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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Adipocyte differentiation is inhibited by melatonin through the regulation of C/EBP beta transcriptional activity

Texto completo
Autor(es):
Cardoso Alonso-Vale, Maria Isabel [1] ; Peres, Sidney Barnabe [2] ; Vernochet, Cecile [2] ; Farmer, Stephen R. [2] ; Lima, Fabio Bessa [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo - Brazil
[2] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 - USA
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Journal of Pineal Research; v. 47, n. 3, p. 221-227, OCT 2009.
Citações Web of Science: 50
Resumo

Considering that melatonin has been implicated in body weight control, this work investigated whether this effect involves the regulation of adipogenesis. 3T3-L1 preadipocytes were induced to differentiate in the absence or presence of melatonin (10(-3) m). Swiss-3T3 cells ectopically and conditionally (Tet-off system) over-expressing the 34 kDa C/EBP beta isoform (Swiss-LAP cells) were employed as a tool to assess the mechanisms of action at the molecular level. Protein markers of the adipogenic phenotype were analyzed by Western blot. At 36 hr of differentiation of 3T3-L1 preadipocytes, a reduction of PPAR gamma expression was detected followed by a further reduction, at day 4, of perilipin, aP2 and adiponectin protein expression in melatonin-treated cells. Real-time PCR analysis also showed a decrease of PPAR gamma (60%), C/EBP alpha (75%), adiponectin (30%) and aP2 (40%) mRNA expression. Finally, we transfected Swiss LAP cells with a C/EBP alpha gene promoter/reporter construct in which luciferase expression is enhanced in response to C/EBP beta activity. Culture of such transfected cells in the absence of tetracycline led to a 2.5-fold activation of the C/EBP alpha promoter. However, when treated with melatonin, the level of C/EBP alpha promoter activation by C/EBP beta was reduced by 50% (P = 0.05, n = 6). In addition, this inhibitory effect of melatonin was also reflected in the phenotype of the cells, since their capacity to accumulate lipids droplets was reduced as confirmed by the poor staining with Oil Red O. In conclusion, melatonin at a concentration of 10(-3) m works as a negative regulator of adipogenesis acting in part by inhibiting the activity of a critical adipogenic transcription factor, C/EBP beta. (AU)

Processo FAPESP: 04/14696-8 - Regulação pela melatonina da expressão gênica e das funções endócrinas e metabólicas de adipócitos isolados de tecido adiposo branco em cultura primária
Beneficiário:Maria Isabel Cardoso Alonso-Vale
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 07/50404-0 - Influência da melatonina na regulação da adipogênese
Beneficiário:Maria Isabel Cardoso Alonso-Vale
Linha de fomento: Bolsas no Exterior - Pesquisa
Processo FAPESP: 04/06767-2 - O papel da melatonina no controle do metabolismo energético: interações hormonais, ações centrais e periféricas (pineal, obesidade, diabetes e envelhecimento)
Beneficiário:José Cipolla Neto
Linha de fomento: Auxílio à Pesquisa - Temático