Regulation of Alstrom syndrome gene expression during adipogenesis and its relationship with fat cell insulin sensitivity.
Adipogenesis, Animals, Cell-Differentiation, Gene-Expression-Regulation, Glucose, Insulin, Mice, Proteins, RNA-Messenger, Reverse-Transcriptase-Polymerase-Chain-Reaction, Thiazolidinediones, Transcription-Genetic
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Int J Mol Med 2008 Jun; 21(6):731-6.
Alstrom syndrome (ALMS) is an autosomal recessive genetic disease with characteristic phenotypical features including multi-organ fibrosis, insulin resistance, obesity and type 2 diabetes. ALMS1, a ubiquitously expressed gene mutated in ALMS patients, gives rise to a protein of unknown function localized to basal bodies of ciliated cells and centrosomes. Together with Bardet-Biedl syndrome, ALMS is a member of genetic ciliopathies, but the link between cilia/centrosome deficits and metabolic abnormalities remains to be determined. In this study for the first time we quantified Alms1 expression in a cellular model of adipogenesis during the differentiation of 3T3-L1 cells. An early decrease in Alms1 mRNA was observed during preadipocyte to adipocyte conversion. However, acute treatment of preadipocytes with the adipogenic factors did not result in significant change of Alms1 expression. In addition, to study the possible relationship between Alms1 and the degree of fat cell insulin sensitivity, as assessed with an insulin-dependent 2-[1-3H]-deoxyglucose uptake assay, we induced either a reduction or an increase in 3T3-L1 adipocytes insulin sensitivity by a chronic treatment with insulin or rosiglitazone respectively. In all these conditions Alms1 expression remained unchanged. In conclusion, our results show that Alms1 is expressed at higher level in preadipocytes suggesting a role of the gene in the early phase of adipogenesis. Moreover, changes in fat cell insulin sensitivity do not imply any effect on Alms1 expression.
Romano, S; Milan, G; Veronese, C; Collin, G B.; Marshall, J D.; Centobene, C; Favaretto, F; Dal, Pra C.; Scarda, A; Leandri, S; Naggert, J K.; Maffei, P; and Vettor, R, "Regulation of Alstrom syndrome gene expression during adipogenesis and its relationship with fat cell insulin sensitivity." (2008). Faculty Research 2000 - 2009. 1787.