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). The soluble glycoprotein has a molecular weight of 42 kDa. It was first identified in human plasma in association with cachectic states. The ZAG structure is similar to that of class I major histocompatibility complex (MHC) molecules, with a groove for binding fatty acids.
ZAG is expressed and secreted by various cells throughout the body, including keratinocytes and adipocytes. In adipose tissue, its expression is inversely related to body fat mass and influenced by diet, suggesting a link with obesity. ZAG expression in adipocytes is regulated through the PPAR-γ receptor, and modulated downward by TNF-α and upward by glucocorticoids. ZAG has recently emerged as an adipokine involved in lipid mobilization. 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. Increasing the level of cAMP activates hormone sensitive lipase (HSL) that catalyzes the hydrolysis of triglycerides into fatty acids and glycerol (see Figure 1).
ZAG may also indirectly modulate lipid metabolism via the stimulation of adiponectin and inhibition of leptin secretion by adipocytes. In addition, it is increasingly being viewed as a potential target for lipid homeostasis. 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.
Shea Butter Extract Preparation
In searching for a modulator of the ZAG protein, the authors evaluated the related potential of a new original shea butter (SB) extract obtained in a way that bypasses the traditional roasting step. Briefly, shea nuts are mechanically ground and hydrated to obtain a paste that is deeply churned to separate the water from the oil composing the butter. By avoiding high temperatures, this approach is a more sustainable manufacturing process and it supports better working conditions for the women of Burkina Faso in western Africa, who harvest the nuts to produce the extract. It also protects natural wood reserves that are otherwise burned in the process.
Interestingly, this process also was found to preserve viminalol content in the nuts. Viminalol is a triterpene that is normally degraded by heat during the roasting step. The presence of viminalol esters has previously been linked to anti-inflammatory and antioxidant activities. Thus, the viminalol esters were concentrated, and their quantity was standardized for this extract. Here, the authors assess the additional role of the esters in modulating ZAG protein expression in vitro. Further, to complete and reinforce the action of the unroasted SB extract, a complex was created including avocado seed extract and bentonite. Also harvested in Burkina Faso, the avocado seed extract is rich in unsaponifiable matter that is capable of supporting healthy connective tissue metabolism and providing anti-inflammatory action. Bentonite is a clay mineral valued for its regenerative and wound-healing properties, and its highly organized structure makes it an ideal carrier for other ingredients. The avocado seed extract and the SB extract were incorporated and entrapped in the bentonite to form a multilayer powder. This complex was used in the clinical studies described.