Human adipose tissue is involved in fat storage and also plays a role in the immune response. Adipose tissue includes various cell types as preadipocyte cells, adipocyte cells, endothelial cells, mast cells, fibroblasts, diverse immune cells, stem cells. (Recinella et al., 2020; Weschenfelder et al., 2020) It may also inhibit weight earning and metabolic diseases through the activation of specialized heat-productive adipocytes (Choe et al., 2016; Leiherer et al., 2013). Expression of transcriptional regulators such as peroxisome proliferator-activated receptor gamma (PPAR-γ) and CCAAT/enhancer binding protein α (C/EBPα), sirtuin (SIRT), transient receptor potential vanilloid receptor 1 and 2 (TRPV1, TRPV2) receptors induce the differentiation of adipocytes and adipogenesis. Previous studies revealed that TRPV1 channels take part in weight loss by enhancing intracellular Ca2+ levels (Azhar et al., 2016; Rosen et al.; 2002; Aggarwal 2010; Ohara et al., 2009; Villarroya et al., 2007; Kang et al., 2011; Chan 1995; Milne et al., 2007).
Brown adipose tissue (BAT) consists of preadipocytes that express a high level of thermogenic genes. These preadipocytes are located in special stores and play a role in providing the energy equality in the all body part by taking part in thermogenesis, converting excess amounts of chemical/nutritional energy into heat energy. In contrast, brown-like adipocyte cells, also named as beige cells, grow in white adipocyte cells in response to various activators (Azhar et al., 2016). The activity of beige and brown fat cells is important in reducing metabolic diseases, including obesity, in humans and mice (Harms and Seale, 2013). White adipose tissue (WAT) consists of adipocytes that stored energy as triglycerides. However BAT is functionally and physically different from WAT, and BMI (body mass index) adversely proportional with the amount of BAT suppression of adipocyte differentiation (from brown cells to white cells) would be an effective strategy to prevent and treat obesity (Cypess and Kahn, 2010; Boss and Farmer, 2012; Poher et al., 2015)
Activation and excessive-expression of sirtuin family (SIRTs) are contained in the trans-differentiation or “browning” course of WAT to BAT (Wang et al., 2015). Beige adipocytes are specialized in dissipating heat as energy. It does this by increasing their high mitochondrial content, and the expression of mitochondria-related genes such as uncoupling proteins (UCPs). UCPs are family of the mitochondrial anion carrier protein family targeted as weight loss therapy, with a role in controlling body temperature and energy balance (Harms and Seale, 2013).
White adipocytes produce and secrete a big number of adipokines such as growth factors, cytokines, vasodilators, hormones and others including signal molecules (Recinella et al., 2020; Weschenfelder et al., 2020). Adipokines have several functions. Regulation of appetite and energy, glucose and fat and metabolism, endothelial cell function, insulin function, inflammation, blood pressure, atherosclerosis, hemostasis, metabolic syndrome and so on are some of these functions (Moncuso, 2016; Zorena et al., 2020). Leptin, adiponectin (visfatin), inflammatory cytokines as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF- α), cyclooxygenase-2 (COX-2), iterleukin-6 (IL-6), interleukin-1 (IL-1), platelet activator inhibitor 1 (PAI-1), angiogenic proteins such as vascular endothelial growth factor (VEGF) and its receptor as vascular endothelial growth factor receptor (VEGF-R) are produced and secreted from white adipocytes. The molecular mechanisms of these adipokines’ effects haven’t fully been understood yet and the research on this is still being carried out (Chan, 1995; Fain, 2006; Pendurthi and Rao, 2000; Aggarwal et al., 2006; Woo et al., 2007; Wang et al., 2009; Lehr et al., 2012; Fasshauer and Blüher, 2015).
Various thermogenic dietary factors have been shown to prevent obesity and metabolic syndrome through antioxidant anon this d antiinflammatory mechanisms. Curcumin is a polyphenolic compound derived from the turmeric (Curcuma Longa) plant belonging to the gingerbill (Zingiberaceae) family and has a wide variety of biological and pharmacological effects (Sharma et al., 2005) In humans, there were no adverse effects when curcumin was ingested at 8 g/day for 3 months (Gupta, 2013).
The thermogenic functions of curcumin (CUR) was described to inhibit the differentiation of adipocytes from preadipocytes (Manjunatha and Srinivasan,2009) It has been reported that curcumin supresses adipocyte differentiation by affecting various regulators. Curcumin can lower the expression of PPARγ and C/EBPα leading to decrease in lipid accumulation in adipocytes and ameliorate obesity and hyperlipidemia in diseased with metabolic syndrome (Mohammadi et al., 2013; Ganjali et al., 2014). Curcumin has a potential role in reducing triglycerides. It does this by interacting with various targets, including like cholesteryl ester transfer protein (CETP), peroxisome proliferator-activated receptor alpha (PPAR-α), PPAR-γ and lipoprotein lipase (Sahebkar, 2014). Curcumin, a natural polyphenol is suggested to supress adipocyte differentiation in the early stage by inhibiting secretion of some regulators and the inflammatory cytokines and by activating the secretion of antiinflammatory cytokines. (Aggarwal, 2010; (Duvoix et al., 2005; Wongcharoen and Phrommintikul, 2009; Pivari et al., 2019; Kumar and Sharma, 2015; Gupta et al., 2017; Tanrıkulu-Küçük et al., 2019; Surh, 2002; Sahebkar et al., 2014). Curcumin is also reported to impress both the production and breakdown of triglyceride-rich lipoproteins to reduce plasma cholesterol and triglyceride concentrations by attenuating the expression of lipogenic genes (Sahebkar, 2014). It can affect through transient receptor potential vanilloid (TRPV1) receptor 1 and transient receptor potential vanilloid (TRPV2) receptor 2 located in the intestinal jejunum and thus may have effects on both WAT and BAT (Xu et al., 2003; Nalli et al., 2017; Priyanka et al., 2017).
In current study, we aimed to explore the molecular mechanisms of the inhibitory effects of different doses of curcumin on the human preadipocyte-adipocyte cell differentiation. We also examined the adequate dose of curcumin supplement to prevent adipocyte related oxidative and inflammatory status. This study was the first to examine the effect of curcumin on the human preadipocyte-adipocyte cell differentiation.
In our study, we studied the following methods with all curcumin doses we prepared and curcumin doses were studied in triplicate in all methods.