Review ArticleOmentin: A Novel Link Between Inflammation, Diabesity, and Cardiovascular Disease
Introduction
The metabolic syndrome is associated with excessive accumulation of central body fat, that is, visceral obesity. As well as adipocytes, adipose tissue (AT) contains stromal vascular cells, immune cells, and nervous tissue; these components function in concert making AT an endocrine organ (Kershaw and Flier 2004). AT produces cytokines termed adipokines that have widespread effects on carbohydrate and lipid metabolism and are implicated in the pathogenesis of insulin resistance, diabetes, and atherosclerosis (Kershaw and Flier 2004). Adipokines that are produced and secreted from adipocytes such as leptin and adiponectin are considered true adipokines in contrast to those derived from the nonadipocyte fraction of AT, for example, tumor necrosis factor–α (TNF-α). Furthermore, the accumulation of visceral AT poses a greater cardiometabolic risk than subcutaneous AT because there is higher lipolytic activity in visceral AT compared with other AT depots (Wajchenberg. 2000). The increased release of free fatty acid (FFA) and glycerol from visceral AT is dependent on the sympathetic nervous system; there is an increase of β-adrenoreceptors (lipolysis) and a decrease in α2-adrenoreceptors (antilipolysis) (Wajchenberg. 2000). Consequently, the increased FFA transport to the liver decreases hepatic insulin removal; this results in systemic hyperinsulinemia as well as inhibiting the suppression of hepatic glucose production by insulin. Chronic exposure to high levels of FFA leads to β-cell complications, which predisposes to type 2 diabetes mellitus (T2DM) and its attending cardiometabolic risks (Wajchenberg. 2000). In addition, removal of visceral rather than subcutaneous AT has been shown to improve insulin sensitivity (Thörne et al. 2002). A crucial link between visceral obesity and insulin resistance is inflammation.
The relationship between inflammation and insulin-resistant states (obesity and diabetes) is well established. Obesity and T2DM, that is, diabesity, are associated with an increased risk of cardiovascular complications, for example, atherosclerosis, myocardial infarction, and stroke (De Flines and Scheen 2010). It has been reported that the proinflammatory cytokine TNF-α is increased in adipocytes of obese animals; the attenuation of TNF-α by soluble TNF-α receptor decreased insulin resistance in these animals (Hotamisligil et al. 1993). Furthermore, AT from obese individuals exhibits increased macrophage infiltration; these macrophages are a source of proinflammatory elements that have detrimental metabolic effects (Weisberg et al. 2003).
Section snippets
Omentin: the New Adipokine on the Block
Omentin/intelectin was initially described in intestinal Paneth cells; omentin/intelectin associates with galactofuranose within carbohydrate moieties of bacterial cell walls and has been implicated in the gut defensive mechanisms against pathogenic bacteria, for example, Escherichia coli (Komiya et al. 1998). In addition, a homolog of omentin/intelectin has been reported sharing 83% amino acid identity with omentin/intelectin designated as omentin 2. Omentin 1 is the major circulating form of
Omentin and Inflammation
Omentin messenger ribonucleic acid (mRNA) expression is decreased in omental AT of subjects with Crohn's disease (chronic inflammatory bowel disorder); this paucity of omentin may be important in the pathogenesis of transmural intestinal inflammation in these patients (Schäffler et al. 2005). Furthermore, omentin levels are decreased in synovial fluid of patients with rheumatoid arthritis (chronic inflammatory joint disorder) (Senolt et al. 2010).
Recently, we have reported that C-reactive
Omentin in Obesity, Diabetes, Insulin-Resistant, and Proinflammatory States
Circulating omentin and omentin gene expressions in visceral AT were reported to be decreased in obese subjects. In addition, circulating omentin levels were negatively correlated with markers of obesity, that is, body mass index, waist circumference, and circulating leptin; thus, obesity and, possibly, leptin may regulate omentin levels (De Souza Batista et al. 2007). In addition, given that obesity is associated with low levels of chronic inflammation, inflammatory factors may also regulate
Omentin and Cardiovascular Disease
Fain et al. (2008) has reported that omentin mRNA is mainly expressed in human epicardial and omental AT when compared with subcutaneous and internal mammary artery periadventitial AT depots; epicardial AT shares a common embryological origin with mesenteric and omental AT. Omentin, like other periadventitial epicardial adipokines, may play an important role in the pathogenesis of coronary vascular disease, in particular, coronary atherosclerosis, given that there is no fibrous fascial layer to
Conclusions
At present, it is not entirely clear as to how omentin fits into the homeostatic mechanisms that modulate the various functions of the human body in both health and disease, in particular, with respect to the metabolic syndrome and its associated complications. Given that omentin is expressed in the heart, lung, ovary as well as the placenta, the potential actions of omentin in these organ systems have yet to be delineated. The current lack of a definitive receptor for omentin and an
Acknowledgments
The General Charities of the City of Coventry
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