Abstract
ObjectiveZinc-α2 glycoprotein (ZAG) stimulates lipid loss by adipocytes and may be involved in the regulation of adipose tissue metabolism. However, to date no studies have been made in the most extreme of obesity. The aims of this study are to analyze ZAG expression levels in adipose tissue from morbidly obese patients, and their relationship with lipogenic and lipolytic genes and with insulin resistance (IR).MethodsmRNA expression levels of PPARγ, IRS-1, IRS-2, lipogenic and lipolytic genes and ZAG were quantified in visceral (VAT) and subcutaneous adipose tissue (SAT) of 25 nondiabetic morbidly obese patients, 11 with low IR and 14 with high IR. Plasma ZAG was also analyzed.ResultsThe morbidly obese patients with low IR had a higher VAT ZAG expression as compared with the patients with high IR (p = 0.023). In the patients with low IR, the VAT ZAG expression was greater than that in SAT (p = 0.009). ZAG expression correlated between SAT and VAT (r = 0.709, p<0.001). VAT ZAG expression was mainly predicted by insulin, HOMA-IR, plasma adiponectin and expression of adiponectin and ACSS2. SAT ZAG expression was only predicted by expression of ATGL.Conclusions ZAG could be involved in modulating lipid metabolism in adipose tissue and is associated with insulin resistance. These findings suggest that ZAG may be a useful target in obesity and related disorders, such as diabetes.
Highlights
Obesity has been considered to be associated with a proinflammatory state, generating an increased incidence of dyslipidemia and insulin resistance (IR) [1]
Serum Zinc-a2 glycoprotein (ZAG) was similar between the two groups of morbidly obese patients
We show that visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) ZAG expression and its relation with the insulin resistance is different
Summary
Obesity has been considered to be associated with a proinflammatory state, generating an increased incidence of dyslipidemia and insulin resistance (IR) [1]. This association seems to be mediated by the release of various proinflammatory adipokines and cytokines (e.g., leptin, adiponectin, TNF alpha, IL6) by adipose tissue [2,3,4]. These proteins act either in an autocrine/paracrine/endocrine manner to locally regulate the adipocyte metabolism or as endocrine signals. ZAG overexpression in HFD-fed obese mice results in a reduction of body weight, epididymal fat mass and percentage of epididymal fat [14]
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