Abstract
Tyrosine phosphatase protein Shp2 is a potential therapeutic target for obesity. However, the mechanism of Shp2 during adipogenesis is not fully understood. The present study investigated the role of Shp2 in the terminal differentiation of preadipocytes. The results showed that Shp2 suppressed adipocyte differentiation in 3T3-L1 cells; overexpression of Shp2 reduced lipid droplet production in 3T3-L1 cells, whereas Shp2 knockdown increased lipid droplet production in 3T3-L1 cells. Furthermore, inhibition of Shp2 activity also enhanced adipocyte differentiation. Interestingly, Shp2 expression was specifically decreased early during differentiation in response to stimulation with the dexamethasone–methylisobutylxanthine–insulin (DMI) hormone cocktail. During the first 2 days of differentiation, Shp2 overexpression impaired the DMI-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) in 3T3-L1 cells and blocked the peak expression of CCAAT/enhancer-binding proteins β and δ during preadipocyte differentiation. In conclusion, Shp2 downregulated the early stages of hormone-induced differentiation of 3T3-L1 cells and inhibited the expression of the first wave of transcription factors by suppressing the DMI-induced STAT3 signaling pathway. These discoveries point to a novel role of Shp2 during adipogenesis and support the hypothesis that Shp2 could be a therapeutic target for the control of obesity.
Highlights
Obesity is a very serious disease that affects a large proportion of the global population.[1]
Adipogenesis occurs in two main stages: an initial commitment step, in which cells are restricted to the adipocyte lineage, and the subsequent differentiation of these preadipocytes, governed by a network of transcription factors (TFs), into the adipocyte phenotype.[5,7]
These results indicate that Shp[2] regulates the phosphorylation of extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3), but does not affect the activation of Akt induced by dexamethasone–methylisobutylxanthine– insulin (DMI) during the first 2 days of adipogenic differentiation
Summary
Obesity is a very serious disease that affects a large proportion of the global population.[1]. On day signaling protein that usually has dual regulatory effects from 8 of treatment, adipocyte differentiation was assessed by staining single signals (such as INS, growth hormone (GH), transforming growth factor α and leptin).[21,28] As a result, Shp[2] may show diverse effects on obesity depending on the context.[21,28]. These conflicting results have limited the study of Shp[2] as an the lipid droplets with Oil Red O. These results suggest that Shp[2] negatively regulates adipogenic differentiation
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