Besides regulating fat distribution, GH also modifies the endocrine function of the adipose tissue [
102]. Adipokines participate in the regulation of energy balance, lipid and carbohydrate metabolism and inflammatory processes [
102,
103]. It is also suggested that the GH/IGF-1 axis can influence the secretion of adipokines, which, in turn, can mediate metabolic effects of the GH/IGF-1 axis [
102,
103]. The most frequently studied adipokines are leptin and adiponectin [
104]. Leptin, the first adipokine to be discovered, shows a positive correlation with fat mass and is likely associated with OS and vascular damage [
3,
105]. In GHD, some but not all studies reported higher levels of leptin [
85,
106] and a decrease in response to GHRT [
106,
107]. Adiponectin, the most abundant adipokine, is known for its antiatherogenic, insulin sensitizing and anti-inflammatory properties and has a key role in obesity-related diseases [
108,
109]. Fukuda et al demonstrated significantly lower adiponectin levels in GHD when compared to acromegalic patients, but no differences were found compared with adiponectin levels of normal subjects [
108]. Concerning the effect of GH substitution, elevated [
110] and unchanged [
111] adiponectin levels were also demonstrated in different trials. More recently, Wang et al. reported increased adipsin levels in GHD patients compared to controls, and found a significant correlation with cardiometabolic risk factors [
10]. Adipsin itself is found to improve and maintain pancreatic β-cell function and to increase insulin secretion to glucose [
112]. In obesity, higher adipsin production is considered a form of compensatory mechanism for normalizing lipid and glucose metabolism [
113]. This hypothesis may also explain the increased levels found in patients with AGHD.