Increased Circulating and Visceral Adipose Tissue Expression Levels of YKL-40 in Obesity-Associated Type 2 Diabetes Are Related to Inflammation: Impact of Conventional Weight Loss and Gastric Bypass

Abstract

Plasma YKL-40 is elevated in patients with type 2 diabetes. The potential role of visceral adipose tissue (VAT) as a significant source of YKL-40 is unknown. In the study circulating and expression levels of YKL-40 were examined in VAT analyzing the contribution of adipocytes and stromovascular fraction cells (SVFCs). We also explored YKL-40's implication in insulin resistance and inflammation and the effect of weight loss on plasma YKL-40 concentrations. Samples obtained from 53 subjects were used in the study. Gene and protein expression levels of YKL-40 were analyzed in VAT as well as in both adipocytes and SVFCs. In addition, circulating YKL-40 concentrations were measured before and after weight loss achieved either by Roux-en-Y gastric bypass (n = 26) or after a conventional dietetic program (n = 20). Circulating concentrations and VAT expression of YKL-40 were increased in obese patients with type 2 diabetes (P < 0.01) as well as associated with variables of insulin resistance and inflammation. No differences in YKL-40 expression levels between adipocytes and SVFCs were detected. Monocyte chemoattractant protein-1 and homeostasis model assessment emerged (P < 0.01) as independent factors predicting circulating YKL-40. Elevated levels of YKL-40 in obese patients decreased after weight loss following a conventional hypocaloric diet (P < 0.05) but not via a surgery-induced negative energy balance mediated by the Roux-en-Y gastric bypass. The association of increased YKL-40 mRNA and protein levels in VAT with its circulating concentrations indicates an important contribution of VAT in YKL-40 regulation. Furthermore, our data suggest a relevant role of glucose metabolism and inflammation on YKL-40 regulation.