Use of vgii3 activity modulator for the modulation of adipogenesis
a technology of adipogenesis and activity modulator, which is applied in the field of vgll, can solve the problems of limited fat storage capacity in adipose tissue, excess of this capacity, and accumulation of lipids in other tissues, and achieve the effect of reducing visceral and/or subcutaneous fat accumulation
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example 1
Microarray Results
[0080]Bioinformatic analysis of the microarray data was performed to identify genes that fulfilled the three following criteria: (i) regulated by high fat feeding, (ii) similar regulated expression by high fat feeding in both visceral and subcutaneous fat and (iii) similar normalization of their expression by Rimonabant treatment (FIGS. 1A-B). Out of the ˜17′000 gene targets present on the cDNA microarray used, 34 genes fulfilled these criteria, which are listed in Table 1. Remarkably, 10 of these genes—Cav1, Fgf1, Fndc3b, Kif5b, Mest, Npr3, Pik3ca, Sparc, Vldlr, and Wwtr1—were previously known to be important regulators of adipose tissue development and function. Some of these genes had expression levels correlated with body weight gain (shown in grey in Table 1), suggesting a potential role in hyperplasia and / or hypertrophy of adipose tissues during obesity. These results validate the approach used to identify possible novel targets for therapeutic treatment of o...
example 2
Tissue and Cellular Expression of the Selected Genes
[0083]To better understand the role of Vgll3 in adipocytes development, its pattern of expression was first characterized. mRNA levels were measured by RT-PCR in various mouse tissues, in isolated preadipocytes and adipocytes, in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT) of mouse obesity model (Ob / Ob mice) and in human adipose tissues.
[0084]Vgll3 is highly expressed in kidney compared to other organs. It has a similar expression in VAT, SCAT, muscle and heart. The lowest expression is observed in liver, BAT and spleen. Vgll3 levels are normalized with cyclophilin A levels for each tissue and are expressed as relative fold increase compared to the liver level set arbitrarily at 1 (FIG. 2A).
[0085]Adipose tissue is a complex tissue that includes not only mature adipocytes, but also precursor cells such as preadipocytes as well as blood vessels, macrophages and fibroblastic cells. Based on a collagenase I dig...
example 3
Expression of Selected Genes During 3T3-L1 Differentiation
[0090]Next, the expression of Vgll3 gene was assessed during adipogenesis. For that purpose, mRNA levels were measured by RT-PCR during a detailed differentiation time-course of 3T3-L1 (an adipogenic cell line) (FIG. 2E). Interestingly, Vgll3 expression is decreased as soon as the DMI is added to the cells, and remains at very low levels during all 7 days, further suggesting that this gene is specifically down regulated to allow adipogenesis.
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