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  • Recently the novel fatty acid receptor GPR also called

    2021-10-16

    Recently, the novel fatty protein kinase g receptor, GPR120 (also called FFAR4), has been shown to be implicated in diverse physiological homeostasis, such as insulin sensitization, anti-inflammation and regulation of appetite (Hirasawa et al., 2005, Oh et al., 2010). Notably, it is abundantly expressed in WAT and mature adipocytes, whereas it is undetectable in preadipocytes (Gotoh et al., 2007, Ichimura et al., 2012, Miyauchi et al., 2009, Oh et al., 2010). GPR120 knockdown reduces the expression of PPARγ and fatty acid binding protein 4 (FABP4, also known as aP2) in 3T3-L1 adipocytes (Gotoh et al., 2007). Consistently, suppression of these adipogenic marker genes was detected in the mouse-embryonic fibroblast (MEF) derived adipocytes isolated from the GPR120-deficient mouse (Ichimura et al., 2012). These evidences indicate that GPR120 contributes to the process of adipogenesis. However, its precise molecular function in the regulation of adipogenic processes remains unclear. As a G protein-coupled receptor (GPCR), GPR120 is located in the cell surface and induces a wide range of cellular responses when responding to appropriate ligand binding. Several experimental observations showed that GPR120 stimulated by fatty acids or synthetic agonists increases intracellular calcium concentration ([Ca2+]i) and elevates the phosphorylation level of extracellular signal-regulated kinase1/2 (ERK1/2) cascade (Hirasawa et al., 2005, Hudson et al., 2013, Ichimura et al., 2012, Katsuma et al., 2005). ERK1/2 facilitates the early stage of adipogenic differentiation but needs to be turned off at the adipocyte maturation phase, suggesting a dual role of ERK1/2 in adipogenesis (Bost et al., 2005b, Prusty et al., 2002). On the other hand, [Ca2+]i also plays a time-dependent role in adipogenesis. Improving intracellular calcium concentration inhibits the early stage but accelerates the maturation stage of adipogenic differentiation in both murine and human adipocyte (Neal and Clipstone, 2002, Shi et al., 2000). Hence, it would be interesting to understand the roles of [Ca2+]i and ERK1/2 signaling in GPR120-induced adipogenesis. In this study, we determined the expression of GPR120 during the differentiation progress of 3T3-L1 adipocytes and found that GPR120 facilitates 3T3-L1 adipogenesis. Moreover, we for the first time showed that [Ca2+]i and ERK1/2 signaling contributes to GPR120-induced adipogenesis.
    Materials and methods
    Results
    Discussion Until now, there have been increasing evidences demonstrating that the adipose tissue has profound effects on glucose and energy homeostasis (Rosen and Spiegelman, 2014). The adipogenesis process is regulated by a large body of factors ranging from the extracellular space to the nuclear depot and involves a complex and orchestrated program of adiposity-related gene expression (Otto and Lane, 2005, Tang and Lane, 2012). Several studies have demonstrated that GPR120 may function as a novel fatty acid sensor/receptor and play a notable role in regulating obesity both in vivo and in vitro (Gotoh et al., 2007, Ichimura et al., 2012, Oh et al., 2010). Understanding the role and underlying mechanism of GPR120 in adipogenesis will undoubtedly facilitate the understanding of the relationship between selective fatty acids and obesity and obesity-related disease. The 3T3-L1 preadipocyte is a good model in vitro for characterizing preadipocyte differentiation and faithfully recapitulating the adipogenic step from preadipocytes to adipocytes (Tang and Lane, 2012). By using RNAi, Gotoh et al. reported that GPR120 knock-down in 3T3-L1 cells inhibited adipogenesis. In the present study, the adipogenic ability was significantly inhibited in shGPR120 transfected cells, indicating that GPR120 may play a role in adipogenesis. An earlier study has shown that high expression of GPR120 was detected in four kinds of mouse fat tissues and the differentiated adipocytes but not in preadipocytes (Gotoh et al., 2007, Miyauchi et al., 2009). In this study, we found that the mRNA level of GPR120 was undetectable in the initial stage of differentiation but was dramatically increased after 2-day induction of 3T3-L1 cells. Therefore, the 2 day-differentiated 3T3-L1 cells were incubated with natural ligands and a synthetic agonist (TUG-891) (Shimpukade et al., 2012) to clarify the role of GPR120 in the adipogenesis.