We have no satisfactory explanation for these discrepancies but we are aware that the study design does not allow us to draw valid conclusions in this regard. One of the main functions of ZAG is linked to lipid homeostasis. Experimental data indicate that this protein stimulates glycerol release and induces lipolytic activity in adipose tissue [32]. Administration of ZAG in ob/ob mice induces a reduction in fat mass with an increase in adipose tissue expression of hormone-sensitive lipase (HSL) and adipose triglyceride lipase

(ATGL). This Sirolimus ic50 is paralleled by a reduction in TG plasma levels with an increase in glucose transporter (GLUT4) in both skeletal muscle and adipose tissue [33, 34]. Consistent

with these findings in mice, the main determinant of ZAG circulating level in the HIV-1-infected cohort was HDLc plasma level (especially in men, because in women the median HDLc value was higher), independent of the inflammatory or insulin-resistance state. Recently, Ibrutinib a metabolic link between the lipolytic activity of adipocytes and the rate of cellular cholesterol efflux to HDL has been described in mice adipocytes [35]. Thus, the strong observed association between ZAG and HDLc plasma levels may reflect the lipolytic activity of ZAG in adipose tissue in HIV-1-infected patients. Our study has some limitations. First, the cross-sectional nature of our design provides associations and not causality. Secondly, we defined lipodystrophy clinically. Because of the lack of objective measurements of body composition, we cannot discount the possibility that some patients in the nonlipodystrophy subset could have had some minor subclinical changes that were not clinically detectable. However, we believe Lepirudin that this is unlikely because the study cohort

consisted of patients with extreme phenotypes. Thirdly, the uninfected control group consisted of hospital personnel. This may have introduced bias in several ways, such as biases related to diet and lifestyle, which may have affected the internal validity of the study. An additional bias in our data may have been introduced by the fact that controls were older and had a higher BMI than HIV-1-infected patients. Both age [36] and BMI [9, 11] have been shown to influence ZAG level, although data are inconsistent [9, 10]. Finally, we acknowledge that the results provided here are preliminary and that further studies are needed to replicate our data. In conclusion, HIV-1-infected patients were found to have lower plasma ZAG levels than UCs. These changes were mainly dependent on HDLc, but were also associated with total cholesterol, inflammatory markers and insulin.