Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action

Abstract

Central (visceral) obesity is more closely associated with insulin resistance, type 2 diabetes, and cardiovascular disease than is peripheral [subcutaneous (sc)] obesity, but the underlying mechanism for this pathophysiological difference is largely unknown. To understand the molecular basis of this difference, we sequenced 10,437 expressed sequence tags (ESTs) from a human omental fat cDNA library and discovered a novel visceral fat depot-specific secretory protein, which we have named omentin. Omentin ESTs were more abundant than many known adipose genes, such as perilipin, adiponectin, and leptin in the cDNA library. Protein sequence analysis indicated that omentin mRNA encodes a peptide of 313 amino acids, containing a secretory signal sequence and a fibrinogen-related domain. Northern analysis demonstrated that omentin mRNA was predominantly expressed in visceral adipose tissue and was barely detectable in sc fat depots in humans and rhesus monkeys. Quantative real-time PCR showed that omentin mRNA was expressed in stromal vascular cells, but not fat cells, isolated from omental adipose tissue, with >150-fold less in sc cell fractions. Accordingly, omentin protein was secreted into the culture medium of omental, but not sc, fat explants. Omentin was detectable in human serum by Western blot analysis. Addition of recombinant omentin in vitro did not affect basal but enhanced insulin-stimulated glucose uptake in both sc (47%, n = 9, P = 0.003) and omental (∼30%, n = 3, P < 0.05) human adipocytes. Omentin increased Akt phosphorylation in the absence and presence of insulin. In conclusion, omentin is a new adipokine that is expressed in omental adipose tissue in humans and may regulate insulin action.

Omentin-1, visfatin and adiponectin levels in relation to bone mineral density in Iranian postmenopausal women

“…Omentin-1 is a newly identified depot-specific adipokine in human adipose tissue that may modulate insulin sensitivity by its paracrine or endocrine functions [13].It was shown that omentin-1 levels were inversely correlated with measures of obesity and insulin resistance and positively correlated with adiponectin levels [15]. It was also reported that omentin-1 levels were lower in patients with metabolic syndrome than in controls [23].…”

“…Omentin-1 is a novel 34 kDa adipocytokine, which in comparison with subcutaneous adipose tissue, is highly and selectively expressed in visceral adipose tissue [12,13]. Furthermore, omentin-1 enhances insulin action and Akt phosphorylation [14]; it is inversely related to obesity [15] and is down regulated by insulin and glucose [13].…”

“…Furthermore, omentin-1 enhances insulin action and Akt phosphorylation [14]; it is inversely related to obesity [15] and is down regulated by insulin and glucose [13]. In an in vitro study to investigate the effects of omentin-1 on bone metabolism, omentin-1 reduced osteoclast formation by stimulating OPG and inhibiting RANKL production in osteoblasts [16].…”

Association of a fat-derived plasma protein omentin with carotid artery intima-media thickness in apparently healthy men

“…[1][2][3] Omentin, also known as intelectin-1, is a recently identified adipocytokine, whose expression is abundantly detected in human visceral fat tissue. [4][5][6] Omentin is detectable in human plasma and is downregulated in subjects with obesity and type 2 diabetes. 7,8 Low levels of plasma omentin are also associated with insulin resistance and endothelial dysfunction.…”

Common variants of SLAMF1 and ITLN1 on 1q21 are associated with type 2 diabetes in Indian population

“…ITLN1 encodes Intelectin 1 (Omentin 1), an adipokine that enhances insulin-stimulated glucose uptake in adipocytes. 32 Plasma levels of Intelectin 1 are inversely correlated with BMI, waist circumference and insulin resistance. 33 A study that investigated association of Val109Asp variant of ITLN1 with type 2 diabetes in Caucasians failed to detect the same.…”