Human Visceral and Subcutaneous Adipocytes Differentiated In Vitro from Precursor Stromal Cells Show Differences in Insulin Action and Metabolic Responses.

Autor: Perrini, Sebastio, Laviola, Luigi, Cignarelli, Angelo, De Stefano, Francesca, Caccioppoli, Cristina, Natalicchio, Annalisa, Melchiorre, Mariangela, Orlando, Maura R., Cignarelli, Mauro, Giorgino, Riccardo, Giorgino, Francesco
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Zdroj: Diabetes; Jun2007 Supplement 1, Vol. 56, pA362-A362, 1/4p
Abstrakt: Visceral (V) and subcutaneous (SC) fat depots possess different metabolic properties that can be demonstrated both in whole-tissue specimens and isolated adipocytes. In this study, we investigated whether human adipocytes obtained from V or SC fat depots retain distinct properties also when they are differentiated in vitro from precursor stromal cells. Paired V and SC fat precursor cells from 10 non-diabetic subjects (4F/6M, age 45 ± 1 yrs, BMI 23.1 ± 1.4) were differentiated in vitro with dexamethasone, IBMX, insulin and rosiglitazone. Upon differentiation, mRNA levels of GLUT4, PPARgamma, C/EBPalpha, aP2, and adiponectin, measured by real-time RT-PCR, were markedly up-regulated (p<0.05), whereas GLUT1 expression did not change. However, mRNA expression levels of C/EBPalpha, adiponectin and aP2 were higher in V than in SC adipocytes (p<0.05). Adiponectin Secretion in the culture medium was also ∼ 3-fold higher in V than in SC adipocytes (p<0.05). Intracellular insulin signaling was next evaluated by analyzing the phosphorylation levels of various proteins after stimulation with 10 nM insulin for 5 to 120 min. Insulin-induced phosphorylation of the insulin receptor, IRS-1/2, Akt and Erk-1/2 appeared to be more rapid and tended to decrease at earlier time points in V as compared to SC adipocytes, in which more persistent protein phosphorylation in response to insulin was observed. When compared to SC adipocytes, V adipocytes also showed approx. 80% higher rates of insulin-induced 2-deoxy-D-glucose uptake. In conclusion, SC and V adipocytes, even when differentiated in vitro from precursor stromal cells, retain differences in gene expression, adiponectin secretion, and insulin action and signaling. This suggests that the precursor cells resident in V and SC fat depots possess inherent and specific metabolic characteristics that are expressed upon completion of the differentiation programme. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index