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  • Obesity is defined as a body mass index

    2024-07-09

    Obesity is defined as a body mass index (BMI) of 30kg/m2 or higher and is known to have a very close association with the risk of developing cancers (Hsueh and Deng, 2016). Several theories exist as to how this link is defined with respect to various cancers, one of which involves the effect of obesity on the secretion of adipokines, specifically that of adiponectin (APN) (Vucenik et al., 2016). APN is known to function as a regulator of cell growth within the body via the stimulation of several other pathways and obesity is well known to cause a significant decrease in the levels of this hormone (Hsueh and Deng, 2016) (Fig. 1). Other theories focus on obesity causing a spike in ionophore resistance, inflammation, oxidative stress and lowered immune responses (Hsueh and Deng, 2016). Therefore, obesity can be controlled at the initial level by diet and physical exercise to avoid acquiring obesity-related diseases. CRC and PC affect around 940,000 and 250,000 people in the world, respectively, according to World Health Organization statistics. Extensive research suggests that obesity and APN are related to cancer development (Kelesidis et al., 2006). Among adipokines and adipocytokines in the body, APN is one of the most abundantly secreted proteins by adipose tissue (Stefan et al., 2002). Recent significant developments in areas related to APN research are described in this review. Based on the existing literature, this review is focused on APN and its effect on cancer progression, specifically with respect to CRC and PC (Otani et al., 2017, Kawashima et al., 2017, Karnati et al., 2017). In addition, the prospective therapeutic applications of this adipocyte-secreted protein hormone will also be highlighted.
    Adiponectin structure and expression APN protein has four different domains and can exist as trimers, hexamers, or multimers before it is secreted (Dalamaga et al., 2012). The protein encompasses a signal peptide, followed by a variable region, a collagen-like region, and a globular region which binds to the APN receptors (Nagaraju et al., 2016, Nagaraju et al., 2015, Simpson and Whitehead, 2010) (Fig. 2). APN trimers (LMW, Low molecular weight) associate with the collagenous domains of hexamers (MMW, medium molecular weight) and finally into high molecular weight (HMW) multimers (Wang et al., 2006). The collagen domain of MMW permits oligomerization by a disulfide bond, glycosylation and hydroxylation of four conserved lysine molecules are essential for the development of its HMW complex (Simpson and Whitehead, 2010, Wang et al., 2006). Posttranslational modifications of APN are key determinants of its function and also result in binding to APN receptors (Simpson and Whitehead, 2010). For example, post-translational changes to the four lysine molecules in the collagenous domain of APN increase the concentrations of insulin and inhibit gluconeogenesis in hepatocytes (Wang et al., 2002). The biologically active form of the hormone might be the HMW isoform as it mediates the majority of APN’s effects in endothelial cells and the liver (Wang et al., 2002). Studies on APN structure remain an evolving area of active research.
    Biology and physiology of adiponectin APN is mainly secreted by white fat tissue, but it can also be produced by brown adipose tissue to a small extent (Wang and Scherer, 2016, Chen et al., 2014). APN is also known by other names, including Acrp30, AdipoQ, apM1 and GBP28 (Chen et al., 2014). The APN gene is located on chromosome 3q27 and any changes in its structure can result in post-translational modifications to the protein’s function within the body, resulting in various clinical conditions including metabolic syndrome, cardiovascular diseases, and type 2 diabetes (Dalamaga et al., 2012, Chen et al., 2014). APN has multiple effects on various tissues and organs, which may result from different physiological functions of its isoforms on different targets (Nagaraju et al., 2016, Ziemke and Mantzoros, 2010). One of the crucial effects of APN is its regulation of glucose and lipid metabolism (Hada et al., 2007). Overall, the defensive effects of APN against inflammation and insulin resistance are due to its capacity to control lipid and simple carbohydrate profiles (Berg et al., 2001). APN is known to modulate vascular remodeling and suppress endothelial cell migration and adhesion (Ouchi et al., 2000). Additionally, APN plays a key role in bone homeostasis (Tilg and Moschen, 2006).