As a name, ZAG may sound more appropriate for a pop star rather than a protein but it reflects two properties of the molecule: the protein precipitates in the presence of zinc and moves like α2-microglobulins within an electrophoretic field. Hence, it is named zinc-α2-glycoprotein (ZAG).1 The soluble glycoprotein has a molecular weight of 42 kDa. It was first identified in human plasma in association with cachectic states.2 The ZAG structure is similar to that of class I major histocompatibility complex (MHC) molecules, with a groove for binding fatty acids.3
ZAG is expressed and secreted by various cells throughout the body, including keratinocytes and adipocytes.4, 5 In adipose tissue, its expression is inversely related to body fat mass and influenced by diet, suggesting a link with obesity.6 ZAG expression in adipocytes is regulated through the PPAR-γ receptor, and modulated downward by TNF-α and upward by glucocorticoids.4, 7, 8 ZAG has recently emerged as an adipokine involved in lipid mobilization.1, 9 It directly modulates lipid metabolism via β-3- and β-2(or β-1)-adrenergic receptors in rodents and humans, respectively, leading to activation of a cAMP-dependant pathway.1, 10 Increasing the level of cAMP activates hormone sensitive lipase (HSL) that catalyzes the hydrolysis of triglycerides into fatty acids and glycerol (see Figure 1).11
ZAG may also indirectly modulate lipid metabolism via the stimulation of adiponectin and inhibition of leptin secretion by adipocytes.9 In addition, it is increasingly being viewed as a potential target for lipid homeostasis.12 Therefore, the aim of the present study was to identify and test an extract to modulate ZAG protein expression in vitro, and to document the clinical effects of a complex containing that extract on the appearance of cellulite in humans.