Effects of High Fructose/Glucose on Nlrp3/Il1ß Inflammatory Pathway

Abstract

artery disease, hypertension, metabolic syndrome, gall bladder disease, cancer, osteoarthritis and type 2 diabetes (Rodriguez-Hernandez, Simental-Mendia, Rodriguez-Ramirez, & Reyes-Romero, 2013). Among the obesity related diseases, type 2 diabetes has recently been classified an autoimmune disease involving inflammation through NLRP3 activation (Bray, 2004; Gunter & Leitzmann, 2006; Hajer, Haeften, & Visseren 2008). Studies have investigated the relationship between type 2 diabetes, insulin resistance and IL1β expression (Gao et al, 2014; Larsen et al, 2007). Larsen et al.’s experimental results (2007) showed that blockade of IL-1β expression in patients with type 2 diabetes improved β-cell function and promoted glycemic control while Goa et al.’s results (2014) showed that IL-1β presence in human adipocytes significantly reduced the gene expression of insulin signaling molecules and its absence improved insulin sensitivity. The secretion of IL-1β is regulated by the Nod-Like Receptor protein 3 (NLRP3) inflammasome. IL-1β secretion is carried out in two steps. The first signal, also known as the priming step, consists of activation of Nod-Like Receptor protein 3 (NLRP3) coupled with accumulation of proIL-1β the inactivated precursor protein for IL-1β. Upon accumulation of the precursor, a second signal is needed to recruit the NLRP3 inflammasome complex, consisting of (NLRP3), adaptor protein apoptosis speck-like Protein (ASC) and activated caspase 1, consequently responsible for cleavage of pro-IL-1β to secretion as Il-1β (Figure 1). When NLRP3/IL-1β pathway is activated, ROS production is also observed (Jo, Kim, Shin, & Sasakawa et al, 2016). An article (Tschopp & Schroder, 2010) suggested that mitochondrial ROS is not only correlated with NLRP3 activation, but is involved in assembling the NLRP3 inflammasome complex. Mitochondria are considered the main source of ROS in INTRODUCTION Western culture has adopted a diet rich in energy-loaded carbohydrates. This increased consumption of high-energy foods has been accompanied by reliance on mechanical technology to do work, reducing necessary physical activity (Popkin, 2001). The ratio of energy consumed to energy spent is imbalanced in favor of consumption, which results in storage of fat cells as adipose tissue and uncontrolled deposition of fats could lead to an individual carrying an excess amount of weight, referred to as being overweight or obese. This condition can be defined using the body mass index (BMI) of an individual (Finucane et al, 2011). Higher BMIs correspond to excess weight and obesity. Studies (Finucane et al, 2011) show that the mean BMI worldwide has increased over the years and so has the rate of obesity. In 2008, over 500 million people worldwide were considered obese and about 1.46 billion were overweight (Finucane et al, 2011). In obese individuals, enlarged fat cells secrete fatty acids and cytokine factors such as tumor necrosis factor-α (TNF-α), that are capable of causing a wide range of downstream effects such as having higher risks for a variety of diseases including coronary Effects of High Fructose/Glucose on Nlrp3/Il1ß Inflammatory Pathway