] Source:Diabetes;66(5):1237-1246, 2017 May.
[Is] ISSN:1939-327X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human subcutaneous (SC) white adipose tissue (WAT) increases the expression of beige adipocyte genes in the winter. Studies in rodents suggest that a number of immune mediators are important in the beiging response. We studied the seasonal beiging response in SC WAT from lean humans. We measured the gene expression of various immune cell markers and performed multivariate analysis of the gene expression data to identify genes that predict UCP1. Interleukin (IL)-4 and, unexpectedly, the mast cell marker CPA3 predicted UCP1 gene expression. Therefore, we investigated the effects of mast cells on UCP1 induction by adipocytes. TIB64 mast cells responded to cold by releasing histamine and IL-4, and this medium stimulated UCP1 expression and lipolysis by 3T3-L1 adipocytes. Pharmacological block of mast cell degranulation potently inhibited histamine release by mast cells and inhibited adipocyte UCP1 mRNA induction by conditioned medium (CM). Consistently, the histamine receptor antagonist chlorpheniramine potently inhibited adipocyte UCP1 mRNA induction by mast cell CM. Together, these data show that mast cells sense colder temperatures, release factors that promote UCP1 expression, and are an important immune cell type in the beiging response of WAT.
[Mh] Termos MeSH primário: Adipócitos/metabolismo
Tecido Adiposo Bege/metabolismo
Tecido Adiposo Branco/metabolismo
Mastócitos/metabolismo
RNA Mensageiro/metabolismo
Estações do Ano
Proteína Desacopladora 1/genética
[Mh] Termos MeSH secundário: Células 3T3-L1
Adipócitos/efeitos dos fármacos
Adulto
Animais
Carboxipeptidases A/genética
Degranulação Celular
Clorfeniramina/farmacologia
Temperatura Baixa
Feminino
Regulação da Expressão Gênica
Histamina/metabolismo
Antagonistas dos Receptores Histamínicos H1/farmacologia
Seres Humanos
Interleucina-4/genética
Interleucina-4/metabolismo
Lipólise
Masculino
Proteínas de Membrana/genética
Camundongos
Análise Multivariada
Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética
RNA Mensageiro/efeitos dos fármacos
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Gordura Subcutânea/metabolismo
Coxa da Perna
Proteína Desacopladora 1/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histamine H1 Antagonists); 0 (IL4 protein, human); 0 (Membrane Proteins); 0 (PPARGC1A protein, human); 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha); 0 (RNA, Messenger); 0 (TMEM26 protein, human); 0 (UCP1 protein, human); 0 (Ucp1 protein, mouse); 0 (Uncoupling Protein 1); 207137-56-2 (Interleukin-4); 3U6IO1965U (Chlorpheniramine); 820484N8I3 (Histamine); EC 3.4.17.1 (CPA3 protein, human); EC 3.4.17.1 (Carboxypeptidases A)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170303
[St] Status:MEDLINE
[do] DOI:10.2337/db16-1057


  7 / 25 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28242620
[Au] Autor:Meng W; Liang X; Chen H; Luo H; Bai J; Li G; Zhang Q; Xiao T; He S; Zhang Y; Xu Z; Xiao B; Liu M; Hu F; Liu F
[Ad] Endereço:Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center of Central South University, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
[Ti] Título:Rheb Inhibits Beiging of White Adipose Tissue via PDE4D5-Dependent Downregulation of the cAMP-PKA Signaling Pathway.
[So] Source:Diabetes;66(5):1198-1213, 2017 May.
[Is] ISSN:1939-327X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Beiging of white adipose tissue has potential antiobesity and antidiabetes effects, yet the underlying signaling mechanisms remain to be fully elucidated. Here we show that adipose-specific knockout of Rheb, an upstream activator of mechanistic target of rapamycin complex 1 (mTORC1), protects mice from high-fat diet-induced obesity and insulin resistance. On the one hand, Rheb deficiency in adipose tissue reduced mTORC1 signaling, increased lipolysis, and promoted beiging and energy expenditure. On the other hand, overexpression of Rheb in primary adipocytes significantly inhibited CREB phosphorylation and uncoupling protein 1 (UCP1) expression. Mechanistically, fat-specific knockout of Rheb increased cAMP levels, cAMP-dependent protein kinase (PKA) activity, and UCP1 expression in subcutaneous white adipose tissue. Interestingly, treating primary adipocytes with rapamycin only partially alleviated the suppressing effect of Rheb on UCP1 expression, suggesting the presence of a novel mechanism underlying the inhibitory effect of Rheb on thermogenic gene expression. Consistent with this notion, overexpression of Rheb stabilizes the expression of cAMP-specific phosphodiesterase 4D5 (PDE4D5) in adipocytes, whereas knockout of Rheb greatly reduced cellular levels of PDE4D5 concurrently with increased cAMP levels, PKA activation, and UCP1 expression. Taken together, our findings reveal Rheb as an important negative regulator of beige fat development and thermogenesis. In addition, Rheb is able to suppress the beiging effect through an mTORC1-independent mechanism.
[Mh] Termos MeSH primário: Adipócitos/metabolismo
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo
AMP Cíclico/metabolismo
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo
Metabolismo Energético/genética
Resistência à Insulina/genética
Proteínas Monoméricas de Ligação ao GTP/genética
Neuropeptídeos/genética
Obesidade/genética
[Mh] Termos MeSH secundário: Tecido Adiposo Bege/metabolismo
Tecido Adiposo Branco/metabolismo
Animais
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
Dieta Hiperlipídica
Regulação para Baixo
Regulação da Expressão Gênica
Alvo Mecanístico do Complexo 1 de Rapamicina
Camundongos
Camundongos Knockout
Complexos Multiproteicos/metabolismo
Fosforilação
Proteína Enriquecida em Homólogo de Ras do Encéfalo
Transdução de Sinais
Serina-Treonina Quinases TOR/metabolismo
Proteína Desacopladora 1/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Creb1 protein, mouse); 0 (Cyclic AMP Response Element-Binding Protein); 0 (Multiprotein Complexes); 0 (Neuropeptides); 0 (Ras Homolog Enriched in Brain Protein); 0 (Rheb protein, mouse); 0 (Ucp1 protein, mouse); 0 (Uncoupling Protein 1); E0399OZS9N (Cyclic AMP); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1); EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases); EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4); EC 3.1.4.17 (PDE4D protein, mouse); EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170301
[St] Status:MEDLINE
[do] DOI:10.2337/db16-0886


  8 / 25 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28223294
[Au] Autor:de Jong JMA; Wouters RTF; Boulet N; Cannon B; Nedergaard J; Petrovic N
[Ad] Endereço:Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
[Ti] Título:The ß -adrenergic receptor is dispensable for browning of adipose tissues.
[So] Source:Am J Physiol Endocrinol Metab;312(6):E508-E518, 2017 Jun 01.
[Is] ISSN:1522-1555
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Brown and brite/beige adipocytes are attractive therapeutic targets to treat metabolic diseases. To maximally utilize their functional potential, further understanding is required about their identities and their functional differences. Recent studies with ß -adrenergic receptor knockout mice reported that brite/beige adipocytes, but not classical brown adipocytes, require the ß -adrenergic receptor for cold-induced transcriptional activation of thermogenic genes. We aimed to further characterize this requirement of the ß -adrenergic receptor as a functional distinction between classical brown and brite/beige adipocytes. However, when comparing wild-type and ß -adrenergic receptor knockout mice, we observed no differences in cold-induced thermogenic gene expression ( , , , and ) in brown or white (brite/beige) adipose tissues. Irrespective of the duration of the cold exposure or the sex of the mice, we observed no effect of the absence of the ß -adrenergic receptor. Experiments with the ß -adrenergic receptor agonist CL-316,243 verified the functional absence of ß -adrenergic signaling in these knockout mice. The ß -adrenergic receptor knockout model in the present study was maintained on a FVB/N background, whereas earlier reports used C57BL/6 and 129Sv mice. Thus our data imply background-dependent differences in adrenergic signaling mechanisms in response to cold exposure. Nonetheless, the present data indicate that the ß -adrenergic receptor is dispensable for cold-induced transcriptional activation in both classical brown and, as opposed to earlier studies, brite/beige cells.
[Mh] Termos MeSH primário: Adipogenia
Tecido Adiposo Bege/metabolismo
Tecido Adiposo Marrom/metabolismo
Resposta ao Choque Frio
Regulação da Expressão Gênica
Gordura Intra-Abdominal/metabolismo
Receptores Adrenérgicos beta 3/metabolismo
[Mh] Termos MeSH secundário: Adipogenia/efeitos dos fármacos
Tecido Adiposo Bege/citologia
Tecido Adiposo Bege/efeitos dos fármacos
Tecido Adiposo Marrom/citologia
Tecido Adiposo Marrom/efeitos dos fármacos
Agonistas de Receptores Adrenérgicos beta 3/farmacologia
Animais
Resposta ao Choque Frio/efeitos dos fármacos
Dioxóis/farmacologia
Feminino
Regulação da Expressão Gênica/efeitos dos fármacos
Gordura Intra-Abdominal/citologia
Gordura Intra-Abdominal/efeitos dos fármacos
Masculino
Camundongos
Camundongos Knockout
RNA Mensageiro/metabolismo
Receptores Adrenérgicos beta 1/genética
Receptores Adrenérgicos beta 1/metabolismo
Receptores Adrenérgicos beta 3/química
Receptores Adrenérgicos beta 3/genética
Reprodutibilidade dos Testes
Transdução de Sinais/efeitos dos fármacos
Especificidade da Espécie
Fatores de Tempo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrb1 protein, mouse); 0 (Adrenergic beta-3 Receptor Agonists); 0 (Dioxoles); 0 (RNA, Messenger); 0 (Receptors, Adrenergic, beta-1); 0 (Receptors, Adrenergic, beta-3); 138908-40-4 (disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170223
[St] Status:MEDLINE
[do] DOI:10.1152/ajpendo.00437.2016


  9 / 25 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28220393
[Au] Autor:Liu X; Cervantes C; Liu F
[Ad] Endereço:Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center of Central South University, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
[Ti] Título:Common and distinct regulation of human and mouse brown and beige adipose tissues: a promising therapeutic target for obesity.
[So] Source:Protein Cell;8(6):446-454, 2017 Jun.
[Is] ISSN:1674-8018
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Obesity, which underlies various metabolic and cardiovascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissipation. In this review, we summarize the evolution of human brown adipose tissue (hBAT) research and discuss new in vivo methodologies for evaluating energy expenditure in patients. We highlight the differences between human and mouse BAT by integrating and comparing their cellular morphology, function, and gene expression profiles. Although great advances in hBAT biology have been achieved in the past decade, more cellular models are needed to acquire a better understanding of adipose-specific processes and molecular mechanisms. Thus, this review also describes the development of a human brown fat cell line, which could provide promising mechanistic insights into hBAT function, signal transduction, and development. Finally, we focus on the therapeutic potential and current limitations of hBAT as an anti-glycemic, anti-lipidemic, and weight loss-inducing 'metabolic panacea'.
[Mh] Termos MeSH primário: Tecido Adiposo Bege
Tecido Adiposo Marrom
Obesidade
[Mh] Termos MeSH secundário: Tecido Adiposo Bege/metabolismo
Tecido Adiposo Bege/patologia
Tecido Adiposo Marrom/metabolismo
Tecido Adiposo Marrom/patologia
Animais
Linhagem Celular
Metabolismo Energético
Seres Humanos
Camundongos
Obesidade/metabolismo
Obesidade/patologia
Obesidade/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170222
[St] Status:MEDLINE
[do] DOI:10.1007/s13238-017-0378-6


  10 / 25 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28109720
[Au] Autor:Kalinovich AV; de Jong JM; Cannon B; Nedergaard J
[Ad] Endereço:Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
[Ti] Título:UCP1 in adipose tissues: two steps to full browning.
[So] Source:Biochimie;134:127-137, 2017 Mar.
[Is] ISSN:1638-6183
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The possibility that brown adipose tissue thermogenesis can be recruited in order to combat the development of obesity has led to a high interest in the identification of "browning agents", i.e. agents that increase the amount and activity of UCP1 in brown and brite/beige adipose tissues. However, functional analysis of the browning process yields confusingly different results when the analysis is performed in one of two alternative steps. Thus, in one of the steps, using cold acclimation as a potent model browning agent, we find that if the browning process is followed in mice initially housed at 21 °C (the most common procedure), there is only weak molecular evidence for increases in UCP1 gene expression or UCP1 protein abundance in classical brown adipose tissue; however, in brite/beige adipose depots, there are large increases, apparently associating functional browning with events only in the brite/beige tissues. Contrastingly, in another step, if the process is followed starting with mice initially housed at 30 °C (thermoneutrality for mice, thus similar to normal human conditions), large increases in UCP1 gene expression and UCP1 protein abundance are observed in the classical brown adipose tissue depots; there is then practically no observable UCP1 gene expression in brite/beige tissues. This apparent conundrum can be resolved when it is realized that the classical brown adipose tissue at 21 °C is already essentially fully differentiated and thus expands extensively through proliferation upon further browning induction, rather than by further enhancing cellular differentiation. When the limiting factor for thermogenesis, i.e. the total amount of UCP1 protein per depot, is analyzed, classical brown adipose tissue is by far the predominant site for the browning process, irrespective of which of the two steps is analyzed. There are to date no published data demonstrating that alternative browning agents would selectively promote brite/beige tissues versus classical brown tissue to a higher degree than does cold acclimation. Thus, to restrict investigations to examine adipose tissue depots where only a limited part of the adaptation process occurs (i.e. the brite/beige tissues) and to use initial conditions different from the thermoneutrality normally experienced by adult humans may seriously hamper the identification of therapeutically valid browning agents. The data presented here have therefore important implications for the analysis of the potential of browning agents and the nature of human brown adipose tissue.
[Mh] Termos MeSH primário: Temperatura Baixa
Termogênese/genética
Proteína Desacopladora 1/genética
[Mh] Termos MeSH secundário: Aclimatação/genética
Adipócitos/citologia
Adipócitos/metabolismo
Tecido Adiposo Bege/citologia
Tecido Adiposo Bege/metabolismo
Tecido Adiposo Marrom/citologia
Tecido Adiposo Marrom/metabolismo
Animais
Diferenciação Celular
Proliferação Celular
Regulação da Expressão Gênica
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Especificidade de Órgãos
Transdução de Sinais
Proteína Desacopladora 1/agonistas
Proteína Desacopladora 1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ucp1 protein, mouse); 0 (Uncoupling Protein 1)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170216
[Lr] Data última revisão:
170216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170123
[St] Status:MEDLINE



página 1 de 3 ir para página          
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde