ZAG and a potential role in systemic lipid homeostastis: examining the evidence from in vitro human studies and patients with chronic illness

TY - JOUR

T1 - ZAG and a potential role in systemic lipid homeostastis: examining the evidence from in vitro human studies and patients with chronic illness

AU - McDermott, Lindsay

AU - Jadoon, Ayesha

AU - Cunningham, Phil

PY - 2012/8

Y1 - 2012/8

N2 - ZAG, a 42 kDa ubiquitously expressed soluble and secreted protein, consists of an MHC-like fold and binds fatty acids with an affinity similar to that of albumin. In human adipocytes, cytoplasmic and secreted ZAG appear inversely related to fat mass. Immunoblotting and biochemical measurements of human cachectic adipocytes and plasma suggest that ZAG's lipolytic function may be mediated by beta IAR. Plasma ZAG correlates with cholesterol in human populations, as does its single nucleotide polymorphism rs4215, which also associates with obesity. Biochemical and human genetic data, in vitro experiments and theoretical data imply that adipocyte ZAG's expression is regulated by PPAR-gamma and glucocorticoids. Cell biological experiments and data from human tissue indicate that ZAG may induce fatty-acid oxidation in skeletal muscle. Overall, these findings suggest ZAG's participation in systemic lipid homeostasis. Understanding the molecular mechanisms behind ZAG's in vivo behavior potentially allows for rational drug design to control body fat mass.

AB - ZAG, a 42 kDa ubiquitously expressed soluble and secreted protein, consists of an MHC-like fold and binds fatty acids with an affinity similar to that of albumin. In human adipocytes, cytoplasmic and secreted ZAG appear inversely related to fat mass. Immunoblotting and biochemical measurements of human cachectic adipocytes and plasma suggest that ZAG's lipolytic function may be mediated by beta IAR. Plasma ZAG correlates with cholesterol in human populations, as does its single nucleotide polymorphism rs4215, which also associates with obesity. Biochemical and human genetic data, in vitro experiments and theoretical data imply that adipocyte ZAG's expression is regulated by PPAR-gamma and glucocorticoids. Cell biological experiments and data from human tissue indicate that ZAG may induce fatty-acid oxidation in skeletal muscle. Overall, these findings suggest ZAG's participation in systemic lipid homeostasis. Understanding the molecular mechanisms behind ZAG's in vivo behavior potentially allows for rational drug design to control body fat mass.

U2 - 10.2217/CLP.12.45

DO - 10.2217/CLP.12.45

M3 - Literature review

SN - 1758-4299

VL - 7

SP - 409

EP - 417

JO - Clinical lipidology

JF - Clinical lipidology

IS - 4

ER -