Obesity and Systemic Inflammation: Insights into Epigenetic Mechanisms

Abstract

The global incidence and prevalence of obesity increase with every passing year, affecting both developed and developing countries. An appalling estimate of 75% of adults are projected to be overweight or obese in the United States by 2015 (Wang and Beydoun, 2007), thus raising serious concerns regarding the social and economic repercussions of obesity. The etiology of obesity is complex, with both genetic and environmental factors influencing its susceptibility and development (Campion et al., 2009; Russo et al., 2010). The detrimental effect of obesity on metabolic, cardiovascular and central nervous system dysfunction is well documented, as is its association with type 2 diabetes and cancer (Andersson et al., 2008; Bruce-Keller et al., 2009; Gallagher and LeRoith, 2010). The continuing study of the adipose tissue over the past twenty years has transformed the perception that most investigators had of that organ. Despite being considered for decades no more than an uninteresting container for the storage of spare energy endowed with some useful mechanical and thermal insulating characteristics, the white adipose tissue (WAT) is actually an extremely dynamic endocrine organ that secretes a wide variety of hormones and cytokines, some of them in exclusivity, such as adiponectin (Zhang et al., 1994; Scherer et al., 1995; Kershaw and Flier, 2004; Trayhurn and Wood, 2004). Well over fifty adipokines have been described to date, with pleiotropic functions that highlight the involvement of the adipose tissue in the regulation of processes as varied as insulin sensitivity and glucose homeostasis, blood pressure, angiogenesis, fertility, immunity, neuroplasticity or inflammation (Trayhurn and Wood, 2004; Dietrich and Horvarth, 2009; Galic et al., 2010). Obesity is defined by excess accumulation of white adipose mass, resulting from both an increase in adipocyte cell size (hypertrophy) and the development of new mature cells from undifferentiated precursors (hyperplasia) (Heine et al., 2000; Naaz et al., 2004). Serum levels of most adipokines increase with obesity, whereas others, notably adiponectin, decrease, upsetting the energetic balance of the organism (Trayhurn and Wood, 2004; Smith et al., 2006). Most importantly, the enlarged obese adipose tissue displays enhanced macrophage infiltration and behaves as a chronically inflamed organ (Weisberg et al., 2003; Xu et al., 2003). The process of inflammation has evolved as a mechanism to repair a tissue after infection or physical damage has taken place. The acute inflammatory response is a controlled process initiated by tissue resident macrophages that after detecting infection or injury secrete a